comprehensive organic functional group transformations ii: v. 6(carbon with three or four attached...
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COMPREHENSIVE ORGANIC FUNCTIONAL GROUP TRANSFORMATIONS IIEditors-in-Chief: A.R. Katritzky, University of Florida, Gainesville, USAR.J.K. Taylor, Department of Chemistry, University of York, UK
Volumes 1-7 - 7-Volume Set
2004Imprint: ELSEVIER
Hardbound, ISBN: 0-08-044256-0, 6788 pages, publication date:
Description Comprehensive Organic Functional Group Transformations II (COFGT-II) will provide the first point of entry to the literature for all scientists interested in chemical transformations. Presenting the vast subject of organic synthesis in terms of the introduction and interconversion of all known functional groups, COFGT-II will provide a unique information source documenting all methods of efficiently performing a particular transformation. Organised by the functional group formed, COFGT-II will consist of 144 specialist reviews, written by leading scientists who will evaluate and summarise the methods available for each functional group transformation.
Volumes
Volume 1: Carbon with No Attached Heteroatoms
Volume 2: Carbon with One Heteroatom Attached by a Single Bond
Volume 3: Carbon with One Heteroatom Attached by a Multiple Bond
Volume 4: Carbon with Two Heteroatoms, Each Attached by a Single Bond
Volume 5: Carbon with Two Attached Heteroatoms with at Least One Carbon-to-Heteroatom Multiple Link
Volume 6: Carbon with Three or Four Attached Heteroatoms
Volume 7: Author Index and Cumulative Subject Index
Editors-in-Chief
Professor Alan R. Katritzky, FRSUniversity of Florida, Gainesville, FL, USA
Professor Richard J. K. TaylorUniversity of York, York, UK
Editors-in-Chief
Alan Katritzky, educated at Oxford, held faculty positions atCambridge and East Anglia before migrating in 1980 to theUniversity of Florida, where he is Kenan Professor and Directorof the Center for Heterocyclic Compounds. He has trained some800 graduate students and postdocs, and lectured and consultedworldwide. He led the team which produced ComprehensiveHeterocyclic Chemistry and its sequel CHECII, has edited Advancesin Heterocyclic Chemistry, Vols. 1 through 86 and conceived the planfor Comprehensive Organic Functional Group Transformations. Hefounded Arkat-USA, a nonprofit organization which publishesArchive for Organic Chemistry (ARKIVOC) electronic journalcompletely free to authors and readers at (www.arkat-usa.org).Honors include 11 honorary doctorates from eight countries andmembership or foreign membership of the National Academies ofBritain, Catalonia, India, Poland, Russia, and Slovenia.
Richard Taylor is currently Professor of Organic Chemistry at theUniversity of York, where his research focuses on the developmentof novel synthetic methodology and the synthesis of naturalproducts and related compounds of biological/medicinal interest.The methodology is concentrated primarily on organometallic,organosulfur, and oxidation processes, and the targets includeamino acids, carbohydrates, prostaglandins, and polyene andpolyoxygenated natural products, particularly with activity asantibiotics and anti-cancer agents.
Richard Taylor is a graduate and postgraduate of the Universityof Sheffield. After his studies at Sheffield, he carried out postdoctoralresearch at Syntex, California (Dr. I. T. Harrison) and UniversityCollege London (Professor F. Sondheimer). His first academicappointment was at the Open University in Milton Keynes. Thispost gave Professor Taylor the opportunity to contribute to OpenUniversity textbooks, radio programs and television productions on
various aspects of organic chemistry. Professor Taylor then moved to UEA, Norwich, where heestablished his independent research program, before taking up his present position in York in 1993.
Richard Taylor has just finished his term as President of the Organic Division of the Royal Societyof Chemistry and was awarded the 1999 RSC Tilden Lectureship and the 1999 RSC HeterocyclicPrize. He is currently the UK Regional Editor of the international journal Tetrahedron.
Volume Editors
EDITOR OF VOLUME 1
Janine Cossy did her undergraduate and graduate studies at theUniversity of Reims. After a postdoctoral stay with Barry Trost, fortwo years (1980–1982) at the University of Wisconsin, she returned toReims, where she became a Director of Research of the CNRS in1990. In the same year she moved to Paris to become Professor ofOrganic Chemistry at the ESPCI (Ecole Superieure de Physique etde Chimie Industrielles de la Ville de Paris). She is interested insynthetic methodologies (radicals, organometallics, photochemistry,thermal reactions, ring expansions, enantioselectivity, synthesis ofheterocycles, synthesis of solid support) and in their applications tothe synthesis of natural products and biologically active molecules.
EDITOR OF VOLUME 2
Chris Ramsden was born in Manchester, UK in 1946. He isa graduate of Sheffield University and received his Ph.D.(W. D. Ollis) in 1970 and D.Sc. in 1990. After postdoctoral workat the University of Texas (M. J. S. Dewar)(1971–1973) andUniversity of East Anglia (A. R. Katritzky)(1973–1976), he workedin the pharmaceutical industry. He moved to Keele University asProfessor of Organic Chemistry in 1992. His research interests areheterocycles and three-center bonds and applications of theirchemistry to biological problems.
EDITOR OF VOLUME 3
Keith Jones was born in Manchester. He studied at CambridgeUniversity for his B.A. in Natural Sciences (1976) and stayed tocarry out research with Professor Sir Alan Battersby obtaining hisPh.D. in 1979. In 1979, he moved to a lectureship at King’s CollegeLondon. In 1984, he caught up with his postdoctoral research byspending a year working with Professor Gilbert Stork at ColumbiaUniversity, New York. After returning to King’s College, hebecame a reader in 1995. In 1998, he moved to a chair in organicand medicinal chemistry at Kingston University. His researchinterests cover natural product synthesis, heterocyclic chemistryand the use of radicals in synthesis. He has been a visitingprofessor at Neuchatel and Barcelona Universities as well as theAustralian National University.
EDITOR OF VOLUME 4
Professor Gary Molander was born in Cedar Rapids, Iowa. Hereceived his B.S. degree at Iowa State University and subsequentlyentered the graduate chemistry program at Purdue University in1975, obtaining his Ph.D. degree in 1979 under the direction ofProfessor Herbert C. Brown. He joined Professor Barry Trost’sgroup at the University of Wisconsin, Madison 1980 as apostdoctoral research associate, and in 1981 he accepted anappointment at the University of Colorado, Boulder, as anAssistant Professor of chemistry, where he rose through theacademic ranks. In 1999 he joined the faculty at the University ofPennsylvania, and in 2001 was appointed Allan Day Professor ofChemistry. Professor Molander’s research interests focus on thedevelopment of new synthetic methods for organic synthesis andnatural product synthesis. A major focus of his research has beenthe application of organolanthanide reagents and catalysts toselective organic synthesis.
EDITOR OF VOLUME 5
Ray Jones started his chemistry career as an undergraduateand then completing a Ph.D. at Cambridge University under thesupervision of Professor Sir Alan Battersby, in the area of alkaloidbiosynthesis. After a year as an ICI Postdoctoral Fellow in thelaboratories of Professor Albert Eschenmoser at the ETH Zurich,he was appointed as Lecturer in Organic Chemistry at Universityof Nottingham in 1974. He progressed to Senior Lecturer atNottingham and then took up the Chair of Organic Chemistryat the Open University in 1995, before moving to the Chair ofOrganic and Biological Chemistry at Loughborough University in2000.
His research interests span heterocyclic and natural productchemistry, with over 100 publications. Example topics includethe acyltetramic acids and pyridones, Mammea coumarins, spermineand spermidine alkaloids, imidazolines as templates for (asymmetric)synthesis, dipolar cycloadditions, and unusual amino acids andpeptide mimetics.
EDITOR OF VOLUME 6
Eric F. V. Scriven is a native of Wales, UK. After working atBISRA and ESSO Ltd, he attended the University of Salford andgraduated in 1965. He obtained his M.Sc. from the University ofGuelph, and his Ph.D. from the University of East Anglia (withProfessor A. R. Katritzky) in 1969. After postdoctoral years at theUniversity of Alabama and University College London, he wasappointed Lecturer in organic chemistry at the University ofSalford. There, his research interests centered on the reactivity ofazides and nitrenes. While at Salford, he spent two semesters onsecondment at the University of Benin in Nigeria. He joined ReillyIndustries Inc. in 1979 and was director of Research from 1991to 2003. He is currently at the University of Florida. He editedAzides & Nitrenes (1984), and he and Professor H. Suschitzky werefounding editors of Progress in Heterocyclic Chemistry, which hasbeen published annually since 1989 by the International Society ofHeterocyclic Chemistry. He also collaborated with Professors
A. R. Katritzky and C. W. Rees as Editors-in-Chief of Comprehensive Heterocyclic Chemistry II(1997). His current research interests are in novel nitration reactions, ionic liquids, andapplications of polymers in organic synthesis.
Preface
Comprehensive Organic Functional Group Transformations (COFGT 1995) presented the vastsubject of organic synthesis in terms of the introduction and interconversion of functional groups,according to a rigorous system, designed to cover all known and as yet unknown functionalgroups.
Comprehensive Organic Functional Group Transformations II (COFGT-II), designed for specia-list and nonspecialist chemists, active in academic, industrial, and government laboratories, nowupdates the developments of functional group transformations since the publication of theCOFGT 1995. COFGT-II is structured in precisely the same manner as the original COFGTwork, allowing truly comprehensive coverage of all organic functional group transformations.
COFGT-II, in combination with COFGT 1995, provides an essential reference source for theall-important topic of methodologies for the interconversion of functional groups in organiccompounds, and provides an efficient first point of entry into the key literature and backgroundmaterial for those planning any research involving the synthesis of new organic compounds. Withthe increase in our understanding of the way in which the chemical structure of compoundsdetermines all physical, chemical, biological, and technological properties, targeted synthesisbecomes ever more important. The making of compounds is germane not only to organicchemistry but also to future developments in all biological, medical, and materials sciences.
The availability of the work in electronic format through ScienceDirect will greatly enhance itsutility.
The Editors-in-Chief would like to extend their warm thanks to the Volume Editors, thechapter authors, and the Elsevier staff for operating in such an efficient and professional manner.
A. R. KatritzkyR. J. K. Taylor
Introduction to Volume 6
Volume 6 is in four parts. Part I deals with tetracoordinate carbons bearing three heteroatoms.Part II covers tetracoordinate compounds bearing four heteroatoms, i.e., substituted methanes,and Part III deals with tricoordinate systems bearing three heteroatoms, i.e., where one hetero-atom is attached to a double bond. Part IV is brief and deals with stabilized radicals, carbocations,and carbanions. Volume 6 covers a very broad area of chemistry and, even at the time of writingthis second edition, many gaps in the development of organic chemistry still exist.
The organization within the three parts not only follows the same broad logic developed in theprevious volumes, but also has a structure unique to the multiheteroatom volume. According tothe Latest Placement Principle, CF3C(NR2)3 appears in the chapter dealing with the carbonsbearing three nitrogens (Chapter 6.5), not that dealing with carbons bearing three halogens(Chapter 6.1), while (CF3CH2O)2CO appears in Part III, not in Part I.
In the chapter dealing with the iminocarbonyl function in Part III, the substituents on nitrogenare discussed in each appropriate subsection in the order outlined above.Thus, the RN=groupwould be first considered with R=H, then alkyl, alkenyl, aryl and hetaryl, alkynyl, and thenheteroatom substituents in the usual order.
Each chapter is divided into sections and subsections which follow the same numbering systemthat was used for the first edition. Where no significant new work has appeared in a specific areasince the publication the first edition of Comprehensive Organic Functional Group Transformationsin 1995, this is stated. This should allow readers to judge readily the scope and intensity of workoutside their immediate area of expertise. Many growth areas are discussed, for example, theincrease in the number and variety of methods for the introduction of a trifluoromethyl groupinto aromatic and aliphatic molecules (Chapter 6.1). Another instance is a metathesis reactionthat involves the reaction of a metal or metalloid halide with a trimethyllithiomethane derivativesuch as (Me3Si)3CLi that promises general application for the synthesis of methanes that bear upto four metal or metalloid functions, many examples of which have yet to be made (Chapter 6.13).
E. F. V. ScrivenFlorida, USA
Explanation of the referencesystem
Throughout this work, references are designated by a number-lettering coding of which the firstfour numbers denote the year of publication, the next one to three letters denote the journal, andthe final numbers denote the page. This code appears in the text each time a reference is quoted.This system has been used successfully in previous publications and enables the reader to godirectly to the literature reference cited, without first having to consult the bibliography at the endof each chapter.
The following additional notes apply:1. A list of journal codes in alphabetical order, together with the journals to which they refer
is given immediately following these notes. Journal names are abbreviated throughoutusing the CASSI ‘‘Chemical Abstracts Service Source Index’’ system.
2. The references cited in each chapter are given at the end of the individual chapters.3. The list of references is arranged in order of (a) year, (b) journal in alphabetical order
of journal code, (c) part letter or number if relevant, (d) volume number if relevant, and(e) page number.
4. In the reference list the code is followed by (a) the complete literature citation in theconventional manner and (b) the number(s) of the page(s) on which the reference appears,whether in the text or in tables, schemes, etc.
5. For non-twentieth-century references, the year is given in full in the code.6. For journals which are published in separate parts, the part letter or number is given (when
necessary) in parentheses immediately after the journal code letters.7. Journal volume numbers are not included in the code numbers unless more than one
volume was published in the year in question, in which case the volume number is includedin parentheses immediately after the journal code letters.
8. Patents are assigned appropriate three-letter codes.9. Frequently cited books are assigned codes.
10. Less common journals and books are given the code ‘‘MI’’ for miscellaneous with thewhole code for books prefixed by the letter ‘‘B-’’.
11. Where journals have changed names, the same code is used throughout, e.g., CB refers toboth Chem. Ber. and to Ber. Dtsch. Chem. Ges.
JOURNAL ABBREVIATIONS
AAC Antimicrob. Agents Chemother.ABC Agric. Biol. Chem.AC Appl. Catal.ACA Aldrichim. ActaAC(P) Ann. Chim. (Paris)AC(R) Ann. Chim. (Rome)ACH Acta Chim. Acad. Sci. Hung.ACR Acc. Chem. Res.ACS Acta Chem. Scand.ACS(A) Acta Chem. Scand., Ser. AACS(B) Acta Chem. Scand., Ser. BAF Arzneim.-Forsch.AFC Adv. Fluorine Chem.AG Angew. Chem.AG(E) Angew. Chem., Int. Ed. Engl.AHC Adv. Heterocycl. Chem.AHCS Adv. Heterocycl. Chem. SupplementAI Anal. Instrum.AJC Aust. J. Chem.AK Ark. KemiAKZ Arm. Khim. Zh.AM Adv. Mater. (Weinheim, Ger.)AMLS Adv. Mol. Spectrosc.AMS Adv. Mass Spectrom.ANC Anal. Chem.ANL Acad. Naz. LinceiANY Ann. N. Y. Acad. Sci.AOC Adv. Organomet. Chem.AP Arch. Pharm. (Weinheim, Ger.)APO Adv. Phys. Org. Chem.APOC Appl. Organomet. Chem.APS Adv. Polym. Sci.AQ An. Quim.AR Annu. Rep. Prog. Chem.AR(A) Annu. Rep. Prog. Chem., Sect. AAR(B) Annu. Rep. Prog. Chem., Sect. BARP Annu. Rev. Phys. Chem.ASI Acta Chim. Sin. Engl. Ed.ASIN Acta Chim. Sin.AX Acta Crystallogr.AX(A) Acta Crystallogr., Part AAX(B) Acta Crystallogr., Part BB BiochemistryBAP Bull. Acad. Pol. Sci., Ser. Sci. Chim.BAU Bull. Acad. Sci. USSR, Div. Chem. Sci.BBA Biochim. Biophys. ActaBBR Biochem. Biophys. Res. Commun.BCJ Bull. Chem. Soc. Jpn.BEP Belg. Pat.BJ Biochem. J.BJP Br. J. Pharmacol.BMC Biorg. Med. Chem.BMCL Biorg. Med. Chem. Lett.BOC Bioorg. Chem.BP Biochem. Biopharmacol.BPJ Br. Polym. J.BRP Br. Pat.BSB Bull. Soc. Chim. Belg.BSF Bull. Soc. Chim. Fr.BSF(2) Bull. Soc. Chim. Fr., Part 2BSM Best Synthetic MethodsC ChimiaCA Chem. Abstr.CAN CancerCAR Carbohydr. Res.CAT Chim. Acta Turc.CB Chem. Ber.CBR Chem. Br.CC J. Chem. Soc., Chem. Commun.CCA Croat. Chem. ActaCCC Collect. Czech. Chem. Commun.CCHT Comb. Chem. High T. Scr.CCR Coord. Chem. Rev.CE Chem. ExpressCEJ Chem. -Eur. J.CEN Chem. Eng. NewsCHE Chem. Heterocycl. Compd. (Engl. Transl.)CHECI Comp. Heterocycl. Chem., 1st edn.CHECII Comp. Heterocycl. Chem., 2nd edn.CHIR ChiralityCI(L) Chem. Ind. (London)CI(M) Chem. Ind. (Milan)CJC Can. J. Chem.CJS Canadian J. Spectrosc.CL Chem. Lett.
CLY Chem. ListyCM Chem. Mater.CMC Comp. Med. Chem.COC Comp. Org. Chem.COFGT Comp. Org. Func. Group TransformationsCOMCI Comp. Organomet. Chem., 1st edn.CONAP Comp. Natural Products Chem.COS Comp. Org. Synth.CP Can. Pat.CPB Chem. Pharm. Bull.CPH Chem. Phys.CPL Chem. Phys. Lett.CR C.R. Hebd. Seances Acad. Sci.CR(A) C.R. Hebd. Seances Acad. Sci., Ser. ACR(B) C.R. Hebd. Seances Acad. Sci., Ser. BCR(C) C.R. Hebd. Seances Acad. Sci., Ser. C.CRAC Crit. Rev. Anal. Chem.CRV Chem. Rev.CS Chem. Scr.CSC Cryst. Struct. Commun.CSR Chem. Soc. Rev.CT Chem. Tech.CUOC Curr. Org. Chem.CZ Chem.-Ztg.CZP Czech. Pat.DIS Diss. Abstr.DIS(B) Diss. Abstr. Int. BDOK Dokl. Akad. Nauk SSSRDOKC Dokl. Chem. (Engl. Transl.)DP Dyes Pigm.E ExperientiaEC Educ. Chem.EF Energy FuelsEGP Ger. (East) Pat.EJI Eur. J. Inorg. Chem.EJM Eur. J. Med. Chem.EJO Eur. J. Org. Chem.EUP Eur. Pat.FCF Fortschr. Chem. Forsch.FCR Fluorine Chem. Rev.FES Farmaco Ed. Sci.FOR Fortschr. Chem. Org. Naturst.FRP Fr. Pat.G Gazz. Chim. Ital.GAK Gummi Asbest Kunstst.GC Green Chem.GEP Ger. Pat.GSM Gen. Synth. MethodsH HeterocyclesHAC Heteroatom Chem.HC Chem. Heterocycl. Compd. [Weissberger-Taylor series]HCA Helv. Chim. ActaHCO Heterocycl. Commun.HOU Methoden Org. Chem. (Houben-Weyl)HP Hydrocarbon ProcessIC Inorg. Chem.ICA Inorg. Chim. ActaIEC Ind. Eng. Chem. Res.IJ Isr. J. Chem.IJC Indian J. Chem.IJC(A) Indian J. Chem., Sect. AIJC(B) Indian J. Chem., Sect. BIJM Int. J. Mass Spectrom. Ion Phys.IJQ Int. J. Quantum Chem.IJS Int. J. Sulfur Chem.IJS(A) Int. J. Sulfur Chem., Part AIJS(B) Int. J. Sulfur Chem., Part BIS Inorg. Synth.IZV Izv. Akad. Nauk SSSR, Ser. Khim.JA J. Am. Chem. Soc.JAN J. Antibiot.JAP Jpn. Pat.JAP(K) Jpn. KokaiJBC J. Biol. Chem.JC J. Chromatogr.JCA J. Catal.JCC J. Coord. Chem.JCO J. Comb. Chem.JCE J. Chem. Ed.JCED J. Chem. Eng. DataJCI J. Chem. Inf. Comput. Sci.JCP J. Chem. Phys.JCPB J. Chim. Phys. Physico-Chim. Biol.JCR(M) J. Chem. Res. (M)JCR(S) J. Chem. Res. (S)
JCS J. Chem. Soc.JCS(A) J. Chem. Soc. (A)JCS(B) J. Chem. Soc. (B)JCS(C) J. Chem. Soc. (C)JCS(D) J. Chem. Soc., Dalton Trans.JCS(F1) J. Chem. Soc., Faraday Trans. 1JCS(F2) J. Chem. Soc., Faraday Trans. 2JCS(P1) J. Chem. Soc., Perkin Trans. 1JCS(P2) J. Chem. Soc., Perkin Trans. 2JCS(S2) J. Chem. Soc., (Suppl. 2)JEC J. Electroanal. Chem. Interfacial Electrochem.JEM J. Energ. Mater.JES J. Electron Spectrosc.JFA J. Sci. Food Agri.JFC J. Fluorine Chem.JGU J. Gen. Chem. USSR (Engl. Transl.)JHC J. Heterocycl. Chem.JIC J. Indian Chem. Soc.JINC J. Inorg. Nucl. Chem.JLC J. Liq. Chromatogr.JMAC J. Mater. Chem.JMAS J. Mater. Sci.JMC J. Med. Chem.JMOC J. Mol. Catal.JMR J. Magn. Reson.JMS J. Mol. Sci.JNP J. Nat. Prod.JOC J. Org. Chem.JOM J. Organomet. Chem.JOU J. Org. Chem. USSR (Engl. Transl.)JPC J. Phys. Chem.JPJ J. Pharm. Soc. Jpn.JPO J. Phys. Org. Chem.JPP J. Pharm. Pharmacol.JPR J. Prakt. Chem.JPS J. Pharm. Sci.JPS(A) J. Polym. Sci., Polym. Chem., Part AJPU J. Phys. Chem. USSR (Engl. Transl.)JSC J. Serbochem. Soc.JSP J. Mol. Spectrosc.JST J. Mol. Struct.K KristallografiyaKFZ Khim. Farm. Zh.KGS Khim. Geterotsikl. Soedin.KO Kirk-Othmer Encyc.KPS Khim. Prir. Soedin.L LangmuirLA Liebigs Ann. Chem.LC Liq. Cryst.LS Life. Sci.M Monatsh. Chem.MC Mendeleev CommunicationsMCLC Mol. Cryst. Liq. Cryst.MI Miscellaneous [journal or B-yyyyMI for book]MIP Miscellaneous Pat.MM MacromoleculesMP Mol. Phys.MRC Magn. Reson. Chem.MS Q. N. Porter and J. Baldas, ‘Mass Spectrometry of
Heterocyclic Compounds’, Wiley, New York, 1971N NaturwissenschaftenNAT NatureNEP Neth. Pat.NJC Nouv. J. Chim.NJC New J. Chem.NKK Nippon Kagaku Kaishi (J. Chem. Soc. Jpn.)NKZ Nippon Kagaku ZasshiNMR T. J. Batterham, ‘NMR Spectra of Simple Heterocycles’,
Wiley, New York, 1973NN Nucleosides & NucleotidesNZJ N. Z. J. Sci. Technol.OBC Organic and Biomolecular ChemistryOCS Organomet. Synth.OL Org. Lett.OM OrganometallicsOMR Org. Magn. Reson.OMS Org. Mass Spectrom.OPP Org. Prep. Proced. lnt.OPRD Org. Process Res. Dev.OR Org. React.OS Org. Synth.OSC Org. Synth., Coll. Vol.P PhytochemistryPA Polym. AgePAC Pure Appl. Chem.PAS Pol. Acad. Sci.
PB Polym. Bull.PC Personal CommunicationPCS Proc. Chem. Soc.PH ‘Photochemistry of Heterocyclic Compounds’, O.
Buchardt, Ed.; Wiley, New York, 1976PHA PharmaziPHC Prog. Heterocycl. Chem.PIA Proc. Indian Acad. Sci.PIA(A) Proc. Indian Acad. Sci., Sect. APJC Pol. J. Chem.PJS Pak. J. Sci. Ind. Res.PMH Phys. Methods Heterocycl. Chem.PNA Proc. Natl. Acad. Sci. USAPOL PolyhedronPP Polym. Prepr.PRS Proceed. Roy. Soc.PS Phosphorus Sulfur (formerly); Phosphorus Sulfur Silicon
(currently)QR Q. Rev., Chem. Soc.QRS Quart. Rep. Sulfur Chem.QSAR Quant. Struct. Act. Relat.RC Rubber Chem. Technol.RCB Russian Chemical Bull.RCC Rodd’s Chemistry of Carbon CompoundsRCM Rapid Commun. Mass Spectrom.RCP Rec. Chem. Prog.RCR Russ. Chem. Rev. (Engl. Transl.)RHA Rev. Heteroatom. Chem.RJ Rubber J.RJGC Russ. J. Gen. Chem. (Engl. Transl.)RJOC Russ. J. Org. Chem. (Engl. Transl.)RP Rev. Polarogr.RRC Rev. Roum. Chim.RS Ric. Sci.RTC Recl. Trav. Chim. Pays-BasRZC Rocz. Chem.S SynthesisSA Spectrochim. ActaSA(A) Spectrochim. Acta, Part ASAP S. Afr. Pat.SC Synth. Commun.SCI ScienceSH W. L. F. Armarego, ‘Stereochemistry of Heterocyclic
Compounds’, Wiley, New York, 1977, parts 1 and 2.SL SynlettSM Synth. Met.SR Sulfur ReportsSRC Supplements to Rodd’s Chemistry of Carbon CompoundsSRI Synth. React. Inorg. Metal-Org. Chem.SS Sch. Sci. Rev.SSR Second Supplements to Rodd’s Chemistry of Carbon Com-
poundsSST Org. Compd. Sulphur, Selenium, Tellurium [R. Soc.
Chem. series]SUL Sulfur LettersSZP Swiss Pat.T TetrahedronT(S) Tetrahedron, Suppl.TA Tetrahedron AsymmetryTAL TalantaTCA Theor. Chim. ActaTCC Top. Curr. Chem.TCM Tetrahedron, Comp. MethodTFS Trans. Faraday Soc.TH ThesisTL Tetrahedron Lett.TS Top. Stereochem.UK Usp. Khim.UKZ Ukr. Khim. Zh. (Russ. Ed.)UP Unpublished ResultsURP USSR Pat.USP U.S. Pat.WOP PCT Int. Appl. WO (World Intellectual Property
Organization Pat. Appl.)YGK Yuki Gosei Kagaku KyokaishiYZ Yakugaku ZasshiZAAC Z. Anorg. Allg. Chem.ZAK Zh. Anal. Khim.ZC Z. Chem.ZN Z. Naturforsch.ZN(A) Z. Naturforsch., Teil AZN(B) Z. Naturforsch., Teil BZOB Zh. Obshch. Khim.ZOR Zh. Org. Khim.ZPC Hoppe-Seyler’s Z. Physiol. Chem.ZPK Zh. Prikl. Khim.
List of Abbreviations
TECHNIQUES/CONDITIONS
18-C-6 18-crown-6))))) ultrasonic (sonochemistry)� heat, refluxAAS atomic absorption spectroscopyAES atomic emission spectroscopyAFM atomic force microscopyapprox. approximatelyaq. aqueousb.p. boiling pointCD circular dichroismCIDNP chemically induced dynamic nuclear polarizationCNDO complete neglect of differential overlapconc. concentratedCT charge transferee enantiomeric excessequiv. equivalent(s)ESR electron spin resonanceEXAFS extended X-ray absorption fine structureFVP flash vacuum pyrolysisg gaseousGC gas chromatographyGLC gas–liquid chromatographyh Planck’s constanth hourHOMO highest occupied molecular orbitalHPLC high-performance liquid chromatographyh� light (photochemistry)ICR ion cyclotron resonanceINDO incomplete neglect of differential overlapIR infraredl liquidLCAO linear combination of atomic orbitalsLUMO lowest unoccupied molecular orbitalMCD magnetic circular dichroismMD molecular dynamicsmin minute(s)MM molecular mechanicsMO molecular orbitalMOCVD metal organic chemical vapor depositionm.p. melting pointMS mass spectrometry
MW molecular weightNMR nuclear magnetic resonanceNQR nuclear quadrupole resonanceORD optical rotatory dispersionPE photoelectronppm parts per millionrt room temperatures solidSCF self-consistent fieldSET single electron transferSN1 first-order nucleophilic substitutionSN2 second-order nucleophilic substitutionSNi internal nucleophilic substitutionSTM scanning tunneling microscopyTLC thin-layer chromatographyUV ultravioletvol. volumewt. weight
REAGENTS, SOLVENTS, ETC.
Ac acetyl CH3CO-acac acetylacetonatoacam acetamideAcO acetateAcOH acetic acidAIBN 2,20-azobisisobutyronitrileAns ansylAr arylATP adenosine 50-triphosphate9-BBN 9-borabicyclo[3.3.1]nonyl9-BBN-H 9-borabicyclo[3.3.1]nonaneBEHP bis (2-ethylhexyl) phthalateBHT 2,6-di-t-butyl-4-methylphenol (butyrated hydroxytoluene)binap 2,20-bis(diphenylphosphino)-1,10-binaphthylbipy 2,20-bipyridylBn benzyl C6H5CH2- (NB avoid confusion with Bz)t-BOC t-butoxycarbonylbpy 2,20-bipyridylBSA N,O-bis(trimethylsilyl)acetamideBSTFA N,O-bis(trimethylsilyl)trifluoroacetamideBt benzotriazoleBTAF benzyltrimethylammonium fluorideBz benzoyl C6H5CO- (NB avoid confusion with Bn)Bzac benzoylacetoneCAN ceric ammonium nitrateCbz carbobenzoxychalcogens oxygen, sulfur, selenium, telluriumCH2Cl2 dichloromethaneCOD 1,5-cyclooctadieneCOT cyclooctatetraeneCp cyclopentadienylCp* pentamethylcyclopentadienyl18-crown-6 1,4,7,10,13,16-hexaoxacyclooctadecaneCSA camphorsulfonic acidCSI chlorosulfonyl isocyanateCTAB cetyl trimethyl ammonium bromideDABCO 1,4-diazabicyclo[2.2.2]octane
DBA dibenzylideneacetoneDBN 1,5-diazabicyclo[4.3.0]non-5-eneDBU 1,5-diazabicyclo[5.4.0]undec-5-eneDCC dicyclohexylcarbodiimideDDQ 2,3-dichloro-5,6-dicyano-1,4-benzoquinoneDEAC diethylaluminum chlorideDEAD diethyl azodicarboxylateDET diethyl tartrate (þ or �)DHP dihydropyranDIBAL-H diisobutylaluminum hydridediglyme diethylene glycol dimethyl etherdimsyl Na sodium methylsulfinylmethideDIOP 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butaneDIPT diisopropyl tartrate (þ or �)DMA dimethylacetamideDMAC dimethylaluminium chlorideDMAD dimethyl acetylenedicarboxylateDMAP 4-dimethylaminopyridineDME dimethoxyethaneDMF dimethylformamideDMI N,N0-dimethylimidazolidinoneDMN diaminomaleonitrileDMSO dimethyl sulfoxideDMTSF dimethyl(methylthio)sulfonium fluoroborateDPPB 1,2-bis(diphenylphosphino)butaneDPPE 1,2-bis(diphenylphosphino)ethaneDPPF 1,10-bis(diphenylphosphino)ferroceneDPPP 1,2-bis(diphenylphosphino)propaneEþ electrophileEADC ethylaluminium dichlorideEDG electron-donating groupEDTA ethylenediaminetetraacetateEEDQ N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinolineEt ethylEt2O diethyl etherEtOH ethanolEtOAc ethyl acetateEWG electron-withdrawing groupHMPA hexamethyl phosphoramideHMPT hexamethylphosphoric triamideIpcBH2 isopinocampheylboraneIpc2BH diisopinocampheylboraneKAPA potassium 3-aminopropylamideK-selectride potassium tri-s-butylborohydrideLAH lithium aluminium hydrideLDA lithium diisopropylamideLICA lithium isopropyl cyclohexylamideLITMP lithium tetramethyl piperidideL-selectride lithium tri-s-butyl borohydrideLTA lead tetraacetateMAO monoamine oxidaseMCPBA 3-chloroperoxybenzoic acidMCT mercury cadmium tellurideMe methylMEM methoxyethoxymethylMEM-Cl methoxyethoxymethyl chlorideMeOH methanolMMA methyl methacrylateMMC methylmagnesium carbonateMOM methoxymethyl
Ms methanesulfonyl (mesylate)MSA methanesulfonic acidMsCl methanesulfonyl chlorideMVK methyl vinyl ketoneNBS N-bromosuccinimideNCS N-chlorosuccinimideNMO N-methylmorpholine N-oxideNMP N-methyl-2-pyrrolidoneNu� nucleophilePPA polyphosphoric acidPCC pyridinium chlorochromatePDC pyridinium dichromatePh phenylphen 1,10-phenanthrolinePhth phthaloylPPE polyphosphate esterPPO 2,5-diphenyloxazolePPTS pyridinium p-toluenesulfonatePr propylPyr pyridineRed-Al sodium bis(methoxyethoxy)aluminum dihydrideSDS sodium dodecyl sulfateSEM trimethylsilylethoxymethylSia2BH disiamylboraneSM starting materialTAS tris(diethylamino)sulfoniumTBAF tetra-n-butylammonium fluorideTBDMS t-butyldimethylsilylTBDMS-Cl t-butyldimethylsilyl chlorideTBDPS t-butyldiphenylsilylTBHP t-butyl hydroperoxideTCE 2,2,2-trichloroethanolTCNE tetracyanoethyleneTEA tetraethylammoniumTES triethylsilylTf triflyl (trifluoromethanesulfonyl)TFA trifluoroacetylTFAA trifluoroacetic anhydrideTHF tetrahydrofuranTHP tetrahydropyranylTIPBSCl 2,4,6-triisopropylbenzenesulfonyl chlorideTIPSCl triisopropylsilyl chlorideTMEDA tetramethylethylenediamine [1,2-bis(dimethylamino)ethane]TMS trimethylsilylTMSCl trimethylsilyl chlorideTMSCN trimethylsilyl cyanideTol tolyl C6H4(CH3)–TosMIC tosylmethyl isocyanideTPP meso-tetraphenylporphyrinTr trityl (triphenylmethyl)Tris tris(hydroxymethyl)aminomethaneTs 4-toluenesulfonyl (tosyl)TTFA thallium trifluroacetateTTMSS tris(trimethylsilyl)silaneTTN thallium(III) nitrateX halogen or leaving group
Volume 6: Synthesis: Carbon With Three or Four Attached Heteroatoms
Part I: Tetracoordinated Carbon with Three Attached HeteroatomsRCX X X1 2 3
6.01 Trihalides, Pages 1-22, G. Sandford
6.02 Functions Containing Halogens and Any Other Elements, Pages 23-74, J. Suwi ski and K. Walczak
6.03 Functions Containing Three Chalcogens (and No Halogens), Pages 75-110, S. Rádl and S. Voltrová
6.04 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen, Pages 111-159, A. M. Shestopalov
6.05 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen), Pages 161-203, A. Güven
6.06 Functions Containing at Least One Metalloid (Si, Ge, or B) and No Halogen, Chalcogen, or Group 15 Elements; Also the Synthesis of Functions Containing Three Metals, Pages 205-242, V. D. Romanenko and V. L. Rudzevich
Part II: Tetracoordinated Carbon with Four Attached HeteroatomsCX X X X1 2 3 4
6.07 Functions Containing Four Halogens or Three Halogens and OneOther Heteroatom Substituent, Pages 243-269, A. Senning and J. Ø. Madsen
Pages 271-294, G. Varvounis and N. Karousis
Pages 295-305, S. V. Yarlagadda and R. Murugan6.10 Functions Containing Four or Three Chalcogens (and No Halogens),
Pages 307-315, A. Senning and J. O. Madsen6.11 Functions Containing Two or One Chalcogens (and No Halogens),
Pages 317-353, W. Petz and F. Weller
6.12 Functions Containing at Least One Group 15 Element (and No Halogenor Chalcogen), Pages 355-379, S. Saba and J. A. Ciaccio
6.13 Functions Containing at Least One Metalloid (Si, Ge, or B) and No
Pages 381-408, P. D. Lickiss
6.08 Functions Containing Two Halogens and Two Other Heteroatom Substituents,
6.09 Functions Containing One Halogen and Three Other Heteroatom Substituents,
Halogen, Chalcogen, or Group 15 Element; Also Functions Containing Four Metals,
ń
Part III: Tricoordinated Carbon with Three Attached Heteroatoms Y=CX X1 2
6.14 Functions Containing a Carbonyl Group and at Least One Halogen, Pages 409-427, R. Murugan and S. V. Yarlagadda
6.15 Functions Containing a Carbonyl Group and at Least One Chalcogen (but No Halogen), Pages 429-452, H. Eckert
6.16 Functions Containing a Carbonyl Group and Two Heteroatoms Other Than a Halogen or Chalcogen, Pages 453-493, O. V. Denisko
6.17 Functions Containing a Thiocarbonyl Group and at Least One Halogen; Also at Least One Chalcogen and No Halogen, Pages 495-544, E. Kleinpeter
6.18 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms Other Than a Halogen or Chalcogen,
6.19 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group—1)X2 and SeC(X 1)X2, Pages 573-594, L. J. Guziec and F. S. Guziec, Jr.
6.20 Functions Containing an Iminocarbonyl Group and at Least One Halogen; Also One Chalcogen and No Halogen, Pages 595-604, T. L. Gilchrist
6.21 Functions Containing an Iminocarbonyl Group and Any Elements Other Than a Halogen or Chalcogen, Pages 605-660, F. S czewski
6.22 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal, Pages 661-711, V. D. Romanenko and V. L. Rudzevich
6.23 Tricoordinated Stabilized Cations, Anions, and Radicals, +CX1X2X3, CX1X2X3 CX1X2X3, Pages 713-727, M. Balasubramanian
Pages 545-572, J. Barluenga, E. Rubio and M. Tomás
TeC(X
ą
, and- .
6.01
Trihalides
G. SANDFORD
University of Durham, Durham, UK
6.01.1 GENERAL METHODS 16.01.1.1 The Addition of Halogens and Interhalogens to Fluoroalkenes 26.01.1.2 The Addition of Haloalkanes to Haloalkenes 26.01.1.2.1 Lewis acid-catalyzed addition of trihalomethyl cations to haloalkenes—the Prins reaction 26.01.1.2.2 Additions initiated by free radicals, heat, or radiation 26.01.1.2.3 Additions catalyzed by salts and complexes of transition metals 4
6.01.2 TRIFLUOROMETHYL DERIVATIVES, R�CF3 56.01.2.1 General 56.01.2.2 Aryl Derivatives 56.01.2.2.1 Conversion of groups attached to an aromatic ring into the trifluoromethyl group 56.01.2.2.2 Substitution by trifluoromethyl radicals 66.01.2.2.3 Substitution of hydrogen by trifluoromethyl group acting as an electrophile 66.01.2.2.4 Substitution of halogens by trifluoromethyl group acting as a nucleophile 76.01.2.2.5 Substitution of halogen by trifluoromethyl group using derivatives of metals 7
6.01.2.3 Derivatives of Alkanes, Alkenes, Alkynes, and Other Unsaturated Compounds 86.01.2.3.1 Halogen exchange 86.01.2.3.2 Conversions of other groups to the trifluoromethyl group 96.01.2.3.3 Transfer of trifluoromethyl groups as radicals 106.01.2.3.4 Reactions involving trifluoromethyl derivatives of metals and metalloids 11
6.01.3 TRICHLOROMETHYL DERIVATIVES, R�CCl3 166.01.3.1 Trichloromethyl Groups Attached to an Aliphatic Center 166.01.3.1.1 Conversion of groups attached to an aliphatic center into the trichloromethyl group 166.01.3.1.2 Transfer of the trichloromethyl group to an aliphatic center 16
6.01.3.2 Trichloromethyl Groups Attached to an Aromatic Ring 176.01.3.2.1 Conversion of groups attached to an aromatic ring into a trichloromethyl group 176.01.3.2.2 Transfer of trichloromethyl group to an aromatic ring 17
6.01.4 TRIBROMOMETHYL DERIVATIVES, R�CBr3 176.01.5 MIXED SYSTEMS WITH FLUORINE, R�CF2Hal AND RCFHal2 186.01.6 MIXED HALOFORMS, CHXY2 AND CHXYZ 18
6.01.1 GENERAL METHODS
There are several general methods that may be used for the synthesis of trihalomethyl com-pounds, and these were discussed in detail in COFGT (1995) <1995COFGT(6)1>. The experi-mental basis behind these established procedures remains valid; so in this chapter, a briefoverview of addition reactions of halogens and haloalkenes to alkenes for the synthesis of systemsbearing trihalomethyl groups is provided. Recent developments and further applications of thesegeneral processes are given where appropriate.
1
6.01.1.1 The Addition of Halogens and Interhalogens to Fluoroalkenes
The addition of halogens and interhalogens to fluorinated alkenes is a well-established method forthe synthesis of compounds bearing CHal3 groups and this area has recently been summarized<2000MI331, 2000MI234>.
Many examples of such electrophilic addition processes, involving electrophilic halonium ionand nucleophilic fluoride ion, are given in COFGT (1995) and a few examples (Equations (1)–(3))are shown below as an illustration <1978JFC(12)257, 1973ZOR673, 1961JCS3779>.
HFHexachloromelamine
CH2=CCl2 CH2Cl CFCl2
33%
ð1Þ
Cl F, –10 °CCF2 CF CF3 CF3–CFCl–CF3100%ð2Þ
IF5, 2 I2
150 °CCF2 CF–CF3 CF3–CFI–CF3
99%
ð3Þ
6.01.1.2 The Addition of Haloalkanes to Haloalkenes
The addition of haloalkanes to alkenes, catalyzed by either Lewis acids, free radical initiators,salts, and transition metal complexes, may be used for the synthesis of systems that beartrihalomethyl substituents, following the general scheme shown in Equation (4).
CY3–X + CY3 X X = Hal or HY = Hal
ð4Þ
6.01.1.2.1 Lewis acid-catalyzed addition of trihalomethyl cationsto haloalkenes—the Prins reaction
Trihalomethylation of alkenes by Lewis acid-catalyzed condensation with a tetrahalomethane, anadaptation of the Prins reaction, has been known for many years <1977FCR39>. Representativeexamples <1974CCC1330, 1971CCC1867> to illustrate these processes are shown below(Equations (5) and (6)), although this methodology has undergone limited recent development.
F
F
F
H+ CFCl3
0 °C, 7 hF
CF3 CCl3
F
CF2Cl CFCl2+
(70:30)
65% ð5Þ
F
F
F
F+ CHFCl2
15 °C, 3 h
CF3 CHCl2 CF2Cl CHFCl+
(59:41)
F F F F
58% ð6Þ
6.01.1.2.2 Additions initiated by free radicals, heat, or radiation
Trihalomethyl radicals, generated by heat, peroxide, or UV initiation, react with alkenes to forman intermediate radical as shown below (Scheme 1). This radical may then react with furtherequivalent(s) of alkene to lead to oligomers and polymers or abstract a halogen atom from amolecule of the starting material to give a tetrahalogenated product.
2 Trihalides
The product distribution depends upon the relative rates of each of the stages outlined above.Generally, starting materials with weak carbon�halogen bonds (iodides) give predominantly low-molecular-weight products, whilst systems with relatively strong carbon�halogen bonds give ahigher proportion of oligomeric products. Furthermore, if the alkene is not easily polymerizedunder normal conditions (e.g., hexafluoropropene) the addition product is favored, while readilyhomopolymerized alkenes lead to polymeric systems. The addition of the halomethyl radicals isoften regioselective due to a combination of steric and electronic factors <1982AG(E)401,1996CRV1557, 1997TCC(192)97>.
Since the initial report by Kharasch <1947JA1100> describing such radical chain additionprocesses, a substantial literature has developed <1963OR91, B-1992MI002, B-1986MI001>,detailing the syntheses of a great number of free-radical addition adducts, oligomers, andpolymers all bearing trihalomethyl end groups. A selection of these processes is given below(Equations (7)–(11)) to illustrate some of the processes possible <1961JOC2089, 1955JA2783,1953JCS1592, 1964JOC1198, 1981TL3405>.
OH + CF3I hνF3C OH
I
50%ð7Þ
F + CBr2F2(PhCO)2O
100 °C F F
Br FBr
32%
ð8Þ
F
F
F
Cl
+ CF3Ihν
I
F
CF3
FFCl75%
ð9Þ
OEt + CBr2F2F OEt
Br Br
83%Fhν ð10Þ
CY3 X CY3 + X
Initiation
or RO–OR
hν or heat
RO CY3 X+ RO-X + CY3
Propagation
CY3 + Y3C
Y3C
Chain transfer
+ CY3–X Y3C X Kharasch addition product
Oligomerization
Y3C + n Y3Cn
Termination
Y3Cn
+ CY3–X Y3Cn
X oligomers (n = 2–20)polymers (n = >20)
2 RO
Scheme 1
Trihalides 3
N
+ CF2BrClrt
OCF2Cl
65%
H2O
ð11Þ
The addition processes outlined above all lead to the formation of tetrahaloalkane systems inwhich trihalomethyl and halogen are added across a double bond. These reactions have, however,recently been adapted for the synthesis of trichloromethyl derivatives by the addition of aneffective hydrogen atom donor (Equations (12) and (13)). Reaction of tetrachloromethane withalkenes in the presence of diethyl phosphite leads to good yields of trichloromethylated productsbecause hydrogen is transferred to the intermediate radical, rather than halogen abstractionoccurring <2001SL1719>.
C6H13 + CCl4(EtO)2P(O)H
(PhCO2)2C6H13
CCl3C6H13
Cl
CCl3+
(55%) (30%)
ð12Þ
OH+ CCl4
(EtO)2P(O)H
(PhCO2)2OHCCl3 OHCCl3+
(44%) (16%)
ð13Þ
This methodology has been adapted to allow free-radical tandem trichloromethylation/cyclizationprocesses (Equation (14)) which occur efficiently in the presence of diethyl phosphite<2001TL3137>.
NTos
CCl4, (EtO)2P(O)H
(PhCO2)2ODioxane
NTos
Cl3C
NTos
Cl3C
+
Cl
(60%) (4%)
ð14Þ
6.01.1.2.3 Additions catalyzed by salts and complexes of transition metals
The observation that thermally initiated addition processes involving reaction between carbontetrachloride and acrylonitrile could be affected by the presence of metals or metal salts to givegreater yields of the Kharasch addition product rather than oligomers prompted much research.Many different metals, metal salts, metal oxides, and transition metal complexes have beenassessed for their effectiveness in such addition processes and are listed in COFGT (1995).
Recently, Kharasch addition using ruthenium(II) complexes has been assessed <2000TL5347>and the process (Equation (15)) may be affected by changing the ligand on the ruthenium metalcenter <2000TL6071>.
O
OMe
+ CCl4RuCl(Cp*)(PPh3)2
40 °C
O
OMe
Cl3CCl
ð15Þ
Grubbs’ well-defined ruthenium catalyst, RuCl2(¼CHPh) (PR3)2 <1999JOC344>, and variousdiaminonickel (II) ‘‘pincer’’ complexes <1998ACR423> have also been used to promote bothaddition and polymerization reactions.
4 Trihalides
6.01.2 TRIFLUOROMETHYL DERIVATIVES, R�CF3
6.01.2.1 General
The growing number of life science products that bear trifluoromethyl groups provides a con-tinuing driving force for the development of effective methodology that enables both regio- andstereoselective introduction of trifluoromethyl groups into both aliphatic and aromatic systems.In more specific cases, the use of �-trifluoromethyl ketones as potent enzyme inhibitors<2001MI755> and the synthesis of aliphatic cyclic systems that bear trifluoromethyl groupshas been discussed <2000T3635>.
In general, trifluoromethylating reagents which transfer trifluoromethyl groups directly onto asubstrate by carbon�carbon bond formation may be considered as either electrophilic (CF3
+),radical (CF3_), or nucleophilic (CF3
�) trifluoromethylating systems. It is fair to say that in the1990s many of the major developments in this area of synthetic chemistry have occurred innucleophilic trifluoromethylation methodology, particularly in the use of Ruppert’s reagent,CF3SiMe3. This is reflected in the publication of major reviews detailing syntheses involvingRuppert’s reagent by Prakash <1997CRV757, 2001JFC(112)123> and Shreeve <2000T7613>,and more general nucleophilic trifluoromethylation by Langlois<2003S185>. Of course, functionalgroup interconversion, resulting in the transformation of substituents, already located on a sub-strate, into a trifluoromethyl group upon reaction with a fluorinating reagent (carbon�fluorine bondformation), is an alternative strategy.
6.01.2.2 Aryl Derivatives
6.01.2.2.1 Conversion of groups attached to an aromatic ring into the trifluoromethyl group
Reaction of trichloromethyl and carboxylic acid groups with fluorinating agents, as discussed inCOFGT (1995), continues to provide effective methodology for the synthesis of trifluoromethylaromatic derivatives. Recent adaptations of this methodology are outlined below.
Exchange of halogen for fluorine (Halex process) involving reaction of benzotrichloride deri-vatives with anhydrous hydrogen fluoride, antimony trifluoride, or hydrogen fluoride/antimonypentafluoride as fluorinating agents remains the most useful industrial process for the synthesis ofaromatic trifluoromethyl derivatives. A one-step Friedel Crafts/Halex process is particularlyefficient for the synthesis of various brominated <1981JFC(18)281> and acetanilide<2003TL1747> trifluoromethyl derivatives (Equations (16) and (17)).
Br
HF, CCl4
CF3
Br
CF3
Br
+ ð16Þ
N
Cl
H Ac
i. HF, CCl4 , SbF5
ii. HF.pyridine
N
Cl
H Ac
CF385%
ð17Þ
There are now many examples of the transformation of carboxylic acid groups into trifluoro-methyl groups using sulfur tetrafluoride, and this methodology continues to be used for thesynthesis of poly trifluoromethyl aromatic systems <1997JFC(82)163> (Equation (18)).
HO2CCO2H
CO2Hi. HF, SF4
ii. KOH
55%
F3CCO2H
CF3 ð18Þ
Trihalides 5
6.01.2.2.2 Substitution by trifluoromethyl radicals
Electrophilic trifluoromethyl radicals, generated by electrolysis of potassium trifluoromethanesulfinate(Equation (19)) may be trapped by electron-rich aromatic systems <2002SL1697> (Equation (20)).
CF3SO2–e–
CF3SO2–SO2
CF3ð19Þ
OMe
OMe
CF3SO2K, DMF
Et4NClO4
Electrolysis
OMe
OMe
CF3
32%
ð20Þ
6.01.2.2.3 Substitution of hydrogen by trifluoromethyl group acting as an electrophile
For electrophilic trifluoromethylating reagents, originally developed by Umemoto, the trifluoro-methyl group is made highly susceptible toward nucleophilic attack by being attached to a verygood leaving group, such as a sulfonium derivative (Equation (21)).
CF3 SR2Nuc Nuc CF3 + SR2
+ ð21Þ
Intramolecular cyclization of trifluoromethyl sulfoxides provides efficient methodology for thesynthesis of trifluoromethyl dibenzothiophenium salts (Equation (22)), which act as effectiveelectrophilic trifluoromethylating reagents that are now commercially available but expensive<1998JFC(92)181, 1999JFC(98)75>.
SO
CF3
60% SO3–H2SO4
SCF3
HSO4
NaOTf
MeCN SCF3
OTf92%
ð22Þ
Variation of the chalcogen (S, Se, Te) and aromatic ring substituents lead to a series of relatedsulfur, selenium, and tellurium (trifluoromethyl)dibenzo-phenium triflates that can act as ‘‘powervariable’’ trifluoromethylating reagents, in which the most powerful trifluoromethylating reagentsare based on sulfonium systems with highly electron-withdrawing groups attached to botharomatic rings <1995JFC(74)77>.
Electrophilic trifluoromethylation of anilines <1995JFC(74)77> (Equation (23)), for whichrelated kinetic studies have been performed <1996JFC(80)163>, and zinc porphyrins<1999EJO2471>, which leads to the synthesis of longer-wavelength absorbing meso-substitutedsystems (Equation (24)), has been reported using the Umemoto reagents.
NH2NH2
CF3
NH2
CF3
SCF3
SO3NO2
(37%) (18%)
+
+
ð23Þ
N N
NN
Zn
SCF3
O2N NO2 CF3SO3
THF
N N
NN
Zn CF3
16% + three other products
+
ð24Þ
6 Trihalides
New electrophilic trifluoromethylating reagents, based upon diaryl sulfides (Equation (25)),allow efficient trifluoromethylation of pyrroles <1998JOC2656>.
SCF3
O BenzeneTf2O
SCF3
OTfHNO3
SCF3
OTfNO2
NH
NH
CF3
80%
+ +
ð25Þ
6.01.2.2.4 Substitution of halogens by trifluoromethyl group acting as a nucleophile
Only aromatic systems that are highly activated toward nucleophilic attack may be trifluoro-methylated directly by nucleophilic aromatic substitution using trifluoromethyl anions generatedby reaction of fluoride ion with Ruppert’s reagent <1990IZV169> (Equation (26)).
TMS–CF3
TAS–FNF
FF
F
F NF
FCF3
F
F
ð26Þ
6.01.2.2.5 Substitution of halogen by trifluoromethyl group using derivatives of metals
Trifluoromethylcopper, which may be generated in situ by various methods <1986JA832> includ-ing from either trifluoromethyl iodide and copper or sodium trifluoroacetate and copper(I) iodide,acts as a source of trifluoromethyl anion for the replacement of bromine and iodine, activatedtoward nucleophilic attack by the presence of copper ions, attached to activated aromatic rings.Syntheses of trifluoromethyl retinoial analogs <1999JFC(96)159> (Equation (27)), aromatics<2002T121, 1999JFC(96)159> (Equation (28)), and pyridine derivatives <2002EJO327>(Equations (29) and (30)) have been reported recently using these reagent systems.
OMe
OMeBr
O Ph CF3COONa
CuI, DMF
OMe
OMeCF3
O Ph
84%
ð27Þ
Br
NO2
FSO2CF2CO2Me
CuI
CF3
NO285%
ð28Þ
N
Br
I
TMSCF3
KF, CuI N
Br
CF369%
ð29Þ
N Cl
TMSCF3
KF, CuI N Cl67%
I CF3
ð30Þ
Trihalides 7
6.01.2.3 Derivatives of Alkanes, Alkenes, Alkynes, and Other Unsaturated Compounds
Many of the reagents utilized for trifluoromethylation of aromatic systems have been applied tocorresponding trifluoromethylation of aliphatic derivatives at both sp2 and sp3 carbon sites.
6.01.2.3.1 Halogen exchange
Halogen exchange (halex) processes, involving nucleophilic substitution of halogen by fluorineusing a metal fluoride in combination with anhydrous hydrogen fluoride, continues to be veryimportant for the industrial production of small fluorinated hydrocarbons such as the chloro-fluorocarbons (CFCs) and hydrofluorocarbons (HFCs). Since the establishment of the MontrealProtocol, effectively banning the use of CFCs in developed countries, manufacturing processes forthe synthesis of HFCs have been rapidly implemented.
Metal fluoride-effected substitution processes proceed via carbocation intermediates, (Scheme 2),as explained more fully in COFGT (1995).
Representative examples of this established and very important methodology are reiteratedbelow for completeness (Equations (31) and (32)). Metal fluorides such as antimony pentafluorideand various chromia catalysts are most commonly used in conjunction with HF <1942JA3476,1960USP2921099>.
ClCCl3
SbF3, SbF3Cl2 ClCF3
80%ð31Þ
Cl
BrCl
BrH
Cl HF, SbF3 F3C Cl
BrH42%
ð32Þ
Fluorinated chromia aerogel materials <2003JFC(121)83> (Equation (33)), alumina andaluminum(III) fluoride <2001JFC(110)181, 2001JFC(107)45>, and chromia impregnated withzinc <1999GC9> act as heterogeneous catalysts for the isomerization of various CFCs.
CCl2F–CF2ClChromia catalyst
HeatCF3–CCl3 ð33Þ
The manufacture and current applications of HFCs and the current market situation regardingHFCs have been discussed <2001CI(M)83> and the process of phasing out CFCs has beenaddressed <2002JFC(114)237>.
Various halogen exchange processes have been performed in which most, or all, of the usualaprotic solvent medium, such as sulfolane, was replaced by a perfluoroalkane fluid. In some cases,the products obtained using sulfolane/perfluoroalkane media were different from those foundwhen using sulfolane alone. Hexachlorodiene, for example, gave hexafluorobut-2-yne, rather thanheptafluorobutene, as the major product (Equation (34)) when carried out in a perfluoroalkane-rich reaction medium because elimination of fluoride to give the alkyne occurs preferentially<1997JCS(P1)3623>.
ClCl
Cl
Cl
Cl
Cl
KF, 190 °C
Sulfolane, PFPHP CF3 CF3+
F
CF3
CF3
H
(75%) (25%)
Via carbanion:F
CF3
CF3
ð34Þ
C Cl + MFx C MFx–1ClHF
C For
CCl
FMFx–1
Scheme 2
8 Trihalides
6.01.2.3.2 Conversions of other groups to the trifluoromethyl group
Bromine trifluoride, prepared from fluorine and bromine, converts aliphatic nitriles to thecorresponding trifluoromethyl derivatives (Equation (35)) by a sequence of addition/eliminationprocesses <2001JFC(111)161>.
NC CO2EtBrF3
CF3 CO2Et
35%
ð35Þ
Fluorodesulfurization of unsaturated dithiolates (Equation (36)) mediated by sources of posi-tively charged halonium and negative fluoride ion, give rise to various trifluoromethyl alkenes<1996SL1199>.
Ar SEt
SNIS
Bu4NH2F3 ArCF3
65%
ð36Þ
Trifluoromethyl 1,3-diketone systems may be synthesized upon reaction of an electrophilictrifluoromethylation reagent with the corresponding carbanion precursor <1995JFC(74)77>,giving overall substitution of hydrogen by trifluoromethyl (Equation (37)).
O O
CH3
Na A, DMF O O
CH3 CF3
86% SCF3
SO3A = ð37Þ
Perfluorinated systems, that is, molecules in which all the hydrogen atoms have been replaced byfluorine, may be synthesized by a variety of techniques. Direct fluorination (Equations (38)–(40))permits the synthesis of perfluorinated systems from the parent hydrocarbons <1979MI161,1997TCC(193)1, 2003T437>. The concentration of fluorine and the reaction temperature are slowlyincreased over a period of several days to effect perfluorination, while minimizing substrate degrada-tion. Many perfluorinated systems bearing trifluoromethyl groups have been synthesized by thistechnique and some examples are given <1997TCC(193)1> (Equations (38)–(40)).
CF3CF3
CF3CF3
CF3CF3F F
F FF2, N2
89%ð38Þ
CH3
CH3
F F
CF3
CF3
F
F2, N2
26% ð39Þ
CF3O
F CF3O
CF2CF3
F2, N2, NaF
hν85%
ð40Þ
Perfluorination of hydrocarbons by cobalt trifluoride continues to be used for the manufactureof a range of perfluorinated fluids. In particular, perfluorination of methyl-substituted aromaticsubstrates (Equation (41)) is very useful for the synthesis of trifluoromethylated perfluoroalkanes<1960AFC166>.
CoF3, 360 °C
CF3
F77%
ð41Þ
Trihalides 9
Electrolysis of an organic substrate, dissolved in anhydrous hydrogen fluoride gives the corre-sponding perfluorinated derivatives by electrochemical fluorination (ECF). Starting materials thatare soluble in HF are the most readily fluorinated and many perfluorinated amines (Equation(42)) and ethers have been efficiently synthesized by this methodology <1997TCC(193)197,1988JFC(38)303>.
NHF, electrolysis
N
CF3
F Fð42Þ
6.01.2.3.3 Transfer of trifluoromethyl groups as radicals
Trifluoromethyl radicals may be generated from electrolysis or radiolysis of trifluoroacetic acid orrelated salts or thioesters or by homolytic cleavage of the weak carbon�bromine bond intrifluoromethyl bromide.
Irradiation of trifluoromethylthioacetates or trifluoromethane thiosulfonates gives trifluoro-methyl radicals that react regioselectively with electron-rich alkenes at the least hindered site(Equation (43)). However, some reduction of the thiophenyl group is also obtained, leading to amixture of products <2000TL3069>.
C9H19hν , 40 °CCH2Cl2 CF3
SPh
C9H19CF3 C9H19
+
49% 33%
CF3–SO2–SPh +ð43Þ
Trifluoromethyl radicals, generated by electrolysis of potassium trifluoromethane sulfinate,may be trapped by electron-rich alkenes and aromatic systems (Equation (44)) <2002SL1697>.
C9H19
CF3SO2K, DMF
Et4NClO4
Electrolysis
CF3 CF3 CF3
(69%), ratio 78:12:10
ð44Þ
Radical trifluoromethylation, followed by nucleophilic cyclization in a tandem process(Equation (45)) gives rise to various trifluoromethyl carbohydrate derivatives<1998JFC(91)179>.
O
O
O
HO
S
SCF3Br, HCO2Na
NaHCO3, SO2
O
O
H
HO
O
F3CS
S
72%
ð45Þ
Electrochemical trifluoromethylation of 3-sulfolene (Equation (46)) <1998JFC(87)179> anddimethyl acetylenedicarboxylate <1996JFC(78)193> in a trifluoroacetic acid/aqueous acetonitrilemedium gives mixtures of products. However, radical addition of trifluoromethyl groups, fol-lowed by coupling of the intermediate radical derivatives, provides access to various bis-trifluoro-methylated systems (Equation (47)) <1997T4437>.
SO O
CF3COOH
MeCN, H2OElectrolysis
SO O
CF3 CF3
+S
O O
CF3 CF3
+ Six other products ð46Þ
CN CF3COOH
MeCN, H2OElectrolysis
CF3CF3
CN
CN
25%
ð47Þ
10 Trihalides
6.01.2.3.4 Reactions involving trifluoromethyl derivatives of metals and metalloids
Trifluoromethyltrimethylsilane, CF3TMS, commonly referred to as Ruppert’s reagent<1984TL2195> and now commercially available, was first used for trifluoromethylation ofcarbonyl derivatives (Equation (48)) in 1989 by Prakash and co-workers <1989JA393>:
O
Me3SiCF3
TBAF
CF3 OH
77%
ð48Þ
Efficient trifluoromethylation occurs in the presence of a source of fluoride ion, such ascaesium fluoride, TBAF, TBAT, or amberlite-fluoride resin <2002MI197> whereby fluorideion attacks the silicon atom to release trifluoromethyl anions that are subsequently trapped byan electrophilic carbon site (Scheme 3):
Since the initial reports, the use of TMSCF3 for trifluoromethylation has been reviewedextensively <1997CRV757, 2000T7613, 2001JFC(112)123> and only representative examples ofthe large body of work that has been published are outlined here.
Effective trifluoromethylation of many carbonyl containing systems, such as aldehydes (Equation(49)) <1998JFC(88)79>, ketones (Equation (50)) <1998TA213>, esters, �,�-unsaturated ketones(Equations (51) and (52)) <2000JFC(101)199, 2000OL3173>, �-keto esters (Equation (53))<2000OL3173, 1991SL643>, and lactones (Equation (54)) <1993TL8241> have been described.
Me3SiCF3
TBAF
O
N
O
HBoc
O
N HBoc
CF3OH ð49Þ
O
OO
OO
O
O
OO
OO
HOCF3
Me3SiCF3
TBAF
ð50Þ
OCF3HO
PCC
H2SO4
CF3
O
i. TMSCF3, TBAF (cat.)
ii. TBAF (1 equiv.)
ð51Þ
O
R1 R2
R1 R2
CF3 O Bu4N
Bu4N
+ CF3 SiMe3
SiMe3F
CF3 SiMe 3
R1 R2
CF3 O
SiMe
CF3
MeMe
Bu4N
O
R1 R2
R1 R2
CF3 OSiMe3 HR1 R2
CF3 OH
+
+
–F
–
+
–
+
Scheme 3
Trihalides 11
Ph O
H
Ph OH
CF3
CF3H
O
OHF3C
R3
N
OH
R1 R2
i. TMSCF3, CsF (cat.)
ii. conc. HCl(90%)
i. O3, –78 °C
ii. Me2S
R1R2NHR3-B(OH)2
ð52Þ
OO
O
Me3SiCF3
TBAFO
O
CF3 OH
83%
ð53Þ
Me3SiCF3
TBAF
OO
O
O OO
O
OH
CF3 ð54Þ
In attempts to synthesize enantiopure trifluoromethyl alcohols, chiral triaminosulfonium saltsgave modestly enantioselective catalytic additions to carbonyl systems (Equation (55))<1999TL8231, 2000MI1037>.
PhCHO + TMS-CF3Chiral catalyst
OH
Ph CF3* 52% ee
Chiral catalyst =N
Ph
Ph
S3
Ph3SnF2
96%
ð55Þ
Reaction of Ruppert’s reagent with methyl esters can lead to replacement of the methoxy groupto furnish �-trifluoromethyl ketones (Equation (56)) <1998AG(E)820, 1999JOC2873>:
TMSCF3
TBAFO2N
OMe
O
O2N
CF3
O
81%
ð56Þ
In contrast, nucleophilic substitution of halides by trifluoromethyl anion is very difficult andonly very highly reactive perfluoroalkenes (Equation (57)) <1993IC4802> and acid fluorides(Equation (58)) <1993IC5079> may be functionalized in this manner.
CF3 N
TMS–CF3
KF
CF3
CF3
68%
CF3 N=CF2 ð57Þ
FF
O
F F
F F
O
TMS–CF3
KF CF3CF3
O
F F
F F
O
ð58Þ
Trifluoromethylation of ketones followed by Ritter reaction using acetonitrile in strong acidleads to a variety of trifluoromethylated amides in a one-pot procedure (Equations (59) and (60))<1997SL1193>.
O
PhPh
N
PhPhCF3
HO
TMS–CF3, TBAF (cat.)
CH3CN, H2SO4
68%
ð59Þ
12 Trihalides
O CF3
NH
OTMS–CF3, TBAF (cat.)
CH3CN, H2SO4
54%
ð60Þ
Efficient trifluoromethylation of imines (Equation (61)) <1999TL5475> and other related sys-tems including �,�-unsaturated sulfonaldimines (Equation (62)) <2001SL77>, chiral sulfinimines(Equation (63)) <2001AG(E)589>, and azirines (Equation (64)) <1994TL3303>, in which thecarbon�nitrogen double bond is attacked by trifluoromethyl anion, has been established,giving various trifluoromethylated amine derivatives. In particular, stereoselective addition oftrifluoromethyl groups to imines is possible in systems that possess chiral sulfoxide moietiesadjacent to the carbon�nitrogen double bond <2001AG(E)589>.
N
R2R1
R3
NR3
HR2
CF3R1i. TMSCF3, TMS-imidazole, CsF, THF
ii. SiO2, 2 M HClð61Þ
Cl
N
HSO2tol
Cl
N
CF3
SO2tol
H
TMSCF3
TBAT
87%
ð62Þ
H
NS
t-Bu
O
O NS
t-Bu
O
OH
CF3
TMSCF3
TBATH3N O
CF3
Cl 97:3 diastereomers
HCl, MeOH
85%
ð63Þ
N
PhR2
R1 TMSCF3
TBAF N
PhR2
R1
F3C
SiMe3
ð64Þ
Nucleophilic trifluoromethylation by germanium reagents, which are analogous to thetrimethylsilyl systems described above, also trifluoromethylate C¼N double bonds (Equation (65))<1997TL3443, 1996SL1191>.
PhNPh
HMPAPh
NPh
CF3
H96%
C6H5SCF3
Et3GeNa ð65Þ
Whilst the use of Ruppert’s reagent is becoming widespread, the development of other sourcesof trifluoromethyl anion continues. Successful application of fluoroform (Equation (66))<1998TL2973, 1999T275> and hemiaminals of fluoral, derived from either DMF<2000JOC8848, 2000TL8777> or morpholine (Equation (67)) <2000OL2101>, for analogoustrifluoromethylations of ketones has been discussed by Langlois <2003S185, 2001EJO1467>.
Ph H
O
Ph H
CF3 OH
DMF
HCF3, ButOK ð66Þ
Trihalides 13
ON OTMS
CF3
+R1 R2
OTBAF
R1 R2
CF3 OTMS ð67Þ
Addition of N,N-dimethyltrimethylsilylamine to trifluoroacetophenone gives a stable nucleo-philic trifluoromethylating reagent (Equation (68)) that reacts with carbonyl derivatives uponcatalysis by caesium fluoride <2002SL646>. Related reagents may also be derived from varioustrifluoromethylamides (Equations (69) and (70)) <2003SL230, 2003AG(E)3133> and sulfinates(Equation (71)) <2003SL233>:
Ph CF3
O
+ Me2N–SiMe3110 °C
Ph CF3
Me2N OTMS R1 R2
O
R1 R2
HO CF3
CSF
ð68Þ
CF3 NN
O
Bn
ButOK
DMF, THFPh Ph
O+
Ph Ph
HO CF3
100%
ð69Þ
Ph H
O
+NPh
CF3
OMe3SiO
Ph
i. CsF
ii. Bu4NF Ph CF3
OH
89%
ð70Þ
CF3S
OtBu
O ButOK
THFPh
O
+ Ph
HO CF3
91%N N
ð71Þ
A further nucleophilic trifluoromethylating reagent may be generated by a single-electron transferprocess from the highly electron-rich alkene, tetrakis(dimethylamino)ethylene, to trifluoromethyliodide. A complex between the TDAE dication and trifluoromethyl anion is thought to be the activereagent which may be used to synthesize �-trifluoromethyl alcohols (Equation (72))<2001OL4271>,trifluoromethyl alcohols (Equation (73)) <2002OL4671> and give bis-trifluoromethylation of acidhalides, proceeding via the trifluoromethyl ketone (Equation (74)) <2002TL4317>:
OS
O
OO
+ CF3I +Me2N
Me2N
NMe2
NMe2
TDAE
THF CF3HO55% ð72Þ
+ CF3I + TDAEDMF
Ph H
O
Ph H
HO CF3
78%ð73Þ
+ CF3I + TDAEEt2O
Ph Cl
O
Ph CF398%
CF3
O Ph
O
ð74Þ
A combination of an electron-rich phosphene and trifluoromethyl bromide may add to amideswhich are activated by a Lewis acid. Dehydration results in the formation of trifluoromethylenamines (Equation (75)) <1995JFC(70)89>:
P(NEt2)3, CF3Br
BCl3N CH3
OCH3
CH3
N
CF3
CH3
CH3
H
H25%
ð75Þ
14 Trihalides
Trifluoromethylcopper may be generated from a variety of sources including reaction of eitherCF3I, CF3Br, or trifluoromethanesulfonyl chloride with copper powder in aprotic solvents or fromsodium trifluoroacetate and copper(I) iodide <1995COFGT(6)1>. This trifluoromethylatingreagent generated in situ is effective for the replacement of halogens attached to aromatic ringsystems and also useful for the stereoselective transformation of haloalkenes into trifluoromethylalkenes (Equations (76)–(78)) <1995JFC(72)241, 2001TL5929, 2001JFC(108)79, 2002JOC9421>such as in steroidal alkenyl bromides <1998JCS(P1)1139>.
NO2
Br
CO2EtNO2
CF3
CO2EtFSO2CF2CO2Me
CuI, DMF
91%
24/1 (E )/(Z ) ð76Þ
O OI
CO2EtFSO2CF2CO2Me
CuI, DMFO O
CO2Et
81%
9/1 (Z )/(E )CF3
ð77Þ
FSO2CF2CO2Me
NaF, diglymeIPh
Ph I
F F
82%
FSO2CF2CO2Me
CuI, DMF Ph CF3
F F
45%
ð78Þ
Stereo- and regioselective replacement of terminal iodine atoms in 1,2-diiodoalkenes occursupon treatment with trifluoromethylcopper. An excess of the trifluoromethylation system allowsthe synthesis of ditrifluoromethyl alkenes from di-iodoalkene precursors (Equations (79)–(81))<1998JOC9486>:
Ph
I
I
FSO2CF2CO2Me
CuI, DMF Ph
I
CF390%
ð79Þ
MeO2C
I
I
FSO2CF2CO2Me
CuI, DMF MeO2C
I
CF388%
ð80Þ
Ph
I
I
2.5 equiv. FSO2CF2CO2Me
CuI, DMF Ph
F3C
CF391%
ð81Þ
Similar processes are effective in the presence of a palladium species which catalyzes insertionof trifluoromethyl group into carbon�halogen bonds (Equation (82)) <2001JFC(111)185>:
NO2
Br
Br
FSO2CF2CO2Me
CuI, Pd(PPh3)4 NO2
CF3
CF3
82%
ð82Þ
Trihalides 15
Allyl iodides are displaced by trifluoromethyl upon reaction with chlorodifluoroacetate andfluoride ion in the presence of copper(I) iodide (Equation (83)). The process probably occurs viacarbene type mechanism, although this is not clear <1998TL3961>.
MeSO2 IClCF2CO2Me
KF, CuI, DMFMeSO2 CF3
43%
ð83Þ
6.01.3 TRICHLOROMETHYL DERIVATIVES, R�CCl3
6.01.3.1 Trichloromethyl Groups Attached to an Aliphatic Center
6.01.3.1.1 Conversion of groups attached to an aliphatic center into the trichloromethyl group
The most direct and industrially important method of introducing trichloromethyl groups into analiphatic system remains sequential chlorination, in the presence of a Lewis acid, followed bydehydrochlorination (Equation (84)).
ClCl2
Cl
Cl
Cl–HCl
Cl
Cl HCl
Cl
ClCl ð84Þ
6.01.3.1.2 Transfer of the trichloromethyl group to an aliphatic center
Trichloromethyl anions may be generated from chloroform/BuLi, chloroform/NaOH, orTMSCCl3/base, and react with various organic substrates that possess electrophilic carbon sites.However, trichloromethyl anion is relatively unstable and must be generated at low temperature(��100 �C) before loss of chloride ion, giving reactive dichlorocarbene, occurs as a competingprocess leading to the formation of unwanted side products. Nevertheless, some useful synthesesutilizing trichloromethyl anions have been developed. Michael-type addition processes (Equations(85) and (86)) to a range of electron-poor alkenes occur to give corresponding trichloromethyladducts <1993JOC267, 1999OL2165> and �-trichloromethyl alkanes may be prepared by reac-tion with sufficiently activated haloalkanes (Equation (87)) <1990JOC1281>.
OEt
O
PPh3
OCHCl3, BuLi
THF OEt
O
PPh3
O
Cl3C
90%
ð85Þ
CHCl3, BuLi
NSO O
O
TMSCl NSO O
O CCl3
55:45 ratio of diastereoisomers
75%
ð86Þ
CHCl3, BuLiEt HMPAI Et CCl3
68%
ð87Þ
Chloroform may be deprotonated by aqueous sodium hydroxide in the presence of a quatern-ary ammonium salt to give trichloromethyl anion which exists in equilibrium with dichloro-carbene. In general, for this reagent system, electron-rich alkenes react with dichlorocarbene,whereas electron-poor alkenes react by conjugate addition (Equation (88)). The reaction outcomeis sensitive toward the type of ammonium salt present as the phase-transfer catalyst<1997T1053>. Lipophilic salts are more effective at promoting conjugate addition, rather thancompeting cyclopropanation involving dichlorocarbene addition. Indeed, catalysts may be
16 Trihalides
designed so that only products arising from Michael addition are obtained, providing a poten-tially useful solution to the problem of competing dichlorocarbene reactions <1999T6329,2003PJC709>.
OCOPh
CHCl3, 50% aq. NaOH
PTC OCOPh
CCl3
OCOPh
ClCl
+
PTC = Me4NHSO4 5% 68% BnEt3NCl 65% —
ð88Þ
6.01.3.2 Trichloromethyl Groups Attached to an Aromatic Ring
6.01.3.2.1 Conversion of groups attached to an aromatic ring into a trichloromethyl group
Free-radical chlorination, initiated by either heat or radiation, of methyl groups attached toaromatic and heteroaromatic rings bearing a range of functionalities are well established(Equation (89)), as discussed in COFGT (1995). Alternative methodologies to these industriallyoperated processes have not been generally developed:
Cl2
Heat or hν
CCl3ð89Þ
6.01.3.2.2 Transfer of trichloromethyl group to an aromatic ring
Aromatic systems may be trichloromethylated by reaction with carbon tetrachloride and a Lewisacid, usually aluminum trichloride, by Friedel–Crafts process. Trichloromethyl derivatives are themajor products but further Friedel–Crafts reaction of this system may take place to yield thecorresponding diaryldichloromethane (Equation (90)) <1987JPR1131>. Carbocation rearrange-ments may occur in the highly acidic reaction medium, for example, durene gives exclusivelya product arising from acid catalyzed rearrangement (Equation (91)) <1960JA4460>. Acidcatalyzed oligomerization of 2,4-disubstituted thiophenes occurs upon reaction with the carbontetrachloride/aluminum trichloride reagent system <1998CHE1276>.
CCl4, AlCl3CCl3
+
ClCl
ð90Þ
CCl4, AlCl3CCl3
ð91Þ
6.01.4 TRIBROMOMETHYL DERIVATIVES, R�CBr3Methodologies for the synthesis of tribromomethylated derivatives are analogous to processesuseful for the preparation of corresponding trichloromethyl systems. Tribromomethyl anions,generated from either decarboxylation of tribromoacetic acid <1967JOC2166> or tributyl(tribromomethyl)stannane <1975JOM(102)423>, react with electrophilic carbon centers,although development of this methodology remains very limited.
Trihalides 17
6.01.5 MIXED SYSTEMS WITH FLUORINE, R�CF2Hal AND RCFHal2
Many systems bearing CF2Hal and CFHal2 groups are synthesized as by-products of the varioushalex reactions described above. Other more general syntheses, involving either displacement offluorine or the transfer of such groups onto organic substrates, are noted below.
Transformation of �-trifluoromethyl ketones to corresponding difluorohalo derivatives can beaccomplished in two steps (Equations (92) and (93)) involving halogenation of the trimethylsilylenol derivative of the starting ketone <2003JFC(121)239>.
Cl
CF3
O
Mg, TMS–Cl
THFCl
OSiMe3
F
F
I2
Cl
CF2I
O
60%
ð92Þ
F3C
CF3
O
Mg, TMS–Cl
THFF3C
OSiMe3
F
F
Br2
F3C
CF2Br
O
87%
ð93Þ
Various difluorobromo- and difluorochloromethyl-substituted derivatives may be formedupon condensation of bromodifluoroacetate (Equations (94) and (95)) <1999JFC(95)127> ordifluorochloroacetic anhydride (Equation (96)) <2001SL821> with an appropriate nucleophile.
NH2
OH
+O
BrCF2 OEt
EtOAcEt3N
HN
OH
CF2Br
O
i. PPA, 150 °C
ii. NH3 (aq.)O
NCF2Br
73%
ð94Þ
N
Ph NH2
OH
+O
BrCF2 OEt
Heat
NO
N
CF2Br
Ph
35% ð95Þ
NNMe2
(ClCF2CO)2O
Pyridine
NNMe2
O CF2Cl75%
ð96Þ
Difluorochloromethyl groups may be introduced into organic systems by the use of a siliconreagent that is analogous to Ruppert’s reagent (Equations (97) and (98)). The difluorochloro-methylating reagent is synthesized by reaction of trimethylsilyl chloride with difluorobromochloro-methane in the presence of aluminum <1997JA1572>:
O
Ph H+ Me3SiCF2Cl
THF, NMP
TBAF
OH
Ph CF2Cl
68%
ð97Þ
O
H+ Me3SiCF2Cl
THF, NMP
TBAF
OH
CF2Cl
85%
Ph Ph ð98Þ
6.01.6 MIXED HALOFORMS, CHXY2 AND CHXYZ
Recent interest in simple haloforms has concentrated upon the synthesis and spectroscopicmeasurement of enantiomerically pure samples of simple chiral systems such as CHClFI andCHFClBr. Decarboxylation of appropriate polyhalogenated acetic acids proceeds with retentionof configuration allowing the isolation of pure enantiomers <2000MI429, 2003MI541>.
18 Trihalides
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Trihalides 19
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Trihalides 21
Biographical sketch
Graham Sandford was born in Manchester. He studied at DurhamUniversity, where he obtained a B.Sc. in 1988 and his Ph.D. in 1991under the direction of Professor R. D. Chambers. After spending 1992 inthe laboratories of Professor G. A. Olah at USC, Los Angeles, hereturned to Durham as a BNFL Postdoctoral Research Fellow. Subse-quently, he was awarded a Royal Society University Research Fellow-ship in 1996 and took up his present position as Lecturer in Chemistry atDurham in March 2001. His scientific interests include all aspects oforganofluorine chemistry, in particular, selective fluorination methodo-logy, heterocyclic, free-radical and carbanion chemistry of fluorinatedsystems.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 1–22
22 Trihalides
6.02
Functions Containing Halogens
and Any Other Elements
J. SUWINSKI and K. WALCZAK
Silesian University of Technology, Gliwice, Poland
6.02.1 FUNCTIONS CONTAINING HALOGEN AND A CHALCOGEN 246.02.1.1 Halogen and Oxygen Derivatives (R1CHal2OR2 and R1CHal(OR2)2) 246.02.1.1.1 Tetracoordinated carbon atoms with two identical halogen
and one oxygen function attached (R1CHal2OR2) 246.02.1.1.2 Tetracoordinated carbon atom bearing mixed halogens
and one oxygen function (R1CHal2OR2) 326.02.1.1.3 Tetracoordinated carbon atom bearing one halogen
and two oxygen functions (R1CHal(OR2)2) 336.02.1.2 Halogen and Sulfur Derivatives (R1CHal2SR
2 and R1CHal(SR2)2) 336.02.1.2.1 Tetracoordinated carbon atoms with two identical halogen and one sulfur function attached
(R1CHal2SR2) 34
6.02.1.2.2 Tetracoordinated carbon atoms bearing mixed halogens and one sulfur function(R1CHal2SR
2) 496.02.1.2.3 Tetracoordinated carbon atoms bearing one halogen and two sulfur functions
(R1CHal(SR2)2) 506.02.1.3 Halogen and Se or Te Derivatives (R1CHal2SeR
2 or R1CHal2TeR2) 50
6.02.1.3.1 Tetracoordinated carbon atoms bearing two halogens and one selenium function(R1CHal2SeR
2) 506.02.1.3.2 Tetracoordinated carbon atoms bearing two halogens and one tellurium function
(R1CHal2TeR2) 52
6.02.1.4 Halogen and Mixed Chalcogen Derivatives (R1CHal(OR2)(SR3)) 526.02.2 FUNCTIONS CONTAINING HALOGEN AND A GROUP 15 ELEMENT
AND POSSIBLY A CHALCOGEN 536.02.2.1 Halogen and Nitrogen Derivatives: General Considerations 536.02.2.1.1 Tetracoordinated carbon atoms bearing two halogens and one nitrogen function 536.02.2.1.2 Tetracoordinated carbon atoms bearing one halogen and two nitrogen functions 596.02.2.1.3 Tetracoordinated carbon atoms bearing one halogen, one nitrogen, and one oxygen function 616.02.2.1.4 Tetracoordinated carbon atoms bearing one halogen, one nitrogen,
and one sulfur function 626.02.2.2 Halogen and Phosphorus Derivatives 626.02.2.2.1 Tetracoordinated carbon atoms bearing two halogens and one phosphorus function, and one
halogen and two phosphorus functions 626.02.2.2.2 Tetracoordinated carbon atoms bearing one halogen, one oxygen function,
and one phosphorus function 636.02.2.3 Halogen and Arsenic Derivatives 636.02.2.3.1 Tetracoordinated carbon atoms bearing two halogens and one arsenic function 63
6.02.3 FUNCTIONS CONTAINING HALOGEN AND A METALLOIDAND POSSIBLY A CHALCOGEN AND/OR GROUP 15 ELEMENT 64
6.02.3.1 Halogen and Silicon Derivatives 646.02.3.1.1 Dichlorocarbene addition 646.02.3.1.2 Other additions to silanes 646.02.3.1.3 Substitution of silanes by haloalkyl derivatives 64
6.02.4 Halogen and Boron Derivatives 656.02.5 Halogen and Germanium Derivatives 65
23
6.02.6 FUNCTIONS CONTAINING HALOGEN AND A METAL AND POSSIBLY A GROUP 15ELEMENT, A CHALCOGEN OR A METALLOID 65
6.02.6.1 Halogen and Lithium Derivatives 656.02.6.2 Halogen and Magnesium Derivatives 656.02.6.3 Halogen and Copper Derivatives 666.02.6.4 Halogen and Silver Derivatives 666.02.6.5 Halogen and Zinc Derivatives 666.02.6.6 Halogen and Cadmium Derivatives 666.02.6.7 Halogen and Mercury Derivatives 676.02.6.8 Halogen and Tin Derivatives 676.02.6.9 Halogen and Lead Derivatives 686.02.6.10 Halogen and Ruthenium Derivatives 686.02.6.11 Halogen and Cobalt or Nickel Derivatives 686.02.6.12 Halogen and Palladium or Platinum Derivatives 69
6.02.1 FUNCTIONS CONTAINING HALOGEN AND A CHALCOGEN
Apart from broad overviews of haloalkyl systems relevant to this chapter and covering theliterature up to 1984 <1985HOU(E5)> and up to 1994 <1995COFGT(6)35> no report of thistype has ever been published.
A few limited reviews which concentrated mainly on fluorinated oligo- and polymeric materialscontaining -(CF2O)n- or -(CF2S)n fragments were published. A review seeking to cover recentdevelopments in the field of fluorinated elastomers was published in 2001 <2001MI105>.Heteroatom-containing fluoroelastomers were briefly summarized there (pp. 144–147). The fol-lowing structures were discussed: -(CF2O)n-, -(CF2S)n-, -(N-OCF2CF2)n-. Also nitrile-containingfluoroelastomers (NC-(CF2)n-O-CF�) were presented. A review on polymers (containing OCF2
fragments), which can be applied to a variety of surfaces and manufactured into thin films, hasbeen recently published by Imae <2003MI(8)307>. Caminade et al. published a review onfluorinated dendrimers (some containing OCF2 fragments) and their applications in catalysis,material sciences, and biology <2003MI(8)282>. Application of several different perfluoroalkylcompounds, e.g., perfluoroethers in the biomedical field; in in vivo transport of O2, CO2, and NOwas reviewed earlier <1998MI(80)489>.
6.02.1.1 Halogen and Oxygen Derivatives (R1CHal2OR2 and R1CHal(OR2)2)
6.02.1.1.1 Tetracoordinated carbon atoms with two identical halogenand one oxygen function attached (R1CHal2OR2)
(i) From ethers
Direct halogenation of ethers remains the simplest method for synthesis of perhalogenatedcompounds of this class. Fluorination of low-molecular weight ethers using elemental fluorinegives products with ratio being a function of the flow rate of fluorine and of carrier gas (usuallyhelium). Direct fluorination of dioxane using elemental fluorine has afforded perfluorinatedsystem in a moderate yield, whereas application of a mixture of sulfur tetrafluoride and hydrogenfluoride has led to the formation of 2,2,3-trifluorodioxane in a high yield. Electrochemicalfluorination of ethers leads to perfluorinated products in moderate yields. Electrochemical fluor-ination of a range of oxanes also results in the formation of the corresponding perfluorinatedproducts in only moderate yields <1995COFGT(6)35>.
Combination of sodium fluoride and elemental fluorine has successfully been applied tofluorination of ethers in perhalogenated alkanes as the solvents. The appropriate perfluorinatedethers were obtained in high yields (Scheme 1) <1995JA4276, 1996SC375>. Fluorination of5,7,9,11-tetraoxapentadecane using the same system has produced a mixture of perfluorinatedethers resulting from chain cleavage <1995JA4276, 1996SC375>.
Fluorination of an alkoxyalkyl ester of perfluorinated acid using elemental fluorine at elevatedpressure affords perfluorinated product in a moderate yield. It is worth mentioning that the esterfunction is preserved (Equation (1)) <2001JFC(112)109>.
24 Functions Containing Halogens and Any Other Elements
OO R
OO
O R
O
F F F CF3
F FF
–CF(CF3)OCF2CF2CF3
F
R =
F2, C6H6, 20–40 °C, <1500 torr
75% ð1Þ
Electrochemical fluorination of N-(2-hydroxyethyl)morpholine leads to the corresponding acylfluoride (Equation (2)) accompanied by a mixture of perfluorinated products resulting from thechain or ring cleavage and subsequent fluorination of the produced fragments<1999JFC(97)229>. Tetrahydrofuran, when treated with boron trichloride in the presence ofbis(trifluoromethyl)cadmium-acetonitrile complex, undergoes ring-opening reaction followed byhalogenation to produce 4-chlorobutyl difluoromethyl ether <1995JFC(73)229>.
O
N
OH
O
N
F
OFF
F
25%
HF, 7–8 °C, ~10 h ð2Þ
Photochlorination of partially fluorinated ethers was also investigated; the appropriate chloro-ethers have been obtained in moderate yields <1995JOC1319>. Chlorination of p-methoxybenzoylchloride using chlorine in the presence of phosphorus pentachloride affords p-(trichloromethoxy)-benzoyl chloride in an excellent yield (Equation (3)) <2000JFC(103)81>.
MeOO
ClCl3CO
O
Cl92%
PCl5, Cl2, 200 °C ð3Þ
(ii) From mixed trihalomethanes
No further advances have occurred in this area since the publication of <1995COFGT(6)35>.
(iii) From dihaloethers
Selective further fluorinations of haloethers using manganese trifluoride or sodium fluoride havebeen reported (Scheme 2) <1996JFC(80)86, 1997JFC(85)111>.
Treatment of haloethers, containing a mixed halogen function, with sevoflurane (1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane) in the presence of antimony pentachloride <1998JFC(88)51,2001JFC(111)11> or bromine trifluoride <2000JFC(102)363> results in halogen substitution. Inthe latter reaction respective fluorinated ethers have been obtained in moderate to good yields(Scheme 3). Substitution of a chlorine atom in trichloromethyl group using sevoflurane and antimonypentachloride was reported later <1999JFC(94)1>. A fluorine atom through a reaction with hydro-gen fluoride in the presence of cobalt difluoride and porous aluminum trifluoride can substitute an�-chlorine atom in mixed haloalkoxyalkanes (Scheme 3) <2001JFC(112)145>.
O O F3C O O CF3
F F
F F
F F F F F
F F
F FF
O
OF3C O O CF3
F
F F
F F F F F
F F
F FF F
75%
32%33
F2, NaF, ClF2CCCl2F
F2, NaF, ClF2CCCl2F
Scheme 1
Functions Containing Halogens and Any Other Elements 25
Polyfluorinated ethers RfCH2ORf react with fluoroethylenes in the presence of SbF5 catalystunder mild conditions. The reaction of CF3CH2OCF2CF2H with F2C¼CF2 results in theformation of CF3CH2OCF(C2F5)CF2H in a high yield. In contrast to that, the condensation ofCF3CH2OCF2CF2H with F2C¼CFH affords CF3CH2OC(CHFCF3)CF2H as a major product(Scheme 4). A mechanism for the reactions was discussed <2001JFC(112)117>.
A chlorine atom in polyfluorinated ether was exchanged by a fluorine one using trifluoroboride(Equation (4)) <1993JPS791>.
BF3 F2HCF
O CF3HF2HC
Cl
O CF3H ð4Þ
Transformations of polyfluoroalkyl ethers have also been described <2002JFC(114)51>. Lubri-cating oils and greases for magnetic recording devices, containing partially esterified phosphatesand phosphonates or salts of phosphate and phosphonate esters were prepared by reaction ofmixed perfluoroalcohols or perfluorodiols with a phosphorus acid precursor i.e., phosphorusoxychloride in the presence of an amine acid scavenger <2003USP073588>.
O
F
F
Cl
F Cl
OCl3C
CF3
CF3
O F3
CF3F
ClCl
O
F
F
Cl
F F
O
CF3F
Cl CF3O
CF3F
F F3
66%
90%
SbCl5, sevoflurane
5SbCl , sevoflurane, 5–10 °C, 1 h
CoF2, HF, AlF3, 200 °C, 1 h
85%
C
C
Scheme 3
F3C OF
F F
FH F3C O
FF CF2CF3
FH
F3C OF
F F
FH
F3C OF
F3CHFC CHFCF3
FH
F2C=CF2, SbF5, 25 °C, 12 h
76%
F2C=CHF, 25 °C, 5 h
61%
Scheme 4
O
F
CF3F OF3C
CF3
F F
O CClF2F3C O
F
FF F
OF
ClF F
OF
Cl CH2FF F
45%
65%
85%
MnF3, 75 °C, 6 h
NaF, 85–95 °C, 6 h
MnF3, 50 °C, 5 h
Scheme 2
26 Functions Containing Halogens and Any Other Elements
(iv) From carbonyl derivatives
Several methods for conversion of carbonyl compounds into ethers perhalogenated in alkyl(cycloalkyl) groups have been described. Among others electrochemical fluorination of acylchlorides and esters has been used. The sulfur tetrafluoride has been applied for conversion ofa variety of anhydrides, esters, and formate esters into compounds with difluoromethyl groups.Aromatic o-diacids treated with sulfur tetrafluoride can form cyclic ethers in addition to per-fluorination of other substituents <1995COFGT(6)35>.
Phosphorous pentachloride, which reacts with a variety of formate esters to yield the correspond-ing �,�-dichloro diethers <1995COFGT(6)35>, has recently been used successfully for the conver-sion (Scheme 5) of methyl formate <1996ZOR1186> and diphenyl carbonate <1996AJC1261>.
Acyl fluorides can be transformed in moderate yields into perfluoroalkyl methyl ethers usingtriethylamine–hydrogen fluoride complex (Equation (5)) <2002JFC(118)123>. Oxalyl difluoridetreated with ethyl ester of trifluoromethanesulfonic acid has afforded ethoxy-difluoroacetylfluoride in a moderate yield (Scheme 6) <2002JFC(113)97>. Oxalyl difluoride has also beenused in reaction leading to the ring-opening in perfluorinated (methyl)oxiranes (Scheme 6)<1995JFC(75)163>. Perfluorinated (methyl)oxiranes when treated with several fluorinatingagents gave appropriate derivatives of perfluorinated alkoxy acetyl fluorides in moderate-to-goodyields (Scheme 7) <1996T9755, 2002JFC(114)51, 1999ZPK(72)425>. The use of ammonium- andphosphonium perfluorocyclobutane ylides, prepared with perfluorocyclobutene and tertiary aminesor phosphines as a masked fluorine anion source, has been demonstrated in severalreactions <1996T9755>.
F3C
F F
F
Et3N.3HF, EtOH
(CH3O)2SO2F3C
OF F
FO
F68%
ð5Þ
The reactions of oxalyl fluoride with electrophiles in the presence of alkali metal fluorideafford �,�-difluoroethers. In the reaction with CF3CH2O3SCF3 or CH3CH2O3SCF3, synthesisof di-ether (ROCF2CF2OR) and mono-ether as a by-product (ROCF2COF) was achieved(Scheme 8) <2002JFC(113)97>.
H
O
OMePCl5
MeO Cl
PhO OPh
O
PhO OPh
Cl Cl
97%
PCl5, 180 °C, 24 h
Cl
Scheme 5
OF
OF F
OS
F3C
O
O
F
O
O
F
O
F
F3C
F
FF
OO
F
O
F F F F
F F F CF3O
F
O
F
O
58%
71%
CsF, diglyme, 20 °C, 24 h
KF, 0 °C, 16 h
Scheme 6
Functions Containing Halogens and Any Other Elements 27
A new synthetic procedure for the preparation of perfluoro(alkoxyalkanoyl) fluorides, precursorsof perfluorinated vinyl ether monomers, from nonfluorinated alkoxyalcohols has been developed.The desired perfluoro(alkoxyalkanoyl) fluoride can be obtained from its hydrocarbon counterpartalcohol and an available perfluoroacyl fluoride as is shown (Scheme 9) <2001JFC(112)109>.Transformation of benzaldehydes to difluoromethoxybenzenes using xenon difluoride is enhancedby silicon tetrafluoride <1999JFC(98)163>. It was also found that a relatively new reagent namelybromine trifluoride converts aliphatic nitriles into trifluoromethyl group when a neighboringcarboxylic moiety is present. In the case of ketonitrile, a participation of the internal nucleophilicoxygen in attacking the nitrile carbon was also observed <2001JFC(111)161–165>.
(v) From alkoxyhaloalkenes
Addition of fluorine to the double bond in alkoxyfluoroalkenes has not been reported in reviews yet.It can be achieved using some fluorinating agents like hydrogen fluoride, boron trifluoride, or cobalttrifluoride to afford products, in which former alkene substituents are perfluorated while alkoxygroups do not contain additional fluorine atoms. Yields of the products depend both on thefluorinating agent and reaction conditions (Scheme 10) <1996JOC9605, 2000MI(3)343>.Preparation of alkoxydi(tri or tetra)chloroalkanes by addition of dry hydrogen chloride or drychlorine to alkoxychloroalkenes has already been discussed <1995COFGT(6)35>. More recentreports on chlorination or bromination of alkoxyhaloalkenes have not been located.
(vi) From haloalkenes
The addition of primary alcohols to halogenated alkenes proceeds rapidly in the presence of metalalkoxides, giving the corresponding alkoxyhaloalkanes in high yields <1995JFC(74)273,1997AG136, 2000JFC(102)363>. Also a variety of primary and tertiary alkyl hypohalidesare added at low temperatures affording respective addition products in high yields<1995JFC(74)199>.
O
F
F3C
F
F F3CO
F
FF
F F F CF3
O
O
F
F3C
F
FF3C
OO
F
F F F CF3F F
F F F CF3
O
22%
82%
.
CsF, various solv.
Et3NC4F7 BF4, MeCN, 2 h
Scheme 7
OF
OFF3C O
O CF3F F
F FDiglyme 56%
Tetraglyme 63%
CF3CF2OTf, CsF, rt, 24 h
Scheme 8
F3CO
OC3F7
F OC3F7
F F O
F CF3 RHOHRHO C3F7
OO
F CF3
F C3F7O
O
F CF3
RHO C3F7O
O
F CF3
RFO C3F7O
O
F CF3
99%
NaF (30 mol.%), 140 °C
20% F2/N2, 0.2 MPa
1,1,2-Trichlorotrifluoroethane
25–40 °C, 21–86%
Scheme 9
28 Functions Containing Halogens and Any Other Elements
Perfluorinated vinyl ethers react smoothly with alcohols in the presence of deprotonatingagents to give appropriate ethers in moderate yields (Scheme 11) <2000JFC(106)13,2002JFC(117)149>. Addition of trifluoroethanol to the perfluorinated methyl vinyl ether hasbeen accomplished using aqueous potassium hydroxide at an elevated temperature (Equation (6))<1999JFC(95)5>. Also other compounds containing sufficiently acidic proton can be added toperfluoroalkenes in aprotic solvents in the presence of metal hydroxides (Scheme 12)<1998JCR(S)(4)192, 1998JMC1092, 2000JFC(101)91, 2000JFC(103)129, 2002JFC(117)149>.Addition of alcohols to perfluorinated alkoxyalkenes is also possible under photochemicalconditions <1996JFC(80)135>.
F
F
F
OCF3
F3C OH
F3C O
F F
F
OCF3
92%
KOH, H2O, 100 °C, 20 h ð6Þ
F3CO
O
F F
F F F CF3
F F
F
FF
F3CO
OF F F CF3
F FO
F F
F F F
F3CO O
F
F F
F F F CF3
F
F
F3CO O
OC6H13
F F
F F F CF3F
F F
38%
MeOH, MeONa, 20 °C
54%
n-C6H13OH, BuLi, THF, 20 °C
Scheme 11
N
O
O
OH
FF
CF3FDMF, NaOH,
80%N
O
O
OCF3
F
F F
HOMe
MeOH
FF
F CF3
KOH, DMSO, 60 °C, 5 h
92%O
Me
Me
OF
CF3
F F F
CF3
F F
Scheme 12
F
F
OCF3
F
F
F3C
O
F
F
F
O
F
F3CO
F F
F F FI
F
F3C O
F F
F3CO
F F
F F
45%
84%
ICl, HF, BF3, 70 °C, 20 h
CoF3, –196 to –20 °C, 0.5 h
CoF3, –196 to –20 °C, 0.5 h
55%
Scheme 10
Functions Containing Halogens and Any Other Elements 29
Epoxidation of chloroalkenes is a convenient route to �,�-dichlorooxiranes—useful intermedi-ates in the enantioselective synthesis of azido- and aminoacids. Perfluoroalkenes react with sulfurtrioxide to give cyclic perfluoro-2-�-sulfones in excellent yields. Perfluoroalkenes also reactwith halogen monofluorosulfates to yield both 2-haloalkylfluoroalkyl fluorosulfates and vicinalbis(halosulfonyloxy)fluoroalkanes <1995COFGT(6)35>.
A series of nucleophiles was treated with [1,1,2,4,4,5,7,7,8,8,9,9,9-tridecafluoromethyl-3,6-dioxanon-1-ene] as a representative of perfluoro(alkyl vinyl ethers). All the reactions werecompletely regioselective with the nucleophilic attack on the terminal carbon atom. Reactions ofhydroxy compounds, thiols, and sec-amines afford the desired products, while butyllithium,tributylphosphane, or complex hydrides cause displacement of vinylic fluorine (Scheme 13)<2002JFC(117)149>.
(vii) From thiocarbonyl derivatives
A novel, versatile route to difluoroalkoxyalkanes has been offered using bis(dimethoxyethylene)aminosulfur trifluoride in the presence of antimony trichloride. A number of thiocarbonyl methyl estershave been converted to the corresponding difluoroalkoxyalkanes in high yields (Equation (7))<1999JOC7048, 2000JOC4830>.
R OMe
S
R OMe
FF
R = Ph, 96%; cyclohexyl, 95%
DAST, SbCl3, CH2Cl2, 20 °C, 4 h
ð7Þ
S-Methyl thioxanthates, reacting with hydrogen fluoride or bromotrifluoride in the presence ofDBH (1,3-dibromo-5,5-dimethyl)hydantoin), produce appropriate difluoroalkoxyalkanes. Thelatter reaction can be described as an oxidative desulfurization–oxidation process (Equation (8))<1999JFC(97)75, 2000BCJ(73)471>. Sulfuryl chloride has been used for transformation of acetylmethoxy(thiocarbonyl)sulfide to the corresponding disulfenyl chloride <1997JMC864>.
RO S
S
Me R SMe
F F
R = Decyln, 89%; p -BrC6H4, 62%
70% HF/pyridine, DBH, CH2Cl2, –78 to 0 °C, 1 h ð8Þ
(viii) From mixed haloalkanes
A halogen atom (Cl, Br, or I) at � or � position to a carbon atom bearing fluorine is easily substitutedby the phenolate anion. In the presence of sodium hydroxide the reaction occurs easily in both proticand aprotic solvents. Substitution predominates over elimination and appropriate products areformed in moderate to good yields (Scheme 14) <1997KGS(33)967, 1998T4849, 1999KFZ(33)40,2000JFC(102)369, 2000JFC(105)129, 2001JFC(107)89, 2001JMC2869, 2002T4077, 2002TL7353>.Sometimes pressure is necessary to accomplish the reaction, however, it does not help to preventthe elimination <2001JFC(107)89>.
CF3NuH, BuLi, THF
–75 °C to rt, 5 daysNuF2CCHFOCF2CFO-CF2CF2CF3
CF3
F2C=CFOCF2CFO-CF2CF2CF3
NuH Yield (%)
n-C6H13OH 38 (unstable)n-C16H31OH 41p-F3CSC6H4OH 30PhSH 55Et2NH 52 (unstable)(CH2)5NH 79 (unstable)
Scheme 13
30 Functions Containing Halogens and Any Other Elements
(ix) From trihaloalkyl derivatives
Treatment of 2,2,2-trifluoroethyl chloride with alcohols or phenols and aqueous potassiumhydroxide in an autoclave at 240–280 �C gives the corresponding 2-chloro-1,1-difluoroethyl ethersin good yields (Scheme 15) <2002JFC(113)79>.
(x) From other compounds
Alcohols can be transformed into alkyl perfluoroethyl ethers using 2-trifluoromethyl-1,2-dithia-nylium triflate (Scheme 16) <2003TL5995>.
i. phenol, NaH, DMF, 20 °C, 4 h, 80%
i
72%
Phenol, KOH, H2O, 250 °C, 11 h
36–480 torr
50%
KF, DMSO, 120–130 °C, 6 h
100%
p -cresol, NaH, 1,4-dioxane, ∆, 3 h
26%
p-cresol, KOH, DMSO, 80 °C, 6 h
I
F F
F
F
I
F F
F
F
Cl
F OH
F
OO
O
OHF F
Me
O
F
FF F
Me
O
F
FF F
OEt
O
F3C Cl
HOO
OEt
OO
F F
F
F I
OEt
IO
F
O
OEt
FO
Scheme 14
F3C ClROH, KOH, H2O
60–100 atm. 10–15 h, 250–285 °C ROCl
F F
F3C ClArOH, KOH, H2O
ArOCl
F F
40–50 atm. 250 °C, 11 h
R (%)
Me 55Et 67Bun 42But 0MeCF2 70
Ar (%)
Ph 76p-MeC6H4 73o-MeC6H4 52p-(But)C6H4 67
Scheme 15
Functions Containing Halogens and Any Other Elements 31
Fluorination of esters by gaseous fluorine leads to perfluorination of both alkyl groups withoutaffecting the ester function (Equation (9)) <1998JA7117>. The same concerns fluorination ofalkoxyesters (Scheme 17) <2001JFC(112)109>.
C11H23
O
OC4H9-t
C11F23
O
OC4F9-t
FF
F2, 25 °Cð9Þ
6.02.1.1.2 Tetracoordinated carbon atom bearing mixed halogensand one oxygen function (R1CHal2OR2)
Addition of chlorine to methyl perfluorovinyl ethers has been reported as a versatile route tochlorofluoroethers (Equation (10)) <1996JOC8024, 2001T4111, 1998JFC(88)51>. A highly selec-tive exchange of chlorine by fluorine atom in trichloromethyl group of hexafluoroisopropyltrichloromethyl ether, using dichloroacetyl fluoride, has been observed. The use of antimonypentachloride in a similar process has also been reported <1999JFC(94)1>. Introducing fourchlorine atoms into tetrafluoroethyl methyl ether has been achieved by photochemical chlorinationusing gaseous chlorine (Equation (11)) <1995JOC1319, 1999JFC(93)93>.
F
F
OMe
FOMe
F
FCl
FCl
97%
Cl2, –196 to 20 °C, 5 min ð10Þ
ROH
i. NaH, ii . S
S
CF3 F3CSO3
S S
RO CF3 DBH, HF–PyRO
F
F
F
F
F
R = c-C6H11– 83%; p-O2NC6H4O- 23%54%;
–+
Scheme 16
ClO
O
CF3Cl
O
F
OC3F7
F F
F
F F
F F F CF3
F FCl
OO
CF3Cl
OF
OC3F7
63%
i. F2, 20–40 °C, 0–1500 torr
C10H21O
OCF3
F
O
OC3F769%
F2, 20–40 °C, 0–1500 torrC10F21
OO
CF3
FO
OC3F7
F F
F CF3
OO
O
OF
CF3
O C3F7
78% OO
F3C CF3
O
OF
CF3
O C3F7
FF
FF F
F2, 20–40 °C, 0–1500 torr
i
Scheme 17
32 Functions Containing Halogens and Any Other Elements
F3C OMe
F
F3C OCCl3
F Cl
74%
Cl2, hν, 30 h ð11Þ
Asynthesis of chiral enantiomerically pure chlorofluoromethyl tetrafluoroethyl etherswas described.The starting racemic trichloromethyl ether was subjected to fluorination with antimony trifluoride–bromine giving dichlorofluoromethyl ether in 51% yield. Irradiation of the latter with UV light in2-propanol afforded racemic ether in 49% yield. Application of the above conditions to enantiomeri-cally pure (R) and (S) ethers gave the target ethers respectively with only a very little erosion of theenantiomeric excess (ee). The importance of the latter result comes from the following: volatilehalogenated chiral ethers are often used as anesthetics; in common with many other chiral pharma-ceuticals, the optical antipodes can differ in pharmacological profile (Scheme 18) <1995JOC1319>.
6.02.1.1.3 Tetracoordinated carbon atom bearing one halogenand two oxygen functions (R1CHal(OR2)2)
Compounds with a tetracoordinated carbon atom bearing one halogen and two oxygen atomsseem to be quite common and well known. Numerous examples of compounds of this class existand their syntheses have been reviewed <1995COFGT(6)35>. The compounds are usually pre-pared either from 1,3-dioxolanes or from o-formates using a variety of halogenating agents.
More recently one unusual example of the synthesis has been reported. Fluorosulfonic acid andsulfur dichloride reacting with trifluoromethyl trifluorovinyl ether yielded a product containingrests of both reagents added to the starting alkene. The products contain a tetracoordinatedcarbon atom bearing one halogen and two oxygen atoms (Scheme 19) <1996IZV(7)1745>.
It appears that no further advances have occurred in this area since the publication of<1995COFGT(6)35>.
6.02.1.2 Halogen and Sulfur Derivatives (R1CHal2SR2 and R1CHal(SR2)2)
The synthetic methods for preparing carbohydrates bearing a C-branched substituent of the typeCF2-Y (e.g., n-CnF2n+1) where Y=heteroatom (O, S, P) were reviewed by Plantier and Portella.Examples of the syntheses are given in Scheme 20 <2000CAR119>.
Cl3CO CF3
F H 45–56%
SbF3, Br2O CF3
F H
F
ClCl
2-Propanol, hν
43–47%
O F3
F H
F
ClH
C
Scheme 18
F
F
F
O CF3
SCl2, HSO3F, 30–35 °C
33%F
SO
F O CF3
SF F
Cl
O O
Scheme 19
O
F
F
(OR)3
O
F
FSPh
(OR)3
OF
F
(OR)4
OF
FSPh
(OR)4
PhH, ∆, 79%
PhSH, AIBN
PhH, ∆, 92%
PhSH, AIBN
Scheme 20
Functions Containing Halogens and Any Other Elements 33
6.02.1.2.1 Tetracoordinated carbon atoms with two identical halogenand one sulfur function attached (R1CHal2SR
2)
(i) From sulfides
Halogenation of sulfides is the most popular method for the preparation of compounds describedin this sub-chapter. Several new examples of fluorination of sulfides, containing other functionalgroups (not reported in <1995COFGT(6)35>) concern reactions under electrochemical conditions.The first reports on electrochemical difluorination of sulfides published by Fuchigami andco-workers appeared in 1995 (Scheme 21) <1995JOC3459, 1995JFC(73)121>.
Carbonyl group or triple C�C bond can serve in those fluorinations as activating groups(Scheme 22) <2001TL3009, 2002T5877>.
Triethylamine–hydrogen fluoride complex was also used under electrochemical conditions forfluorination of sulfides in the �-position to sulfur atom in compounds containing carboxyamidegroup (Equation (12)) <1999JFC(93)53>.
Ph SNH2
OPh S
NH2
O
F FElectrolysis, 27% (not isolated)
Et3N–3HF, MeCNð12Þ
�,�-Difluorination of unactivated methylene group in sulfide was reported too (Scheme 23)<2001TL4861>.
PhS
OEt
F
O
PhS
OF
O
F
Electrolysis, 57%
i. Et3N–3HF, MeCNii. aq. NH4OH
Et
Scheme 21
PhS
O
O
PhS
O
O
F F
Ph S Ph S
F FElectrolysis, 77%
MeOOMe
Et3N–5HF,
Electrolysis, 11%
Et3N–3HF, MeCN
Scheme 22
PhS
O
O
OPh
S
F FO
O
O
Electrolysis, 40 °C, 68%
MeOOMe
Et3N–3HF,
Scheme 23
34 Functions Containing Halogens and Any Other Elements
Sulfides already containing one �-fluoro atom can be fluorinated further to difluoro derivatives(Equation (13)) <1995T2605>.
Ph SPh
F
F
Ph S
F FPhMeCN, 2 h
electrolysis
Et3N–3HF F
ð13Þ
Fluorine atoms exchange with hydrogen in methylene group of sulfides, activated by carbonylor cyano group linked to sulfur, in reactions with tetraethylammonium fluoride–hydrogen fluor-ide complex (Scheme 24) <1997JOC8579>.
Electrochemical conditions have also been applied to difluorination of quinolin-2-yl propan-2-on-1-yl sulfide (Equation (14)) <1999JOC138>.
N S
O
N S
O
FF
MeOOMe
Electrolysis, 5%(not isolated)
Et4NF–3HF,
ð14Þ
When the reaction of fluorination of sulfides is carried out in the presence of 1,3-dibromo-5,5-dimethylhydantoin, fluorine atoms can substitute both hydrogen atom and carboxylic groupattached to a methylene carbon atom (Scheme 25) <1998JFC(87)215>.
Addition of pentafluoroiodine to triethylamine–hydrogen fluoride complex enables one toperform difluorination in hydrocarbon solvents without electrolysis. Usually improved(moderate or high) yields of products are obtained, though the reactions carried out atlower temperatures require a considerable length of time (Scheme 26) <2001CL222,2002BCJ(75)1597>.
n-C7H15S CO2Et n-C7H15S CO2Et
F F
Ph SN Ph S
N
F FMeCN, 50%electrolysis
Et4NF–4HF
MeCN, 50%electrolysis
Et4NF–4HF
Scheme 24
Ph SCO2H
C6H4-Cl-pPh S
F
C6H4-Cl-p
F30%
i. Et3N–3HF, CH2Cl2, 1,3-dibromo-5,5-dimethylhydantoin, electrolysis
i
Scheme 25
Functions Containing Halogens and Any Other Elements 35
Rather recently a new fluorinating agent namely N-fluoro-2,4,6-trimethylpyridinium triflate hasbeen shown to efficiently difluorinate several sulfides in the presence of zinc dibromide. Thereaction occurs in chlorinated hydrocarbons at elevated temperatures affording products in highyields (Scheme 27) <2000CPB1097>. In another paper the same authors have reported evenhigher yields of the products (Scheme 28) <2001CPB173>.
PhS
Ph
O
PhS
PhF
O
F
EtS
O
F F
EtS
O
F FF F
PhS
OEt
O
PhS
OF
O
F
Et
PhS
Ph
O
PhS
PhF
O
F
p-ClC6H4 SN
C4H9
O
p-ClC6H4 SN
C4H9
O
F F
PhS
OEt
O
PhS
OF
O
F
Et
PhS
OEt
F
O
PhS
OF
O
F
Et
EtS
O
F F
EtS
O
F FF F
80%
IF5–Et3N–3HF, hexane, 40 °C, 4 h
IF5–Et3N–3HF, hexane, 40 °C, 216 h
36%
IF5–Et3N–3HF, hexane, 40 °C, 216 h
36%
69%
IF5–Et3N–3HF, heptane, 80 °C,12 h
79%
IF5–Et3N–3HF, heptane, 40 °C, 6 h
IF5–Et3N–3HF, hexane, 63 °C, 4 h
59%
IF5–Et3N–3HF, heptane, 74 °C, 1 h
82%
45%
IF5–Et3N–3HF, hexane, 63 °C, 4 h
Scheme 26
p-MeOC6H4 S p-MeOC6H4 S
F F
PhS
Ph
O
PhS
PhF
O
F
i. ZnBr2, N-fluoro-2,4,6-trimethylpyridinium triflate, Cl2HCCH2Cl, 100 °C, 1.5 h
76%
64%
O O
i
i
i. ZnBr2, N-fluoro-2,4,6-trimethylpyridinium triflate, Cl2HCCH2Cl, 105 °C, 1.5 h
Scheme 27
36 Functions Containing Halogens and Any Other Elements
A high yield of difluorinated sulfide can be obtained by the treatment of ethyl �-(phenylthio)-acetate with difluoroiodotoluene in dichloromethane at a low temperature (Scheme 29)<2000TL4463>.
Triethylamine–hydrogen fluoride in acetonitrile, in the presence of zinc dibromide, was used fordifluorination of only one methylene group in 2,8-dioxa-5-thia-nonan-3,6-dione (Equation (15))<2002SL996>.
OS
O
OO
OS
O
OO
F FEt3N–3HF, ZnBr2, MeCN ð15Þ
Moderate yields of �-bromo-�,�-difluoro-�-methylthioketones are obtained from�,�-dimethylthio-�,�-unsaturated ketones by treating them with hydrogen fluoride–pyridine inthe presence of 1,3-dibromo-5,5-dimethylhydantoin (Scheme 30) <1998TL9651> or mercurytrifluoroacetate (Equation (16)) <2000JFC(101)35> as catalysts.
Ph S
F
Et
O F
S
SO
PhPyridine–6HF, Hg(OCOCF3)2, CH2Cl2, 20 °C, 24 h
76%ð16Þ
EtS
O
F F
EtS
O
FF F
PhS
Ph
O
PhS
PhF
O
F
F
i. ZnBr2, N-fluoro-2,4,6-trimethylpyridinium triflate, Cl2HCCH2Cl, 85–105 °C
i
82%
i. ZnBr2, N-fluoro-2,4,6-trimethylpyridinium triflate, Cl2HCCH2Cl
85%
i
Scheme 28
PhS
OEt
O
PhS
OF
O
F
EtDifluoroiodotoluene, CH2Cl2, 0 °C
80%
Scheme 29
Pr S
S
Et
O
Pr S
F
Et
O F
Br
S
SOS
FO F
BrHF, pyridine, i, CH2Cl2, –78 °C, 2 h
39%
HF, pyridine, i, CH2Cl2, –78 °C, 2 h
i = 1,3-dibromo-5,5-dimethylhydantoin
39%
Scheme 30
Functions Containing Halogens and Any Other Elements 37
Dichlorination of sulfides is a popular route to �,�-dichloroalkyl sulfides and can be achievedeasily using several chlorinating agents, e.g., sulfuryl dichloride. Pommelet and co-workerspublished several examples of such chlorination (Scheme 31) <1997T12565, 2002SL996,1996TL2413>.
Partly fluorinated sulfides are dichlorinated in high yields using sulfuryl dichloride in chlori-nated hydrocarbons (Scheme 32) <1997BSF697>. Under the conditions sulfuryl dichloride leavesthe triple C�C bond untouched (Equation (17)) <1997SC2993>.
Ph SC6H13-n
Ph SC6H13-n
ClCl
SO2Cl2, CCl4, 0 °C, 30 minð17Þ
Japanese chemists have reported an interesting dichlorination of enantiomerically pure chiralsulfide, not observing racemization at a carbon atom adjacent to the chlorinated one (Scheme 33)<2000TL4603>.
Ph SO
Ph SO
Cl Cl
OS
Et
OO
SEt
O
Cl Cl
OS
O
O O
OS
O
O O
Cl Cl
PhS
O
O
PhS
OCl
O
Cl
S
O
S
O
Cl Cl81%
SO2Cl2, CH2Cl2
96.5%
SO2Cl2, CH2Cl2, 20 °C, 2 h
SO2Cl2, CH2Cl2
81.5%
SO2Cl2, CH2Cl2
88.5%
72.5%
SO2Cl2, CH2Cl2
Scheme 31
Ph SF
FF
Ph SF
FF
Cl Cl
n-C3F7S Pr n-C3F7
S Pr
Cl Cl
FS
Et
F F
FS
Et
F F
Cl Cl
90%
SO2Cl2, CH2Cl2, 2 h
88%
SO2Cl2, CH2Cl2, 2 h
85%
SO2Cl2, Cl2HCCH2Cl, ambient temp. 2 h
Scheme 32
38 Functions Containing Halogens and Any Other Elements
Gaseous chlorine was applied for �,�-dichlorination of sulfide in methylene group activated byelectron-withdrawing methanesulfonyl moiety <1997AJC683>. Gaseous chlorine is also easilyadded to �,�-unsaturated sulfides. The addition can be followed by the replacement of a hydro-gen atom (Scheme 34) <1998ZOR1792>, alkylthio- or alkyl-groups by additional chlorine atoms(Scheme 35) <2002IZV(6)948>.
Phosphorus pentachloride was used for unsymmetrical dichlorination of bis(benzoylmethyl)sul-fide (Equation (18)) <1995ZOR1257>.
PhS
Ph
O O
PhS
Ph
O O
Cl Cl
43%
PCl5, CH2Cl2 ð18Þ
Trifluoromethylation of organic halides with FO2SCF2CF2OCF2CO2K in DMF at 45 �C wasreported <1996JFC(78)177>.�-Chlorinated-�-fluorinated sulfides are synthesized in good yields by nucleophilic fluorination
of the corresponding dichlorosulfides. It can be achieved, e.g., with Et3N–3HF in refluxingacetonitrile <1996TL2413, 1997T12565>. Also chlorination of �-fluorinated sulfides usingSO2Cl2 leads to the formation of chloro-�-fluorosulfides, sometimes in very high yields(Schemes 36 and 37) (Table 1).
Ph SO
F F
F
O
Ph SO
F F
F
O
Cl Cl100%
SO2Cl2, CH2Cl2, 20 °C, 3 h
Scheme 33
SS
ClCl
Cl ClCl
68%
Cl2, CCl4, 10 °C, 2.5 h
Scheme 34
ClS
Cl
CO2F3C Cl
ClBn
SS
Bn
CO2F3C
49%
Cl2, –78 to –50 °C, 29 h–
–
Scheme 35
RS CO2Me R
S CO2Me
Cl ClR
S CO2Me
Cl F
RS CO2Me
FR
S CO2Me
Cl F
R = Ph, Me, CO2Me
ca. 100%
2SO2Cl2
R = Ph 42%, Me 37%, CO2Me 75%
PH2F3, CCl42SO2Cl2
Scheme 36
Functions Containing Halogens and Any Other Elements 39
(ii) From halofluoroalkanes and derivatives
The extensive studies on photochemical reaction of fluoroiodoalkanes with both methyl sulfide anddimethyl disulfide were reviewed earlier in <1995COFGT(6)35>. Photochemical substitutionreaction of fluoroiodoalkane by thiole anion has recently been performed, leading to the corre-sponding sulfide in a high yield (Scheme 38) <1998SL1243, 2001JFC(108)95>.
Several recent reports bring examples of the nucleophilic substitution of 1-iodoperfluoroalkanes bythiols carried out in the absence of irradiation (Scheme 39) <1995JFC(74)123, 1998MI(8)1193,1997JOC1457, 1995JOC6186>. Reactions of derivatives of ethyl difluoroiodoacetate with thioleanions either pre-generated or formed in situ are also known (Scheme 40) <2002TL2949>.
Terminally iodinated perfluorohexane reacts with a derivative of 2-naphthothiol in dimethylformamide in the presence of sodium ethanolate at room temperature to give the expected sulfide(Equation (19)) <1999CC2007, 2002JPCA3114>. S-(Perfluorooctyl) thioglycoside derivative canbe obtained in a similar way under the different reaction conditions (Equation (20))<1999JFC(98)55>.
R
R'S A
R
R'S A
Cl ClR
R'S A
Cl FEt3N–3HF2SO2Cl2
Scheme 37
Table 1 Substituents and yields of products depicted in Scheme 37
R R0 A Yield (%)
25 �C, 15–24 hPh H CO2Me 67Me H CO2Me 78MeCO2 H CO2Me 56Ph H COMe 41Me H COPh 67Me Me COPh 54Ph H CN 0
180 �C, 24–36 hPh H CO2Me 77Me H CO2Me 70Ph H COMe 65Me H COPh 70Me Me COPh 57Ph H CN 50Me Me CO2Me 57
HS OEt
O
S OEt
O
n-C8F17
Sn-C6F13
79%
RSH, liq. NH3, UV n-C6F13I
RSH =
83%
RSH, liq. NH3, UV n-C8F17I
OEt
O
Scheme 38
40 Functions Containing Halogens and Any Other Elements
O OPriO
n-C6F13-S-Ar
Ar =
ArSH, EtONa, DMF, rt, 24 hn-C6F13I
ð19Þ
O
AcO
OAc
OAc
OAc
n-C8F17SR
R =
DMF, H2O, 20 °C, 1.5 h
RSH, NaHCO3, Na2S2O4n-C8F17I
ð20Þ
Reaction of 1-iodoperfluorobutane with propane-1,3-dithiol occurs under very mild conditions.Both thiol groups react, affording a moderate yield of the corresponding sulfide (Scheme 41)<2000JFC(105)41>.
benzene, rtPhSH, DBU
50%
n-C8F17-S-Phn-C8F17I
n-C8F17I benzene, rt, 15 h
p-MeC6H4SH, DBU
60%
n-C8F17-S-C6H4Me-p
NaH, DMF, rt, 24 h
p-HOC6H4SH
30%n-C4F9-S-C6H4OH-pn-C4F9I
NaH, DMF, rt, 24 h
p-MeC6H4SH
77%p-MeC6H4-S-C4F9n-C4F9I
ii. DMF, rt, 2 h
i. NaH, DMF, rt, 1 hn-C8F17I
p-BrC6H4SH
p -BrC6H4-S-C8F17
Scheme 39
EtO
F
FI
OPri
SO
Et
F F
O
EtO
F
FI
O
N
ArS
OEt
F F
O
Ar =
DMF, 30–40 °C, 4 h
ArSH, Et3N
DMF, 4 h, 30–40 °C
PriSH, Et3N
Scheme 40
Functions Containing Halogens and Any Other Elements 41
1,1-Difluoro-1,3-diiodoheptane in reaction with thiophenol, following its deprotonation by sodiumhydride, behaved differently producing an unsaturated sulfide (Equation (21)) <2001JFC(107)89>.
F
FI
I
F
FSPhPhSH, NaH, DMF ð21Þ
The respective sulfide was produced by the nucleophilic substitution of a bromine atom,in bromodifluoromethyl group attached to benzoxazole moiety, using 2-thiopyridone anion(Equation (22)) <2000JFC(102)369, 2001JFC(109)39>.
N
O F
FBr
NHS
N
O F
FS
N, NaH
DMF, rt, 23 h
ð22Þ
Novel styrene and dimethylisophthalate monomers, with pendant lithium fluoroalkylsulfonateor sulfonimide functional groups and containing perfluoroalkyloxy substituents, were preparedfrom the corresponding phenolic intermediates. Necessary formation of CF2�S fragment wasachieved by substitution of bromine atom in a terminal CF2Br group by SO2Na anion (Scheme 42)<2000JFC(105)129>.
(iii) From a,a-dichloroalkyl sulfides
Dichloroalkyl sulfides are convenient starting materials for the preparation of chlorofluoroalkyl,bromofluoroalkyl, and difluoroalkyl sulfides <1995COFGT(6)35>. Fluorination of dichloroalkyl sul-fides containing additional functional groups has been widely studied by Pommelet et al.They describedthe synthesis of alkylsulfanyldifluoroacetates and ketones by the Halex reaction. The remarkablereactivity of difluorothioacetate derivatives opened rapid access to the preparation of useful buildingblocks such as gem-difluoroketones and amides (Schemes 43 and 44) (Table 2) <2003TL5061>.
n-C4F9S SC4F9-nDMF, 15 min, 20 °C, 45%
n-C4F9I, Na3PO4HS SH
Scheme 41
H2O, 75 °C, 3 h, 97%
Na2S2O4, NaHCO3, DMFp-BrC6H4OCF2CF2SO2Nap-BrC6H4OCF2CF2Br
Scheme 42
R
R'S A
R
R'S A
Cl Cl R
R'S A
Cl F
(b)(a)
Et3N–3HF2SO2Cl2
A = CO2Me, COMe, COPh
Scheme 43
PhSF
F
CO2Me PhSF
FCOR
–78 °C, 0.5 h
RM, THF, rt
R M Yield (%)
Me Li 80H2C=CH MgBr 70H2C=CH-CH2 MgBr 82
Scheme 44
42 Functions Containing Halogens and Any Other Elements
An exchange of chlorine atom in �,�-dichlorofluoropentyl benzyl sulfide using antimonypentafluoride in acetonitrile was reported (Scheme 45) <1998ZOR1012>.
(iv) From tri- or tetrahalomethanes
Only a few examples of substitution of a chlorine atom in chlorodifluoromethane by thiols, using avariety of conditions, have been reported in <1995COFGT(6)35>. A mechanism of the substitutionhad been under discussion pointing to both a carbene and SN2 type character. Since then many newsyntheses of dihaloalkyl sulfides have been published. Such methane derivatives like difluorodi-iodomethane, chlorodifluoromethane, trifluoro-, and trichloromethanes were applied as startingmaterials. It appears from these reports that the carbene mechanism predominates.
The treatment of difluorodiiodomethane with thiophenol in the presence of sodium hydrideaffords difluoromethyl phenyl sulfide in a low yield (Equation (23)) <2000JFC(102)105>.
FF I
I
F
FSPh
12%
PhSH, NaH, DMF, 20 °C ð23Þ
The majority of reported syntheses starts from chlorodifluoromethane. A high yield of therespective sulfide is obtained while treating chlorodifluoromethane with ethoxycarbonyl-methylthiol in the presence of sodium ethanolate in ethanol (Scheme 46) <2000CPB509>. Alsothiophenol reacts smoothly with chlorodifluoromethane, this time in the presence of sodiumhydroxide in aqueous dioxane (Scheme 47) <1996IZV(45)162>.
Table 2 Substituents and yields of products depicted in Scheme 43
R R0 Product (a) yield (%) Product (b) yield (%)
Ph CO2Et 52 70Bz CO2Me 70 52MeO2CCH2 CO2Me 75 75AcO(CH2)2 CO2Me 80Et COPh 70 61Bz COMe 65 72Ph COMe 68Ph COPh 54
F S Ph
Cl Cl
F F
F F
F F
F
F Ph
F Cl
F F
F F
F F
FSbF5, MeCN, ∆,1 h
56% S
Scheme 45
F
FCl
F
FSCH2CO2Et
80%
EtOH, 1 h, heat
EtOCOCH2SH, EtONa
Scheme 46
F
FCl
F
FSAr
89%
dioxane, H2O,
45 °C, 3.3 h
Ar = C6F5
ArSH, NaOH
Scheme 47
Functions Containing Halogens and Any Other Elements 43
Heteroaromatic thiols can substitute a chlorine atom in chlorodifluoromethane. An example ofthis type of reaction is reported to give the respective sulfide in a low yield (Scheme 48)<2001JFC(108)211>. A similar method was used for the preparation of a sulfide containing,beside difluoromethyl group, a large chiral substituent (Equation (24)) <1998JAN374>.
F
FCl
F
FSR
N
O O C6H4NO2-p
SH
OSi
RSH =
RSH
ð24Þ
Another enlarged substituent was introduced into a prepared sulfide in the presence of potas-sium t-butoxide. The reaction was carried out in tetrahydrofuran (Equation (25))<1996JMC757>.
F
FCl
F
FSR
O
O
OO
SH
H
H
RSH =
RSH, t-BuOK, THF, 0 °C, 30 min
ð25Þ
Only one example of sulfide formation starting from trifluoromethane has been found. Dioctyldisulfide was used in the reaction as a precursor of an attacking S-nucleophile (Scheme 49)<2000JOC8848>.
Also only one example of synthesis of sulfides starting from trichloromethane has been spotted.The reaction was performed under PTC conditions and doubtlessly followed the carbene mechan-ism resulting in insertion of dichloromethylene between sulfur atom and vinyl group (Scheme 50)<2000CHE201>.
F
FCl
F
FSAr
N
NEtO
24%
DMF, 50–120 °C, 5 min
Ar =
ArSH, KOH, DMF
Scheme 48
FF
Fn-C8H17S
F
FMe3SiSiMe3, DMF, THF
–15 to –20 °C, 17.5 h45%
n-C8H17SSC8H17-n
Scheme 49
44 Functions Containing Halogens and Any Other Elements
(v) From thioformates, thioesters, and ortho-trithioesters
COFGT (1995) <1995COFGT(6)35> has brought only examples of dichlorination of alkyl thio-formates yielding alkyl dichloromethyl sulfides. Since then several new approaches to the synthesisof dihaloalkyl sulfides have been designed starting with dithioesters or ortho-trithioesters.
(a) From dithioesters. Thiocarbonyl group in dithioesters can be exchanged by difluoremethy-lene moiety using mercury(II) fluoride–potassium fluoride mixture in tetrahydrofuran in thepresence of pyridinium hydrogen fluoride (Equation (26)) <1996TL3223>.
PhS
S
PhS
F F
HF–pyridine
HgF2, KF, THF ð26Þ
Similar results (the exchange of sulfur atom by two fluorine atoms) were achieved usingtetrabutylammonium–hydrogen fluoride complex in the presence of N-iodosuccinimide (Scheme51) <1999BCJ805> or by treating dithioester with bis(2-methoxyethyl)aminosulfur trifluoride inthe presence of antimony(III) fluoride (Scheme 51) <2000JOC4830>.
(b) From ortho-trithioesters. In 1998, Japanese chemists published two papers on synthesis of�,�-difluoroalkyl sulfides from ortho-trithioesters. The use of Et2SF3 led to the formation of thedesired sulfide in a very low yield <1998BCJ2687>. In contrast to that, the same authorsachieved very good results of difluorination, applying tetrabutylammonium–hydrogen fluoridecomplex in the presence of 1,3-dibromo-5,5-dimethylhydantoin (Scheme 52) <1998BCJ1939>.
(vi) From alkenes
The first report on synthesis of dichloroalkyl sulfides via chloroalkenes was probably published in1958. Since then additions of thiols or disulfides to alkenes have been reported several times<1995COFGT(6)35>. In the last few years haloalkenes became rather common substratesin syntheses of dihaloalkyl sulfides. Several haloalkenes such as tetrafluoroethene, chlorotri-fluoroethene, alkoxytrifluoroethene, 1,1,2-trifluoroalkenes, 1,1-dichloro-2,2-difluoroethene, and1,1-difluorethene were used in reactions with thiols, disulfides, or other sulfur compounds toyield difluoroalkyl sulfides.
p-Ph-C6H4
S
Sp-Ph-C6H4
S
FF
S
SS
F F
p-(t-Bu)C6H4
S
Sp-(t-Bu)C6H4
S
FFbis(2-methoxyethyl)aminosulfur trifluoride
SbCl3, CH2Cl2, 20 °C,1 h
N-iodosuccinimide, BunN–H2F3, CH2Cl2
52%
N-iodosuccinimide, Bun4N–H2F3, CH2Cl2
86%
74%
4
Scheme 51
Cl
ClCl
N
NS
N
NS
Cl Cl
21%
TBAB, NaOH aq. 50%45–55 °C, 25 h
H
H
Scheme 50
Functions Containing Halogens and Any Other Elements 45
Reaction of tetrafluoroethene with sulfur chloride leads to the formation of mixtures ofcompounds in proportions depending on the conditions used. One of the products is shown inEquation (27) <2001JFC(112)325>.
F
F
F
F
FS
SClF
F
F F
and others
40 °C, 12 h
S2Cl2, HF, BF3
ð27Þ
Irradiated 1,1,2-trifluoro-1,4-pentadiene reacts smoothly with mercaptoacetic acid. A high yieldof the addition of two molecules of the nucleophile to both double bonds is observed. When thereaction is conducted in the presence of azobisisobutylnitrile, an initiator of a radical process, theyield drops down (Scheme 53) <1998JFC(92)77>.
Sodium thiophenolate is added easily though slowly to chlorotrifluoroethene in ethanol afford-ing 2-chloro-1,1,2-trifluoroethyl phenyl sulfide <1997T17127, 1998TL6529>. At higher tempera-tures the reaction proceeds faster without affecting a yield (Scheme 54) <2000T3539>.
Products distribution in reactions between chlorotrifluoroethene, 1,1-difluoroethene andethylene thioglycol has been studied in detail. One of the major products is 2-chloro-1,1,2,4,4-pentafluorobutyl 20-hydroxyethyl sulfide (Scheme 55) <1995JFC(74)37>.
S
SS
OH
Ph
S
SS
O
PhF
FS
O
Ph
PhS
SS
PhF
FS
Br
PhF
FS
O
OS
SSPh O
F
FSPh
F
i = 1,3-dibromo-5,5-dimethylhydantoin
51%
Bu4N–H2F3, i. CH2Cl2, 10 min
62%
Bu4N–H2F3, i. CH2Cl2, 10 min
79%
Bu4N–H2F3, i. CH2Cl2, 20 min
Bu4N–H2F3, i. CH2Cl2, 10 min
51%
Et2NSF3, CH2Cl2, 0 °C, 10 min
13%F
FSPh
O
PhS
SS
OH
Scheme 52
F
F F
OS
S
HO
F F O
OH
F
F F
OS
S
HO
F F O
OH80 °C, 7 h, 37%
HO2CCH2SH, AIBN, MeCN
irradiation, 81%
HO2CCH2SH, MeCN, PhCOPh
Scheme 53
46 Functions Containing Halogens and Any Other Elements
Chlorotrifluoroethene forms the respective chlorotrifluoroethyl phenyl sulfide in reaction withdiphenyl disulfide under electrochemical conditions. The yield of the product is reasonable(Equation (28)) <1998CCC378>.
F
F
F
ClPh
SCl
F F
F
PhSSPh, MeCN
Electrolysis, 30% ð28Þ
Fluorosulfonic acid and sulfur dichloride reacting with trifluoromethyl trifluorovinyl ether yielda product containing fragments of both reagents added to the double bond in the starting ether(Equation (29)) <1996IZV(7)1745>.
F
F
F
OF
FF
FS
OS
ClF F
F O F
FF
O O32.5%
SCl2, HSO3F, 30–35 °Cð29Þ
Several new examples of addition of thiols to 1,1-dichloro-2,2-difluoroethene have beenreported. The reaction is highly regiospecific, leading to the formation of �,�-difluoro-�,�-dichloroethyl sulfides usually in very good yields (Scheme 56) <1995JFC(73)27, 2000T3539>.
When N-(t-butylcarboxy)-2-thiopyridone (instead of a thiole) is added to dichlorodifluoro-ethene, the reaction of addition is accompanied by migration of the N-substituent, and�,�-difluoro-�,�-difluoroalkyl 2-pyridyl sulfides are obtained (Scheme 57) <1992TL3491,1995T1903, 1997JOC7192>.
F
F
F
Cl
PhS
ClF F
F
F
F
F
Cl
PhS
ClF F
F
PhSH, NaOH, 120 °C, 6 h
76%
PhSNa, EtOH, 15 h
85%
Scheme 54
F
F
F
F
Cl
HOS
F
F
F F
F ClMeCN, 80 °C, 4 h
HOCH2CH2SH, Bz2O2
Scheme 55
F
F
Cl
Cl
n-C6F13CH2CH2SCl
F F
Cl
F
F
Cl
ClPh S Cl
F F
Cl
90%
PhSH, NaOH, 120 °C, 8 h
Butperpivalate, 70 °C, 4 h
n-C6F13CH2CH2SH, MeCN
Scheme 56
Functions Containing Halogens and Any Other Elements 47
Novel sulfides, sulfones, and fluorovinyl ethers were prepared using tetrafluoroethylene as theonly fluorinated substrate. Addition of thiole sodium salts and carbon dioxide to tetrafluoroethy-lene, followed by dimethylsulfate, provided corresponding methyl sulfide-esters. Reduction of thesulfide-esters by sodium borohydride gave sulfide-alcohols. Oxidation of the sulfide-esters with HOFin acetonitrile resulted in the formation of the corresponding sulfone-esters. Conversion of thesulfide-alcohols to their sodium salts with sodium hydride in diglyme, followed by the addition totetrafluoroethylene, provided sulfidetrifluorovinyl ethers. The latter readily co-polymerizedwith tetrafluoroethylene to give higher molecular weight co-polymers (Scheme 58)<1999JFC(93)93>.
(vii) From carbon disulfide
Elemental fluorine reacting with carbon disulfide at �120 �C affords fluorinated sulfide. Nofurther advances have occurred in this area since the work of Shimp and Lagov <1977IC2974>cited in <1995COFGT(6)35>.
(viii) From a-fluoroalkyl sulfoxides
One example of Pummerer-type reaction was reported in <1995COFGT(6)35>. No furtheradvances have occurred in this field since that publication.
F F
F FS
F
F
F
F
O
OR S
F
F
F
F
OHR
SF
F
F
F
O
OR
O
O
RSF
F
F
F
OHRS
F
F
F
F
OCF=CF2
R = Me, But ~60%
ii. F2C=CF2
i. NaH, diglyme
MeCN, 80%
HOF
EtOH
NaBH4
R = Me 80% >90%R = But 84% >90%
ii. (MeO)2SO2
i. RSNa, CO2, DMSO
Scheme 58
F
F
Cl
Cl
N
S
Cl Cl
F F
But
N
S
O O
But
F
F
Cl
Cl
N
S
Cl Cl
F F
N
S
O
Oi =
35%
i. CH2Cl2, irr. 5 h
i =
52%
i. MeCN, irr.
Scheme 57
48 Functions Containing Halogens and Any Other Elements
(ix) From perfluoroalkanecarboxylic acid salts
Diphenyl disulfides react with potassium salts of perfluoroalkanecarboxylic acids at elevatedtemperatures affording moderate yields of perfluoroalkyl phenyl sulfides (Scheme 59)<2001JFC(107)311>.
6.02.1.2.2 Tetracoordinated carbon atoms bearing mixed halogens and one sulfur function(R1CHal2SR
2)
Thiolate additions to mixed chlorofluoroalkenes under radical, ionic, or electrochemical condi-tions were employed to prepare mixed dihaloalkyl sulfides <1995COFGT(6)35>. As one can seefrom examples shown here (in equations and schemes), the reactions used resemble thosedescribed in the former section of this chapter. Fluorination of chloroalkyl sulfide has beenreported too (Equation (30)) <1995JOC3459>.
Ph S CO2Et
Cl
Ph S CO2Et
Cl F
Electrolysis, 66%
Et3N–3HF, MeCN, 20 °C ð30Þ
Pommelet et al. elaborated several reactions leading to mixed dihaloalkyl sulfides(Scheme 60) <1996TL2413>. Particularly interesting is the practically quantitative, highlyregiospecific chlorination of methyl esters of �-alkylthio-�-fluoroacetic acid, using sulfuryldichloride.
�-Chlorinated-�-fluorinated sulfides were synthesized in good yields by the nucleophilic fluor-ination of the corresponding dichlorinated sulfides, formed in the first step of the reaction. It canbe achieved with Et3N-3HF in refluxing acetonitrile. A number of examples are given in thescheme-explaining table (Scheme 37, Table 1) <1997T12565>.
Addition of cysteine N-acetyl derivative to 1,2-dichloro-1,2-difluoroethene in the presence ofsodium amide at �50 �C occurred without racemization (Equation (31)) <1996MI1092>.
RS CO2Me R
S A
Cl Cl RS A
Cl F
RS CO2Me
FR
S A
Cl F
OS
O
O
F
O
OS
O
O
F
O
Cl
OS
O
O OO
OS
O
O
F
O
SbCl3, DAST, rt, 2–3 d
SO2Cl2
R = Ph, Me, CO2Me
ca. 100%
2SO2Cl2
R = Ph 42%, Me 37%, CO2Me 75%
CCl4
PH2F32SO2Cl2
Scheme 60
PhSC3F7-n29%
PhSSPh, DMF, 130 °C, 6 hn-C3F7COOK
42%
PhSSPh, DMF, 145 °C, 5 hPhSC2F5C2F5COOK
Scheme 59
Functions Containing Halogens and Any Other Elements 49
F F
Cl ClCO2H
SH
HAcHN
CO2H
S
HAcHN
Cl
F Cl
F
RSH =
RSH, NaNH2, liq. NH3, –50 °C
ð31Þ
6.02.1.2.3 Tetracoordinated carbon atoms bearing one halogen and two sulfur functions(R1CHal(SR2)2)
No further advances in the field of the title compounds synthesis have occurred since thepublication of COFGT (1995) <1995COFGT(6)35>. Only an interesting transformation of acompound of this class was reported (Equation (32)) <1996CB1383>.
(F3CS)2CBrCO2SiMe383%
Me3SiCl, 50 °C, 6 h (F3CS)2CBrCO2H ð32Þ
6.02.1.3 Halogen and Se or Te Derivatives (R1CHal2SeR2 or R1CHal2TeR
2)
6.02.1.3.1 Tetracoordinated carbon atoms bearing two halogens and one selenium function(R1CHal2SeR
2)
Several examples of compounds of the type reviewed in this section have been reported. Theirpreparation often involves transmetallation reactions of metal selenyl dihalomethyl derivatives.Also numerous examples of organoselenium metal complexes are known. In some cases almostquantitative yields of the products are obtained. Sometimes mixtures of organoselenium com-pounds are produced and neither the conditions of reactions nor yields are provided<1995COFGT(6)35>. Some advances that have occurred in this field since the publication ofCOFGT (1995) are presented here.
(i) From difluoroiodoalkane, bromodifluoroalkane, or chlorodifluoroalkane derivatives
Twelve years ago Uneyama and Kitagawa reported shortly that butylphenyl selenide togetherwith other products can be obtained by reaction of (nanofluorobutyl)iodide with diphenyldiselenide (Equation (33)) <1991TL375>. Ten years later the same method, under modifiedconditions, was applied for the preparation of perfluoroalkyl phenyl selenides in high yields(Scheme 61) <2001SL1260>.
NaBH4, PhSeSePh, EtOH, 0 °C, 15 minC4F9SePh
rt, 2 h, 1-hexeneC4F9I ð33Þ
n-C8F17SeMeMeSeSeMe, NaO2SCH2OH, DMF, H2O, 20 °C
79%n-C8F17I
n-C4F9SePh57%
PhSeSePh, NaO2SCH2OH, DMF, H2O, 20 °Cn-C4F9I
Scheme 61
50 Functions Containing Halogens and Any Other Elements
Bis(Pentafluoroethyl)selenide has also been formed from pentafluoroethyl iodide and seleniumin the presence of copper metal (Equation (34)) <2000JFC(102)301>.
C2F5SeC2F5Se, Cu, 220–230 °C, 15 h
C2F5I ð34Þ
Irradiation of mixtures of �-chloro-�,�-difluorotoluene with sodium arylselenolates in dimethylformamide results in the formation of aryl �,�-difluorobenzyl selenium (Scheme 62)<1996BCJ2019>.
Reaction of N-allyl bromodifluoroacetamide with bis(phenyl)diselenide results in the substitutionof a bromine atom by phenyl selenide group (Equation (35)) <1997TL7763>.
NF
FBr
O
NF
FSe Ph
O
45%
PhSeSePh, NaBH4, THF, EtOH, 0 °C, 3 h
H H
ð35Þ
(ii) From 1,1-difluoroalkene derivatives
Chlorotrifluoroethene reacting with bis(phenyl)diselenide in acetonitrile under electrochemicalconditions affords 2-chloro-1,1,2-trifluoroethyl phenyl selenide in a good yield (Equation (36))<1998CCC378>.
F
F
F
Cl
Ph SeF
F
F
Cl57%
PhSeSePh, MeCN, electrolysis ð36Þ
Selenium compounds can be added to the double bond of 1,1-difluoroethene derivativesbearing a variety of additional substituents (Scheme 63) <2000TL7893, 2002CEJ2917>.
A mixture of reduced products containing �,�-difluoromethyleneselenium moiety is obtainedin the reaction of difluoromethyl phenyl selenoxide with dimethyl sulfide and acetic anhydride indichloromethane. Similar reductions, unfortunately also leading to very low yields of difluoro-methyl phenyl selenide, are observed in reactions of the selenoxide with mixtures of e.g.,BuOBu�Ac2O, MeOCH2CH2OMe�Ac2O, (CH2)3O�Ac2O, (CH2)5O�Ac2O, etc. (Scheme 64)<1995JOC370>.
PhF
FCl Ph
F
FSe Ar
Ar = Phenyl, 89%; naphthyl, 84%
Irradiation
ArSeNa, EtOH, DMF, 100 °C
Scheme 62
p-MeOC6H4 NSiMe3
F
FEtO2C
p-MeOC6H4 N F
FEtO2CSePh
Ph NN
O
F
FPh N
N
O
F
F
Se Phii. H2O, hexane, THF, 1 h, 60%
i. PhSeCl, TfOSiMe3, hexane, THF, 20 h
64%
PhSeF, CH2Cl2, –78 °C
Scheme 63
Functions Containing Halogens and Any Other Elements 51
6.02.1.3.2 Tetracoordinated carbon atoms bearing two halogens and one tellurium function(R1CHal2TeR
2)
Among compounds described in this section only perfluoroalkyl tellurides and additionallyditellurides have been well known for more than ten years. Other compounds of this class havehardly been reported and without details of their preparation or yields obtained. The 1990s havebrought about more details concerning preparations of difluoroalkyl tellurides. A general route tothese compounds involves the reaction of dialkyl tellurides with bis(trifluoromethyl) cadmium ortrifluoromethylzinc bromide performed in the presence of acetonitrile and boron trifluoride<1995COFGT(6)35>. Some advances that recently have occurred in this area are presented here.Unfortunately, the examples concern only syntheses of perfluoroalkyl derivatives of tellurium.
Bis(pentafluoroethyl)telluride was obtained by the treatment of pentafluoroiodoethane withtellurium in the presence of copper metal at a very low pressure and an elevated temperature.Bis(pentafluoroethyl)ditellurid was prepared in a high yield under similar conditions usingbis(pentafluoroethyl)mercury as the starting material (Scheme 65) <1996JCS(D)4463>.
UV-irradiated bis(pentafluoroethyl)telluride is transformed into bis(pentafluoroethyl)ditellur-ide, which on treatment with silver cyanide gives (pentafluoroethyl)tellurium cyanide and withmolecular iodine at low temperature yields (pentafluoroethyl)tellurium iodide (Scheme 66)<2000JCS(D)11>.
6.02.1.4 Halogen and Mixed Chalcogen Derivatives (R1CHal(OR2)(SR3))
These compounds have been practically excluded from this section because the system is almostexclusively present in heterocycles, e.g., in oxathiolium salts covered by other reviews. Here only acouple of examples of compounds that can be described by the formula (R1CHal(OR2) (SR3)) are given.
C2F5TeTeC2F5C2F5HgC2F585%
Te, Cu, 200 °C, 15 h
C2F5TeC2F568%
Te, Cu,180 °C,36 h, 0.01 torrC2F5I
Scheme 65
n-C3F7TeC N
I2, CHCl3, –196 to –20 °Cn-C3F7TeI
100%n-C3F7TeTeC3F7-n
AgCN, 22 °C
92%n-C3F7TeTeC3F7-n
n-C3F7TeTeC3F7-nFuran, 20 °C, 16 h, UV
73%n-C3F7TeC3F7-n
Scheme 66
Ph SeF
F
OPh Se
F
F
Ph SeF
F
OPh Se
F
F
S
6%
SMe2, Ac2O, CH2Cl2, ∆, 4 h
29%
SMe2, Ac2O, CH2Cl2, ∆, 4 h
Scheme 64
52 Functions Containing Halogens and Any Other Elements
In 1995 Chande and Joshi published two papers describing bromination of extended ethanonederivatives, bearing C-, O-, S-linked large substituents and a hydrogen atom at the �-carbon atom.Solutions of the starting material and molecular bromine in glacial acetic acid, when subjected toultraviolet irradiation, afford products. Yields of the bromination products, depending on substi-tuents in a substrate, vary from 50% to 95% (Scheme 67) <1995IJC(B)54, 1995IJC(B)147>.
6.02.2 FUNCTIONS CONTAINING HALOGEN AND A GROUP 15 ELEMENTAND POSSIBLY A CHALCOGEN
6.02.2.1 Halogen and Nitrogen Derivatives: General Considerations
Compounds of this class are somewhat unstable, being in equilibrium with the correspondingisomeric haloiminium salts. The equilibrium between isomeric forms depends on N-substituents.Electron-withdrawing substituents shift the equilibrium to haloalkylamines. This dynamic balancehas been discussed in several papers and reviews <1995COFGT(6)35>.
6.02.2.1.1 Tetracoordinated carbon atoms bearing two halogens and one nitrogen function
Similar to COFGT (1995) <1995COFGT(6)35>, examples described here refer to compounds forwhich the equilibrium is probably shifted to covalent species. Probably the first compoundreported as N-(dichloromethyl)-N,N-dimethylamine in US patent in 1955 did not satisfy theserequirements <1955USP2854458>.
(i) From imines
The addition of dihalocarbenes to imines was and still is a route of choice for synthesis ofheterocycles like 2,2-dihaloaziridines. No further advances have been noticed in this field sincethe publication of COFGT (1995) <1995COFGT(6)35>.
N
N
N
N
S
Ph
SPh
O C6H4Cl-p
O
C6H4Cl-p
BrN
N
N
N
S
Ph
SPh
O C6H4Cl-p
O
C6H4Cl-p
N
N
N
N
S
Ph
O C6H4Me-p
O
C6H4Cl-p
N
N
N
N
S
Ph
O C6H4Me-p
O
C6H4Cl-p
Br
N
N
N
N
S
Ph
O C6H4Me-p
O
C6H4Cl-p
N
N
N
N
S
Ph
O C6H4Me-p
O
C6H4Cl-p
Br
N
N
N
N
S
Ph
o-HOC6H4
O C6H4Me-p
O
C6H4Cl-p
N
N
N
N
S
Ph
o-HOC6H4
O C6H4Me-p
O
C6H4Cl-p
Br
90%
Br2, MeCO2H, hν
50%
Br2, MeCO2H, hν
90%
Br2, MeCO2H, hν
95%
Br2, MeCO2H, hν
H
H
H
H
H
H
H
H
Scheme 67
Functions Containing Halogens and Any Other Elements 53
(ii) From amines or hydroxylamines
Several halogenation methods have been applied to tertiary or secondary amines or alkylaminoderivatives of other compounds. Only some of the routes lead to high yields of aminodihaloalkylproducts. Just as superior fluorination involves the use of sulfur tetrafluoride, chlorinationinvolves the use of molecular chlorine. The methods can be applied to perhalogenation of bothtertiary and secondary amines. In the latter case the halogen atom also replaces N-hydrogen<1995COFGT(6)35>. Molecular fluorine was used for perfluorination of triethylamine at a lowtemperature (Equation (37)) <1999JFC(94)157>.
(F3CF2C)3NF2, –35 to –20 °C, 14 h
Et3N ð37Þ
Some other methods sporadically give satisfying results. Displacement of chlorine by fluorineatoms is an effective approach to (difluoroalkyl)amino compounds. Using hydrogen fluoride inpentane at a low temperature allows replacement of four chlorine atoms by fluorine ones inN,N-di(dichloromethyl)aniline (Equation (38)) <1996JFC(76)95>.
N
Cl
Cl
Cl
Cl
Ph NF
FPh
F
F
79%
HF, pentane, –30 to –5 °Cð38Þ
An unusual N-perfluoroalkylation of O-benzoyl sec-butylhydroxylamine, using bis-heptafluoro-butyryl peroxide in perhalogenated ethane, leading to the formation of the correspondingamineoxy free radical, has recently been reported (Equation (39)) <2002JFC(116)109>.
NO Bz N
O
C3F7-n20 °C
(C3F7CO2)2, Cl2FCCClF2
H
ð39Þ
A common electrochemical approach usually affords mixtures difficult to separate and leads tolow yields of the desired compounds. Some exceptions to this general rule are known. Whilefluorination of N-ethyl-N-isopropyl amine under electrochemical conditions leads to a very lowyield of the corresponding perfluorinated compound, N-(n-butyl)-N-methylamine under similarconditions affords a high yield of its perfluorinated derivative (Scheme 68) <2000JFC(106)35>.The same authors have reported moderate yields of perfluorinated products in electrochemicalsyntheses of other compounds too. An example is given (Equation (40)) <2001JFC(108)215>.
N
N
OO
O O
N FF
F FF
FF
FF F FF
FF
50%
HF, 7–8 °C, 10 h, electrolysis O
F ð40Þ
N N F
FF
F
FF
F
F
FFF
FF
N NF
F
F F
F F
F F
FF
F
HF, 7–8 °C, 390 min, electrolysis
2.4%
HF, 7–8 °C, 434 min, electrolysis
high yield
H
H
Scheme 68
54 Functions Containing Halogens and Any Other Elements
As it was mentioned before, electrochemical methods usually afford mixtures. Low yieldsof fluorinated products are determined by chromatography. This can also be found out fromthe following schemes. Often yields are not reported at all and detailed synthetic procedures arenot disclosed. Examples are given in Scheme 69 <1999JFC(97)229, 1999JFC(99)51,2001JFC(108)21> and Scheme 70 <1996JCS(P1)915, 1997JFC(82)143, 1997JFC(83)1,2002JFC(115)21>.
(iii) From amides and thioamides
Many of the compounds of this class have been prepared where electron-withdrawing groups limitthe possibility of salt formation. A variety of approaches were successfully used in these cases forconversions of amides and thioamides. Some advances that have occurred in this area since thepublication of <1995COFGT(6)35> are reported here.
N,N-Dimethyl-�,�-difluorobenzylamine was prepared in a good yield from N,N-dimethyl-benzthioamide by its fluorination with bis(2-methoxyethyl)aminosulfur trifluoride in the presenceof antimonium trichloride (Scheme 71) <2000JOC4830>.
N
N
OH
(C2F5)2N
F F
O
F
(F3C)2N
F F
O
FNOSi
N
N
OH
HO
(C2F5)2N
F F
O
F
8.7% (chromat.)
HF, 7–8 °C, 616 min, electrolysis
H
8.1%
HF, 7–8 °C, 521 min, electrolysis
5.9%
HF, 7–8 °C, 637 min, electrolysis
Scheme 69
N
O
ON
O
FF F
F F FF
F
FF
F
N
F F
F
FF
F
N N
N
NN(C2F5)3
(n-C3F7)3N(n-C3H7)3N
(F3C)3N
n-C3F7N(C2F5)2
HF, electrolysis
Not separated
HF, electrolysis
HF, electrolysis
HF, electrolysis
HF, 0 °C, 24 h
Electrolysis
Scheme 70
Functions Containing Halogens and Any Other Elements 55
Very high yields of N,N-di(dichloromethyl)aniline and its p-chloro derivative are obtained fromthe corresponding N,N-diformylanilines while treating them with phosphorus pentachloride–phosphorus oxychloride mixture (Scheme 72) <1996JFC(76)95>.
The last decade has produced several examples of synthesis of N-(dihaloalkyl)sulfonamidesfrom sulfonamides. The sulfonyl group obviously stabilizes the products. Cobalt trifluoride ata high temperature allows the displacement of four hydrogen atoms by fluorine ones inN,N-dimethylamide of fluorosulfonic acid (Equation (41)) <1995JFC(74)181>.
SF NO
O
FF
FF
SF NO
O
CoF3, 200–250 °C
38.5%ð41Þ
Fluorination of N,N-dimethylamide of trifluoromethanesulfonic acid under electrochemicalconditions affords the corresponding, additionally tetrafluorinated, sulfonamide in low to mod-erate yields. Other examples of halogenation under electrochemical conditions of either sulfona-mides or amides were also reported (Scheme 73) <1995JFC(75)157, 1998JFC(87)157,1997JFC(81)115, 2002JFC(113)201>.
PhS
NPh
FN
F
bis(2-methoxyethyl)aminosulfur trifluoride
SbCl3, CH2Cl2, 20 °C, 48 h
78%
Scheme 71
N O
OPh N
Cl
Cl
Cl
Cl
Ph
p-Cl-C6H4-N O
Op-Cl-C6H4-N
Cl
Cl
Cl
Cl
92%
PCl5, POCl3, 80 °C, 2 h
94%
PCl5, POCl3, 80 °C, 2 h
Scheme 72
S NO
O
FF
FS NO
O
FF
F
FF
FF
N SO
O
F
FS NO
O
N SO
O
F
F
S NO
O
FF
FF F
F
FF
n-C3F7
O
N
n-C3F7
O
NF
FFF
HF, –15 °C, electrolysis
27%
HF, electrolysis
HF, 0 °C, electrolysis
Scheme 73
56 Functions Containing Halogens and Any Other Elements
N-Alkylation of sulfonamide sodium salt by bromodifluoroalkene is another approach to thesynthesis of an N-(�,�-difluoroalkyl)sulfonamide (Equation (42)) <2000CPB885>. The displace-ment of a sulfur atom by two fluorine ones in thioamide is shown in Equation (43) <1998SL1243>.
FBr
FF
NF SO2
Me
Ph, Pd(OAc)2, PPh3, THF, 40 °C, 2 h (PhNSO2Me) Na ð42Þ
n-C7F15
S
Nn-C7F15
F
N
FNBS, PPHF, CH2Cl2, 1 h ð43Þ
(iv) From acyl halides
Treatment of acyl fluorides with tetrafluorohydrazine under photolytic conditions resulting in theformation of corresponding perfluoroaminoalkane was reported earlier <1995COFGT(6)35>.
A perhalogenated tertiary amine, containing apart from fluoro-substituents, one iodo-atom in�-position was prepared by Abe et al. from the appropriate acyl fluoride by treating it withlithium iodide at an elevated temperature (Equation (44)) <1997JFC(83)117>.
(F3C)2NF
F
F F
OF
(F3C)2NF
F
F F
I
LiI, 180 °C, 7.3 h
63%ð44Þ
(v) From nitriles
Chlorofluorination of primary alkyl cyanides, bearing electron-withdrawing groups, is a mild andconvenient route for the preparation of N,N-dichloro- or N-chloro-N-fluoro-�, �-difluoroalkyla-mines. Yields are excellent. Other methods of synthesis of compounds of this class were alsoreported, being applied to particular cases <1995COFGT(6)35>.
The treatment of acetonitrile with hydrogen bromide for 12 days has affordedN-(�,�-dibromoethyl)-acetamidine, probably as the result of electrophilic addition of two mole-cules of hydrogen bromide to cyano group, followed by nucleophilic addition of the intermediatedibromoethylamine to another molecule of acetonitrile (Equation (45)) <1998IZV(11)2274>.
NBr N NH
Br
HBr, 12 days
H
ð45Þ
Hydrogen fluoride is added to the double N�S bond in a tetrafluorinated derivative ofacetonitrile leaving the triple C�N bond intact (Equation (46)) <1995CC1437>.
N NSF
F
F F
N NSF
F
F F Fi
i = tris(dimethylamino)sulfonium difluorotrimethylsilicateH
ð46Þ
(vi) From haloiminium salts
Haloiminium salts, by treating them with hydrogen halides at a low temperature, are easilyconverted to dihaloiminium species staying in equilibrium with dihaloalkylamines. Nothing is tobe added since the publication of <1995COFGT(6)35>.
Functions Containing Halogens and Any Other Elements 57
(vii) From haloalkenes and haloalkanes
The addition of secondary amines to perhalogenated ethenes results in the formation ofthe corresponding N,N-dialkyl-N-(tetrahalogenoethyl)amines <1995JFC(73)267, 1998JCR(M)301>.In a similar way, though under photochemical conditions, N-iodo derivatives of secondary aminesreact. The iodine atom is present in the products. Other, less general methods, were reported too inCOFGT (1995) <1995COFGT(6)35>. Since then some new examples of known methods and newapproaches to the synthesis of dihaloalkylamines from haloalkenes have been reported. For example:tetrafluoroethene reacts slowly with dimethylamine at room temperature to afford dimethyl-tetra-fluoroethylamine in 90% yield (Equation (47)) <2001JFC(109)25>.
F
F
F
F
FN
F
F FMe2NH, 20 °C, 12 h
98%ð47Þ
Secondary amines like diethylamine and di(n-butyl)amine are easily added to the double bond in anunsaturated perfluorated expanded diether in tetrahydrofuran at room temperature. Also in thesecases yields of the addition products are high (Scheme 74) <1999ZPK(72)1345, 2000JFC(106)13>.
Tetrafluoroethene reacting at 400 �C with nitrogen trifluoride in the presence of caesiumfluoride gave perfluorinated ethylamine in 10% yield only (Equation (48)) <2000JFC(101)15>.
F
F
F
F
NFF
FF
F F
FNF3, CsF, 400 °C, 1.5 h
10%ð48Þ
A rather unexpected product was obtained from the reaction of partly fluorinated unsaturatedtertiary amine with molecular fluorine. The reaction yielded a product, in which fluorine atomsdisplaced all hydrogen atoms in saturated N-alkyl groups while the former double bond wassaturated by addition of two hydrogen atoms or stayed intact. No yield was given (Equation (49))<1996JFC(76)139>.
(F3C)2C-CC2F5CF3
F
NEt2 (F3C)2C-CC2F5CF3
F
N(C2F5)2F2
F F F. ð49Þ
Perhaloalkanes bearing an iodine atom in one terminal position react with nitrosobutane toyield the corresponding N-perhaloalkyl-N-(t-butyl)amineoxy free radicals (Scheme 75)<1995JFC(75)1>. N-(�,�-Difluoroalkyl)-N-(t-butyl)amineoxy free radical was also produced inthe reaction of nitrosobutane with methoxycarbonyldifluoromethylsulfonyl azide (Equation (50))<1995JFC(73)175>.
F OO
FF
F F
F FF
FF
FF F F
F
F F OO
FF
F F
F FF
FF
FF F F
F
F
NEt2
F OO
FF
F F
F FF
FF
FF F F
F
F F OO
FF
F F
F FF
FF
FF F F
F
F
N(Bun)282%
BunNH, THF, 20 °C
67%
Et2NH, THF, 20 °C
2
Scheme 74
58 Functions Containing Halogens and Any Other Elements
NO
ON
O
F F
O
CH2Cl2
MeO2CCF2SO2N3 ð50Þ
Zhou et al. also reported other self-spin-probing reactions, in which products containedN-(�,�-difluoromethylene)amineoxy free radical grouping (Scheme 76) <1999JFC(98)61,1986JA3132, 1999T2263>.
(viii) Routes specific to dihalonitroalkanes and dihalonitrosoalkanes
Jones and Matthews in their review <1995COFGT(6)35> describing routes to dihalonitroalkanesdivided them into three approaches depending on the starting materials such as nitromethanes,haloalkenes, and nitro alcohols and gave examples of each approach. No further advances havebeen noted in this field since that publication. Indeed, treating of diazomethane with sodiumhypochlorite afforded dichloronitromethane, but no yield was given (Equation (51))<1998MI(32)3935>.
NH2C N NO2
Cl
ClH2O
NaOCl ð51Þ
Halogenonitrosoalkanes were not reported in <1995COFGT(6)35>. The only example of a com-pound of this class found by the authors was reported in 1995. Perfluoronitrosopropane was obtainedin a very high yield from 1,2-dimethoxyethane in reaction with bis(perfluoropropyl)cadmium andNOCl (Equation (52)) <1995JFC(73)273>.
OO C3F7NO
90%
NOCl, (C3F7)2Cdð52Þ
6.02.2.1.2 Tetracoordinated carbon atoms bearing one halogen and two nitrogen functions
When the nitrogen functions are amino groups, compounds of this class are unstable and allattempts to prepare them end in the formation of corresponding haloiminium salts. Exceptionsare halodiazirines. Many examples of synthesis of these compounds have recently been reported. Allthe examples employ amidines as starting materials. Yields of halodiazirines vary from low to high.
ClF
F F
F ICl
FF F
F N
O
Bu-t
FF
FCl
F F
F F
F IF
FF
Cl
F F
F F
F NO
Bu-t
Rongalite, DMF, H2O
ButNO, NaHCO3
aq. sulfonic acid, MeCN, H2O
ButNO, (NH4)2Ce(NO3)6, NaHSO3
Scheme 75
NO2
Na
C2F5 N NO2
O
N
ON N C2F5
O
O
Cl2FCCFCl2
C2F5NO2, CH2Cl2, (C2F5)2NO
F2ClC–CFCl2
(C2F5CO2)2, 20 °C
.
Scheme 76
Functions Containing Halogens and Any Other Elements 59
Fluorodiazirines can be prepared directly from amidines (Equation (53)) <1996JA10307> orfrom the corresponding chloro- or bromodiazirines. The second approach seems to produce betteryields of the fluoroderivatives (Scheme 77) <2001JA2628>.
NH
NH2
N
N
FDMSO, pentane, 30–35 °C
12% aq. NaOCl, KF, LiF ð53Þ
Usually chloro- or bromodiazirines are produced in higher yields than fluorodiazirines obtainedby halooxidation of the same starting amidines. Preparation of benzylchloro- and benzylfluoro-diazirines from benzylamidine can serve as an example <1997TL7049, 1998JOC3010>. In recentyears the formation of chlorodiazirines with a variety of alkyl or arylalkyl substituents hasbeen reported, mainly by Moss et al. Conditions of the reactions are disclosed in the schemes(Schemes 78 and 79) <2001TL8923, 1999TL5101, 1999CC467, 1997TL4379> and in the equa-tions (Equation (54)–(57)) <1996TL279, 1996JA10307, 1999JA5940, 2001OL1439>.
p-N3C6H4
NH2
NHp-N3C6H4
NN
Br
p-N3C6H4
NN
Brp-N3C6H4
NN
F
Bun4NF, MeCN, 25 °C, 4 h
40%
DMSO, hexane, H2ONaOBr, NaBr, LiBr, 5 °C, 1 h
79%
Scheme 77
N
N
ClNH
NH2
NH2
NH
Ph
PhCl
NNPh
Ph
NH2
NHCl
NN
NH2
NH
NN
Clpentane DMSO, 30–35 °C
AcOLi, NaOCl, AcONa, H2O
NaOCl
HOCl, Graham oxidation
40%
36%
NaOCl
35%
40%
Scheme 78
NH2
NH ClN
NCl2, NaOH, MeOH, 20 °C, 40 min
56%
NaOCl, Li, MeOH
75%
H2N NH Cl NN
Scheme 79
60 Functions Containing Halogens and Any Other Elements
NH
NH2
N
N
ClDMSO, pentane, 30–35 °C
12% aq. NaOCl, NaCl, LiClð54Þ
NH
NH2
N
N
ClDMSO, pentane, 0 °C
12% aq. NaOClð55Þ
NH
NH2
N
N
Cl
DMSO, pentane, 0 °C
12% aq. NaOCl
ð56Þ
(CD3)2CNH2
Me(CD3)2C
NN
Cl
MeNaOCl, H2O
NHð57Þ
Slightly different procedures allowed Sheridan et al. to prepare 3-cycloalkyl or 3-aryl-3-chloro-diazirines in good yields (Scheme 79) <1999TL17, 1999JCS(P2)2257>.
3-Chloro-3-(p-azidophenyl)diazirine and 3-bromo-3-(20-chloro-10,10,20-trifluoroethyl)diazirinehave recently been prepared in moderate yields in dimethylsulfoxide at temperatures rangingfrom �196 to 5 �C (Scheme 80) <2001JA2628, 2002JMC1879>.
(i) Tetracoordinated carbon atoms bearing one halogen and two nitro groups (RCHal(NO2)2)
The preparation of this type of compounds was widely reviewed and discussed. They can besynthesized by halogenation of salts of dinitroalkane anions using elemental halogens, perchlorylfluorine, or hydrogen halides. Anions of halogenodinitroalkanes easily undergo further transfor-mations, e.g., addition to aldehydes. It seems that no further advances have occurred in this areasince the publication of COFGT <1995COFGT(6)35>.
(ii) Tetracoordinated carbon atoms bearing one halogen, one nitro group,and one other nitrogen function
Probably the only example of this class is ethyl azidobromocyanoacetate, already reported in<1995COFGT(6)35>.
6.02.2.1.3 Tetracoordinated carbon atoms bearing one halogen, one nitrogen,and one oxygen function
Stable compounds of this class probably do not exist. They are only formed as intermediates in,e.g., Vilsmeier alkylation. For a discussion of their shift to iminium halide salts see chapter 6.02and the references cited therein <1995COFGT(6)35>.
p-N3C6H4
NH2
NHp-N3C6H4
NN
Cl
F
Cl
F NH2
NHF
F
Cl
F
F
NN
BrDMSO, –196 to –40 °C
NaOCl, NaBr, LiBr
DMSO, hexane, H2ONaOCl, NaCl, LiCl, 5 °C, 1 h
43%
Scheme 80
Functions Containing Halogens and Any Other Elements 61
6.02.2.1.4 Tetracoordinated carbon atoms bearing one halogen, one nitrogen,and one sulfur function
Like compounds described in the previous sub-chapter, also species with tetracoordinatedcarbon atoms bearing one halogen, one nitrogen, and one sulfur function, are nearly alwaysfound in the form of the corresponding iminium halide salts. The exceptions are nitrohalosul-fides already reported in <1995COFGT(6)35>. There have not been any further advances inthis field.
6.02.2.2 Halogen and Phosphorus Derivatives
6.02.2.2.1 Tetracoordinated carbon atoms bearing two halogens and one phosphorus function,and one halogen and two phosphorus functions
The synthetic methods for preparing carbohydrates bearing a C-branched substituent of the typeCF2-Y (e.g., n-CnF2n+1) where Y=heteroatom (O, S, P) were reviewed. Examples of thesyntheses are given (Scheme 81) <2000CAR119>.
(i) From haloalkenes
The general approach to compounds of this class involves the addition of phosphines to halo-genoalkenes. The reactions can be performed either under polar or photolytic conditions. Someexamples were given in chapter 6.02 <1995COFGT(6)35>. No further advances have occurred inthis area since that publication.
(ii) From haloalkanes
The syntheses of compounds with tetracoordinated carbon atoms bearing two halogens and onephosphorus function involving reactions of haloalkanes with phosphorus derivatives were widelyreviewed in chapter 6.02 <1995COFGT(6)35>.
Another approach, consisting of the addition of lithium derivatives of dihalomethylphosphatesto carbonyl compounds, was also reviewed previously in the work by Plantier–Royon andPortella already cited here <2000CAR119>. Among others lithiation of dibenzyl P-(difluoro-methyl)thiophosphate was mentioned (Equation (58)) <1996TL2229>.
PS
OBnOBn
F
FPS
OBnOBn
F
FLi
Hexane, –78 °C
LiN(Pr
i)2 ð58Þ
OF
Fi. (RO) 2PH, octane, ∆ O
PF
FOROR
(OR)3
ii. (ButO)2, 37%
(OR)3
OO
S
OPh
F P
F
OEtEtO
O(OR)3
O Cl
S
Ph
OO
(OR)3
moderate-to-high yieldii.
i.EtO P
O
OEt
F
FLi
S
S
Scheme 81
62 Functions Containing Halogens and Any Other Elements
An interesting and effective reduction of phosphate to the corresponding dichloromethylphos-phine using lithium aluminum hydride in the presence of aluminum brought about a paper byGuillemin et al. In this work one can also find a large quantity of data concerning phosphoruscompounds (Scheme 82) <2001JOC7864>.
6.02.2.2.2 Tetracoordinated carbon atoms bearing one halogen, one oxygen function,and one phosphorus function
Compounds of this class were not reviewed in chapter 6.02 <1995COFGT(6)35>. As shown byCairns et al. they can be formed by halogenation of phosphates containing a secondary (orprimary) P-alkyl substituent (Equation (59)) <1999PS385>.
P
O
OEtOEt
EtO
EtOPO
OEtOEt
Cl
EtOEt2O
TiCl4ð59Þ
Work by Chen et al. have indicated that �-alkoxy-�-fluoroalkylphosphates undergo sometransformations in which the �-alkoxy-�-fluoroalkylphosphate group is preserved. Thus, thecompounds containing hydroxy groups at the P-alkyl chain can be silylated, sulfonated, or canundergo Mitsunobu reaction (Scheme 83) <1996TL8975, 1998JCS(P1)3979>.
6.02.2.3 Halogen and Arsenic Derivatives
6.02.2.3.1 Tetracoordinated carbon atoms bearing two halogens and one arsenic function
Two known examples of compounds of this class were already reported in COFGT (1995)<1995COFGT(6)35>. Their syntheses involve addition of organoarsenic derivatives to perfluori-nated propene <1995COFGT(6)35>.
PO
O
O
Cl
Cl
Cl
ClPH2
(MeOCH2)2O, –80 to –30 °C
AlCl3, LiAlH4
91%
Scheme 82
SiO
O P
F
OOEt
OEtHO
O P
F
OOEt
OEt
HOO P
F
OOEtOEt
OO P
F
OOEt
OEti
N
N
N
N
NH2
i =
39%
i. DEAD, Ph3P, DMF
Dowex(H+), EtOH
57%
H
Scheme 83
Functions Containing Halogens and Any Other Elements 63
6.02.3 FUNCTIONS CONTAINING HALOGEN AND A METALLOIDAND POSSIBLY A CHALCOGEN AND/OR GROUP 15 ELEMENT
6.02.3.1 Halogen and Silicon Derivatives
A variety of �,�-dihaloalkyl silanes were prepared using different routes but only some of themare more general. A few more examples of the most common syntheses disclosing detailedconditions were reported in chapter 6.02 <1995COFGT(6)35>.
A few years ago a review was published covering preparation and reactivity of perfluoroalkyland difluoroalkyl silanes <1997CRV757>. Two following references cited there appertain todifluorosilanes <1995SL717, 1997JA1572>.
6.02.3.1.1 Dichlorocarbene addition
Dichlorocarbene generated from phenyl(bromodichloromethyl)mercury adds to a variety ofsilanes, giving the corresponding dichloromethyl silanes <1995COFGT(6)35>.
6.02.3.1.2 Other additions to silanes
Addition of bromine to alkynyl silanes results in an almost quantitative formation of tetrabromo-alkyl silanes. Also addition of methylmagnesium bromide to trichlorosilyldichloromethaneleads to the formation of trimethylsilyldichloromethane. Photochemical addition of the chloro-silylradical to tetrafluoroethene affords a very high yield of the corresponding adduct. Some ofthe reported examples concern syntheses of systems containing silicon, halogen, and chalcogen(oxygen or sulfur) at the same carbon atom. Such syntheses can be accomplished, for example,starting from (methylthiomethyl)trimethyl silane <1995COFGT(6)35>.
6.02.3.1.3 Substitution of silanes by haloalkyl derivatives
Electrochemical silylation of chlorodifluoromethyl enol ethers affords the new functionalized difluoro-methyl allyl silanes on a preparative scale in good yields. These silanes react as difluoromethyl anionequivalents with electrophiles, e.g., aldehydes (Scheme 84) <1998TL3137>.
Petrov published a simple procedure for nucleophilic perfluoroalkylation of organic and inorganicsubstrates. A mixture of iodoperfluoroalkane and tetrakis(dimethylamino)ethylene is used for thenucleophilic perfluoroalkylation. The reaction of chlorotrimethyl silane and iodoperfluoroalkane/tetrakis(dimethylamino)ethylene in diglyme results in the formation of perfluoroalkyltrimethyl silanesisolated in 55–81%yield. The interaction of this systemwith organic electrophiles, such as benzoyl andbenzensulfonyl chlorides, aliphatic and aromatic aldehydes, or activated ketones, leads to the forma-tion of the corresponding condensation products in 24–62% yield (Scheme 85) <2001TL3267>.
ClCF2
R
EtO
CF2
R
EtO
Si
R = Ph, 94%R = -(CH2)2Ph, 66%
DMF, Mg/Ni electrodes
4Me3SiCl, Bu4NBr
Scheme 84
Rf = C2F5, n-C3F7, n-C4F9
RfSiMe3Diglyme, –30 °C, 2 h, 55–81%
(Me2N)2C=C(NMe2)2, ClSiMe3RfI
Scheme 85
64 Functions Containing Halogens and Any Other Elements
6.02.4 Halogen and Boron Derivatives
A review has recently appeared on perfluoroalkylborates as congeners of perfluoroalkanes<2001CCR243>. Apart from that review no interesting reports have been found in this areasince the publication of chapter 6.02 <1995COFGT(6)35>.
Compounds of this class are usually extremely unstable and probably due to this instabilitythey have not found wider applications in organic synthesis.
6.02.5 Halogen and Germanium Derivatives
Jones and Matthews in chapter 6.02 <1995COFGT(6)35> reported several examples of efficientsyntheses of compounds of this class. It seems that since then no advances in this area have beenreported. The compounds can preferably be prepared either by addition of germane halogenidesto chlorinated alkenes or by treating bis(perhaloalkyl)mercury compounds with germane halo-genides. It is worth mentioning that trihalo(perfluoroalkyl)germanium derivatives are versatilesynthetic intermediates in formation of alkyl(perfluoroalkyl)germanium products.
6.02.6 FUNCTIONS CONTAINING HALOGEN AND A METAL ANDPOSSIBLY A GROUP 15 ELEMENT, A CHALCOGEN OR A METALLOID
6.02.6.1 Halogen and Lithium Derivatives
Haloalkyllithium compounds, due to their unusual reactivity and their ability to deliver halo-methylene group to required acceptors, are commonly used in several syntheses. Very criticalaspects of their use concern solvents and reaction temperatures. Metallation of terminal iodo-fluoroalkanes with methyllithium at �78 �C in THF, followed by the addition of sulfur dioxide,results in the formation of a lithium difluoroalkylsulfinate via intermediate organolithium specieschapter 6.02 <1995COFGT(6)35>.
Rosnati, reviewing results achieved in fluoroorganic chemistry up to 1995, <1996T1> pointedto the addition of perfluoroalkyllithium to imines reported earlier by Uno et al. <1988CL729>and <1992JOC1504>. C-Lithiation of difluoromethyl group attached to phosphorus wasreported by Piettre and Raboisson (Equation (60)) <1996TL2229>.
PS
OBnOBn
F
FPS
OBnOBn
F
FLi
Hexane, –78 °C
LiN(Pri)2 ð60Þ
6.02.6.2 Halogen and Magnesium Derivatives
Transmetallation reaction between Grignard reagents and perhalogenated systems is a versatileroute to compounds of this class; e.g., arylmagnesium bromides react with 1-iodoperfluoroalkanesat low temperatures to produce perfluoroalkylmagnesium bromides, which can be used furtherwithout separation chapter 6.02 <1995COFGT(6)35>. Applications of perfluoroalkyl Grignardreagents (CnH2n+1MgX) in the synthesis of some fluorinated amines and diamines were reportedby Katritzky et al. <1997TL7015>.
Perfluoro-n-octylmagnesium bromide can be prepared with 1-bromo-1H-heptadecafluoro-octane and hexylmagnesium bromide in THF at �60 �C in 30 min <2001JOC1316>. The reactionof heptafluoropropylmagnesium bromide with sym-ketodibenzo-16-crown-5 at �78 to 20 �C inEt2O produced the corresponding alcohol in 60% yield <2000JHC1337>.
Perfluoroalkenyl ketones were obtained by reaction of perfluorometallic reagents with acylsilanes. Long-chain F-alkylations of sugar derivatives were carried out with F-organomagnesiumbromides prepared in situ from F-alkyl iodides and ethylmagnesium bromide according to themethod reported by Burton and Yang <1998T189>, or with F-alkyltrimethyl silane<1989PGE380554> in order to compare the influence of the method on the stereoselectivity.Examples are shown in the Scheme 86 <2002TL1677>.
Functions Containing Halogens and Any Other Elements 65
DesMarteau and Creager presented, at the 226th National Meetings of the American ChemicalSociety, the paper describing applications of oligomeric bis[(perfluoroalkyl)sulfonyl]imide lithiumsalts as electrolytes for rechargeable lithium batteries <2003MI36>.
6.02.6.3 Halogen and Copper Derivatives
The reaction of copper metal with 1-iodoperfluoroalkanes at an elevated temperature is knownto produce perfluoroalkylcopper(I). No further advances have occurred in this area since thepublication of chapter 6.02 <1995COFGT(6)35>.
6.02.6.4 Halogen and Silver Derivatives
An equilibrium between the mixtures of di(perfluoroalkyl)cadmium(II) with silver nitrate andforming di(perfluoroalkyl)silver(I) anion was studied in dimethyl formamide and triethylamine ata low temperature (Equation (61)) <1997JOM79>.
[Ag(CnF2n +1)2]Equilibrium
DMF or Et3N, –30 °C
Cd(CnF2n + 1)2 + AgNO3
CnF2 n +1 = CF3, CF3CF2, CF3CF2CF2, (F3C)2CF
–
ð61Þ
The formation of organometallic compounds, bearing �,�-dihaloalkyl groups, in reactions ofsilver trifluoroacetate with perhalogenated ethene, promoted by caesium fluoride, was reportedearlier. No further advances have occurred in this area since the publication of chapter 6.02<1995COFGT(6)35>.
6.02.6.5 Halogen and Zinc Derivatives
A review on Reformatsky syntheses was published a few years ago <1999JOM215>. In thisreview the use of perfluoroalkylzinc by Kitazume and Ishikawa was mentioned <1985JA5186>.No further reports have been found in this area since the publication of chapter 6.02<1995COFGT(6)35>.
6.02.6.6 Halogen and Cadmium Derivatives
Cadmium metal inserts rather easily between carbon and halogen atoms in haloalkanes to yieldorganocadmium reagents <1995COFGT(6)35>. The synthetic methods for preparing compoundsbearing substituent such as CF2-Y were reviewed. Among others an example of the synthesis viacadmium intermediate was reported (Scheme 87) <2000CAR119>.
Bis(perfluoroalkyl)cadmium reacts reversibly in organic solvents like dimethyl formamide ortriethylamine at a low temperature with silver nitrate to yield bis(perfluoroalkyl)silver anion. An
in situ
RCSiMe3
R
O
F
F
CnF2n + 1lt – rt, 77–86% CnF2n + 1CF2CF2MgBr
or CnF2n + 1CF2CF2Li
C4F9-sugar derivativeSugar
C4F9MgBr–45 °C, 0.5 h
EtMgBr, etherC4F9I
O
Scheme 86
66 Functions Containing Halogens and Any Other Elements
equilibrium of the reaction was studied (Equation (61)) <1997JOM79>. No further advanceshave occurred in this area since the publication of chapter 6.02 <1995COFGT(6)35>.
6.02.6.7 Halogen and Mercury Derivatives
Mercuric fluoride adds readily to perhaloalkenes at elevated temperatures. Perhalodialkylmercurycompounds are formed in the reaction. There have not been any further advances in this fieldsince the publication of chapter 6.02 <1995COFGT(6)35>.
6.02.6.8 Halogen and Tin Derivatives
A few typical approaches to �,�-dihaloalkyltin derivatives were reported earlier. They involve, forexample, insertion of tin(II) chloride or fluoride into iodoperfluoroalkanes, the addition ofdialkyltin hydrides to perfluorinated alkenes or transmetallation reactions <1995COFGT(6)65>
Now some more recent examples of syntheses of �,�-dihaloalkyltin derivatives are presented.The reaction of perfluoropropylmagnesium chloride (obtained from perfluoropropyl iodide andpropylmagnesium chloride), with tin(IV) chloride was reported to give tetra(perfluoropropyl)-stannane. In a similar manner perfluoropropylmagnesium chloride reacts with other tin(IV)derivatives. Yields of products are from poor to very good depending on the starting tin species(Scheme 88) <1995JOM131>.
(EtO)2PF
FBr (EtO)2P
O
F
FCdBr
Br, rt
(EtO)2PO
F
F
62%THF
CdO
Scheme 87
Me2SnBr2
46%(H2C=CH)2Sn(C3F7)2
(H2C=CH)2SnBr2C3F7MgCl
82%(C3F7)2Me2SnC3F7MgCl
19%(C3F7)4Sn
SnCl4, Et2O, –70 to –30 °CC3F7MgCl
96%H2C=CH-Sn(C3F7)2Cl
H2C=CH-SnCl3C3F7MgCl
49%MeSn(C3F7)2Cl
MeSnCl3C3F7MgCl
11%MeSn(C3F7)3
MeSnCl3C3F7MgCl
C3F7MgCl–70 °C
PrMgCl, Et2OC3F7I
Scheme 88
Functions Containing Halogens and Any Other Elements 67
6.02.6.9 Halogen and Lead Derivatives
It was reported earlier that perfluoroalkyl iodides reacting with tetramethyllead at an elevatedtemperature afford perfluoroalkyltrimethyllead in low yields. No further advances have occurredin this area since the publication of chapter 6.02 <1995COFGT(6)35>.
6.02.6.10 Halogen and Ruthenium Derivatives
Compounds described here have not been reported in COFGT (1995) <1995COFGT(6)35>.In conjunction with two other independent minor reviews of organometallic main groupfluorides <1997MI351> and f-block fluorides <1997JFC(86)121>, an extensive reviewappeared in 1997 on compounds containing carbon�metal�fluorine fragments of d-blockmetals <1997CRV3425>. For the purpose of the reviews the term ‘‘organometallic fluoride’’was used strictly to describe compounds containing fluorine�metal and carbon�metalbonds with the same metal atom. Nevertheless, at least a few examples included in the latterreview refer to preparation of compounds, which contain such structural fragment asM�CF2H where M is Ru <1997JA3185, 1994IC1476>. Me3SiCF3 reacts smoothly withRuHF(CO)(P(Bu-t)2Me) forming Me3SiF and a six-coordinated product where �-F migrationoccurred in the proposed reaction intermediate. A fluoride atom abstraction using Me3SiOTfleads to an unusual rearrangement, in which coordinated hydride migrates to the carbene,forming CF2H fragment (Scheme 89). Experimental evidences suggest that this rearrangementoccurs by a mechanism involving dissociation of one phosphine ligand. The CF2 group isreadily converted to CO by the addition of water.
6.02.6.11 Halogen and Cobalt or Nickel Derivatives
Compounds described here were not reported in <1995COFGT(6)35>. Perfluorometallacycliccompound Ni(PEt3)2(CF2)4 reacts irreversibly with BF3�OEt2 complex affording unprecedentedperfluorometallacycle with a phosphonium ylide structure. A reaction with sequence involvingextraction of fluoride ions from the coordinated perfluorometallacycle followed by quenching thecarbene species by migration of a phosphine ligand from the metal to carbon is likely (Equation(62)) <1988OM1642> acc. to <1997CRV3425>.
NiEt3P
Et3P
F F FF
FF
F F
NiF4B
Et3P
FPEt3F
F
FF
F F
BF3–OEt2
+
– ð62Þ
Fluoroalkylphosphine complexes of nickel(0) and cobalt(I) were also described. Treatmentof (cod)2Ni with dfepe [(dfepe= (C2F5)2PCH2CH2P(C2F5)2, cod=1,5-cyclooctadiene)] yields(dfepe)Ni(cod) and then (dfepe)Ni(bipy) (Scheme 90) <2003JOM65>.
Ru
H L
LOC F Ru
L
LOC F
FF
Ru
H L
LOC F Ru
H L
LOC F
FF
RuL
LOC F
FF
THF
–Me3SiF
Me3SiCF3
–Me3SiF
Me3SiOTf
Scheme 89
68 Functions Containing Halogens and Any Other Elements
6.02.6.12 Halogen and Palladium or Platinum Derivatives
The first edition of COFGT (1995) <1995COFGT(6)35> reported neither examples of palladiumnor platinum derivatives. The annual survey on transition metals in organic synthesis (covering1993) brought, among others, an example of the reaction in which, in an intermediate, thePd�CF2 bond is possibly formed (Equation (63)) <1995CCR153>.
R' RCOCF2R
I
, L4PdRCOCF2I ð63Þ
Very recently it has been announced that the reaction of (1,5-cyclooctadiene=cod)(cod)PtMe2 with one molar equivalent of C4F9I in hexane, produces the stable perfluoroalkyl-platinum (cod)PtMeC4F9 complex (Equation (64)) <2002POL2357>.
Pt PtC4F9
53%
C4F9I, N2, 12 h ð64Þ
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(dfepe)Ni(cod)Toluene, 25 °C, 24 h, 80%
dfepe(cod)2Ni
stable up to –30 °C
(dfspe)(CO)2Co(H)i. dfepe, ii. HBF4, Me2O
(CO)4CoLiEt3BH, THF
(dfspe)2Nidfepe excess, 82%
But3Al, butadiene
(acac)2Ni
(CO)8Co
Scheme 90
Functions Containing Halogens and Any Other Elements 69
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2357–2360.2002SL996 S. Gouault, J. C. Pommelet, T. Lequeux, Syn. Lett. 2002, 6, 996–998.2002T4077 K. Wu, Q. Y. Chen, Tetrahedron 2002, 58, 4077–4084.2002T5877 S. M. Riyadh, H. Ishii, T. Fuchigami, Tetrahedron 2002, 58, 5877–5884.2002TL1677 F. Chauteau, M. Essers, R. Plantier-Royon, G. Haufe, C. Portella, Tetrahedron Lett. 2002, 43,
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Functions Containing Halogens and Any Other Elements 73
Biographical sketch
Dr. Jerzy Suwinski, Prof. of Organic Chemis-try, was born in 1939, graduated in 1961,obtained his Ph.D. in organic chemistryunder Prof. C. Troszkiewicz’s supervision atSilesian University of Technology (Gliwice,Poland) in 1968. A few years later 1973/1974he joined Prof. A. R. Katritzky’s researchgroup as a postdoc. Back in Gliwice hereceived his D.Sc. degree in 1978 and lateron in 1990 a position of Full Professor ofOrganic Chemistry. As a contract professorhe lectured in Bologna, Italy (1986, 1991),Missouri Univ., USA (1994), Campinas,Brazil (1995), Poznan, Poland (1997) and asvisiting professor also in other countries. Hismain research interest is concernedwith reactionmechanisms and nitrogen heterocycles. He isauthor or co-author of over 130 papers, books,and textbooks for students.
Dr. Krzysztof Walczak, Associate Professor ofOrganic Chemistry, was born in 1955, gradu-ated in 1980, and obtained his Ph.D. degree inOrganic Chemistry at the Silesian Universityof Technology (Gliwice, Poland) in 1988under Professor J. Suwinski’s supervision.He continued his scientific education as apost-doctoral fellow (1989–1991) at theOdense University (Denmark) with ProfessorE. B. Pedersen. In 1996 he was granted a six-month fellowship founded by the RectorsConference of Danish Universities and joinedagain Professor’s Pedersen research group atOdense University. In 1999 he received D.Sc.degree. Since then he remains at STU withexception of two sabbaticals: at the UtahState University in Logan (USA) with Profes-sor Lance Seefeldt and in Nucleic Acids Cen-tre of University of Southern Denmark as acontract professor. His current research activ-ity is focused on the chemistry of heteroarenesincluding their sugar derivatives. He has pub-lished around 35 papers.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 23–74
74 Functions Containing Halogens and Any Other Elements
6.03
Functions Containing Three
Chalcogens (and No Halogens)
S. RADL
Research Institute of Pharmacy and Biochemistry, Prague,
Czech Republic
and
S. VOLTROVA
Institute of Chemical Technology, Prague, Czech Republic
6.03.1 INTRODUCTION 756.03.2 FUNCTIONS BEARING THREE OXYGEN ATOMS 766.03.2.1 Methods for the Preparation of Carboxylic Ortho-esters and Related Compounds 766.03.2.1.1 Ortho-esters from 1,1,1-trihaloalkanes, �,�-dihaloethers and �-haloacetals 766.03.2.1.2 Ortho-esters from imidate ester salts 776.03.2.1.3 Ortho-esters from carboxylic acids and derivatives 776.03.2.1.4 Ortho-esters from dioxacarbenium salts 806.03.2.1.5 Ortho-esters from 1,1-dialkoxyalkenes 816.03.2.1.6 Ortho-esters from 1,1-dialkoxycyclopropanes and related compounds 816.03.2.1.7 Ortho-esters from acetals 816.03.2.1.8 Ortho-esters from ortho-carbonate esters and trialkoxyacetonitriles 81
6.03.2.2 Preparation of Carboxylic Ortho-esters from Other Ortho-esters 826.03.2.2.1 Trans-esterification reactions 826.03.2.2.2 Modification of R1 and R2 of R1C (OR2)3 83
6.03.3 FUNCTIONS BEARING THREE SULFUR ATOMS 846.03.3.1 Methods for the Preparation of Trithio-ortho-esters and Related Compounds 846.03.3.1.1 Trithio-ortho-esters from RC(X1)(X2)X3 846.03.3.1.2 Trithio-ortho-esters from thioimidate esters salts 856.03.3.1.3 Trithio-ortho-esters from carboxylic acids and derivatives 856.03.3.1.4 Trithio-ortho-esters from dithia- and trithiacarbenium salts 856.03.3.1.5 Trithio-ortho-esters from dithioacetals 856.03.3.1.6 Trithio-ortho-formates from trithiocarbonates 866.03.3.1.7 Trithio-ortho-formates from tetrathio-ortho-carbonates 886.03.3.1.8 Miscellaneous 88
6.03.3.2 Preparation of Trithio-ortho-esters from Other Trithio-ortho-esters 896.03.3.2.1 Higher trithio-ortho-esters from trithio-ortho-formate esters 896.03.3.2.2 Trans-esterification of trithio-ortho-esters 93
6.03.3.3 Methods for the Preparation of Oxidized Derivatives of Trithio-ortho-esters 946.03.3.3.1 Oxidized trithio-ortho-esters containing at least one sulfoxide group 946.03.3.3.2 Oxidized trithio-ortho-esters containing at least one sulfone group 956.03.3.3.3 Oxidized trithio-ortho-esters containing at least one sulfonate group 97
6.03.4 FUNCTIONS BEARING THREE SELENIUM ATOMS 986.03.4.1 Methods for the Preparation of Triseleno-ortho-esters 986.03.4.1.1 Triseleno-ortho-esters from triselenacarbenium salts 986.03.4.1.2 Triseleno-ortho-esters from diselenoacetals and related compounds 98
75
6.03.5 MIXED CHALCOGEN FUNCTIONS INCLUDING OXYGEN 986.03.5.1 Methods for the Preparation of Functions R1C(OR2) (OR3)SR4 986.03.5.1.1 From R1C(X1)(X2)X3 986.03.5.1.2 Miscellaneous 100
6.03.5.2 Methods for the Preparation of Functions R1C(OR2) (SR3)SR4 1006.03.5.2.1 From R1C(X1)(X2)X3 1006.03.5.2.2 From dithiacarbenium salts 1016.03.5.2.3 From dithioacetals and related compounds 1016.03.5.2.4 From ketene dithioacetals 1016.03.5.2.5 Miscellaneous 105
6.03.5.3 Methods for the Preparation of Functions R1C (OR2) (OR3)SeR4 1056.03.6 MIXED SULFUR AND SELENIUM FUNCTIONS 1056.03.6.1 Methods for the Preparation of Functions R1C(SR2) (SR3)SeR4 1056.03.6.1.1 From dithioacetals 105
6.03.6.2 Methods for the Preparation of Functions R1C(SR2) (SeR3)SeR4 1066.03.7 MIXED OXYGEN, SULFUR, AND SELENIUM FUNCTIONS 106
6.03.1 INTRODUCTION
As in COFGT (1995) <1995COFGT(6)67>, this chapter covers synthesis of compounds ofgeneral formula R�C(X)(Y)Z where each of X, Y, and Z are independently linked through O,S, Se, and Te atoms. No compound of this type containing Te atoms has been reported in theliterature, so only compounds containing O, S, and Se are discussed. In some cases older principalarticles omitted in the basic work are included. Since 1993, no general review focused onpreparation of the structural types covered by this chapter has appeared.
6.03.2 FUNCTIONS BEARING THREE OXYGEN ATOMS
6.03.2.1 Methods for the Preparation of Carboxylic Ortho-esters and Related Compounds
6.03.2.1.1 Ortho-esters from 1,1,1-trihaloalkanes, a,a-dihaloethers and a-haloacetals
The extended Williamson synthesis of ortho-esters by nucleophilic displacement of three halogenatoms in 1,1,1-trihaloalkanes by sodium alkoxides has been used rarely owing to low yields<1995COFGT(6)67>. However, 3-chloro-2-trimethoxymethyl- or triethoxymethylpyrrole derivatives(2, R=Me, Et) have been prepared <1999T4133> from 3,3-dichloro-2-trichloromethyl-1-pyrroline 1and 10 equiv. of the corresponding sodium alkoxide in 97% and 79% yields, respectively (Equation (1)).
N
ClCl
Cl
ClCl
NaORHN
Cl
OR
OROR
1
79–97% R = Me, Et
2
ð1Þ
Nucleophilic displacement of the halogen atoms of �,�-dihaloethers (e.g., 2,2-dichloro-2-methoxyacetate <1995TL1827>) also gives ortho-esters. Thus, L-dimethyl tartrate was treatedwith phenylmagnesium bromide to give optically active tetraol 3, which reacted with the abovementioned dihaloether to afford the ortho-ester 4 used as a chiral auxiliary in the synthesis of�-hydroxy acids (Equation (2)).
PhPh
HO
Ph
Ph
OHOH
OHPh
PhHO
Ph
Ph
O
O
OMeO2C
+CO2Me
MeOCl
Cl
3
Py
90%
4
ð2Þ
76 Functions Containing Three Chalcogens (and No Halogens)
Reaction of bromomalonaldehyde tetraethylacetal 5 <1995T8623> with potassium t-butoxideafforded triethyl 3,3-diethoxy-ortho-propionate 6 via elimination of hydrogen bromide to diethoxy-methylketene diethylacetal (Scheme 1), cf. Section 6.03.2.1.5
6.03.2.1.2 Ortho-esters from imidate ester salts
Owing to the limited use of the Pinner method <1995T8623>, iminium salts were prepared fromsecondary or tertiary amides 7 <1997TL8499> by reaction with trifluoromethanesulfonic anhy-dride in the presence of pyridine at low temperatures. The resulting imino and iminium triflatesafforded ortho-esters 8 by reaction with alcohols (Scheme 2, R1=e.g., Ph(CH2)2, R
2 and R3=Hor alkyl, R4=alkyl). The yields of bridged ortho-ester 9 formed by reaction of suitable amideswith 2,2-bis(hydroxymethyl)-propan-1-ol were 59–88%.
O
OO
Ph9
Sugar 1,2-cyclic ortho-esters 12 can be prepared <2000CAR(329)879> from the correspondingperacetylated trichloroacetimidate 10 and t-butyldimethylsilylated alcohol 11 under the actionof usual promoters for trichloroacetimidate donors (0.1 equiv.): TMDMSOTf, BF3�Et2O, TfOH,AgOTf, in dry dichloromethane using 4 A molecular sieves (Scheme 3).
6.03.2.1.3 Ortho-esters from carboxylic acids and derivatives
Bicyclic ortho-esters reviewed in COFGT (1995) <1995COFGT(6)67> have been repeatedly usedas suitable protecting groups for polyfunctionalized carboxylic acids. A new method of utilizingortho-esters 15 both for protection and asymmetric synthesis has been developed <1997PAC639,
EtO OEt
OEt
Br
OEt
EtO OEt
OEt OEt
EtO OEt
OEt OEtt-BuOK EtOH OEt
5 6
Scheme 1
R1 NR2
O
R3R1 N
R2OTf
R3R1 N
R2OR4
R3
R4OH
R1
OR4
OR4OR4Tf2O, Py R4OH
7
+ +
8
Scheme 2
+O
AcO
AcO
OAc
AcO O
NH
CCl3
10
OTBDMSO
HO O
OOPh
11
OTBDMSO
O O
OOPh
OOO
AcOAcO
AcO
12
89%
Scheme 3
Functions Containing Three Chalcogens (and No Halogens) 77
1997T16575, 2003CC776>. The compounds can be prepared from oxiranes 13 using zirconoceneand AgClO4 in CH2Cl2 at mild conditions (room temperature, 15min). Mechanistically, thisortho-ester formation proceeds via dioxacarbenium ion intermediate 14 (Scheme 4).
Ortho-pivalates, as sugar protecting groups were prepared by reaction of pivaloyl chloride and freesugar using an HF-supported procedure <1994LA965, 1999JPR41> or by intramolecular ortho-esterification using dicyclohexylcarbodiimide (DCC) <1996MM6126, 2002CAR(337)951> or thioureain pyridine <1998CAR(308)439>. The last procedure is exemplified in Scheme 5 by preparation of18 from 16. During these procedures, dioxacarbenium ion intermediates, e.g., 17, are formed.
Similar conversion of a series of peracetylated sugars into the corresponding 1,2-ortho-esters viain situ generation of glycosyl iodides promoted by I2/Et3SiH followed by addition of the respec-tive alcohol has also been reported <2003TL7863>. Formation of oleanolyl 1,2-O-ortho-acetatesinstead of expected glycosides was studied under the conditions of Konigs–Knorr glycosidation<2001M839>. Thus, acetobromo sugars with diphenylmethyl-oleanolate in the presence ofdrierite, Ag2O, and iodine in dry chloroform afforded ortho-esters 19, where R=OAc, peracety-lated �- or �-D-glucopyranosyl, or �-D-galactopyranosyl, in ca. 30% yields.
O
R
OAc
OO
OAc
O
H
H
HO
PhO
Ph
19
Oxidative cyclization–methoxycarbonylation of propargylic acetates 20 in the presence of(CH3CN)2PdCl2/p-benzoquinone <2002TL6587> in methanol at 0 �C under CO atmos-phere afforded (E)-cyclic ortho-esters 21 in moderate yields (Equation (3), R1=Me, R2=Bn,or R1R2= (CH2CH2)2N-BOC).
OH
O
OR
OR
Cl
RO80 °C, 6 h
OH
O
RO
OR
O O
NH2CSNH2
16 17 18
MCA = ClCH2COR = Me3CCO
MCA
OH
O
RO
RO O O 66 %
MCA
+
Scheme 5
R O
O
O Cp2(Cl)Zr-Cl
AgClO4R O
O
OZr+(Cl)Cp2
O
ORZr(Cl)Cp2O
O
ORO
C(2)-attack
–Cp2(Cl)Zr++
13
1415
Scheme 4
78 Functions Containing Three Chalcogens (and No Halogens)
R1R2
AcOO
O
O
R1
R2O
O
20 21
i
i. (MeCN)2PdCl2/p-benzoquinone, MeOH, CO, 0 °C
ð3Þ
The mechanism proposed for this reaction includes formation of a vinyl palladium inter-mediate, which is subjected to nucleophilic attack of MeOH on the carbon atom of the acetylgroup followed by CO insertion and methanolysis to provide the ortho-ester product 21(Scheme 6).
Bis(trifluoroacetates) 22 react with bis(epoxides) 23 under the conditions of cycloaddition poly-merization to form poly(cyclic ortho-esters) 24 (Equation (4), R1=�(CH2)4�,�CH2C6H4CH2�,R2=�(CH2)2�, �C6H4�C(CH3)2�C6H4�). The yields are generally between 75% and 96%depending on the catalysts (onium salts, e.g., TBABr, TBACl, TBAI, tetrabutylphosphonium bro-mide) or solvents (N-methyl-2-pyrrolidone (NMP), anisole, chlorobenzene, tetrahydrofuran (THF),sulfolane) used <1995MM3490>.
F3C OR1
O CF3
O O+ O
R2
OO O
O
O OR1 O
CF3 O
O
F3C
OR2
O
n
22 23
24
ð4Þ
Spiro-ortho-esters (SOE) of general formula 25, easily accessible from lactones by reactionwith epibromohydrin (R=CH2Br) and further derivatization, undergo cationic polymer-ization. While at high temperatures (>100 �C) a double ring-opening process to givepoly(ether esters) 26 takes place, at low temperatures (<40 �C) single ring opening of theether ring to give poly(cyclic ortho-esters) (27) occurs (Scheme 7) <1994MM2380,1997MI241, 1999JPS(A)2551>. This polymerization is reversible and the obtained polymerscan be readily converted into the original monomers by treatment with acid catalysts atambient temperature.
R1R2
AcO
O
O
MeO
R1
R2
20
21
R1R2
O
O
Pd2+
O
OR2R1
MeOH
CO
O
O R2R1
COPd+
HO
MeOH
CO2MePd(0)
Pd2+
Benzoquinone
Hydroquinone
Pd+
H
+
Scheme 6
Functions Containing Three Chalcogens (and No Halogens) 79
6.03.2.1.4 Ortho-esters from dioxacarbenium salts
Preparation of ortho-esters from carboxylic acid derivatives often proceeds via dioxacarbeniumcation intermediates (cf. Section 6.03.2.1.3). The literature concerning dioxacarbenium tetrafluoro-borates was duly reviewed in COFGT (1995) <1995COFGT(6)67>. Transformations requiringphotoinduced electron transfer process involving dioxacarbenium ions will be discussed here.
Electron transfer from acetonides, e.g., 2,2-dimethyl-1,3-dioxolane 28, to the singlet excitedstate of benzene 1,2,4,5-tetracarbonitrile followed by fragmentation of the donor radical cationgave methyl radical and dioxacarbenium cation 29 <1992JOC3051, 2001T555>, which by hydro-lysis formed 2-hydroxyethyl acetate 31 via unstable ortho-acid 30. Methanolysis of 29 led to theformation of ortho-ester 32 (Scheme 8). This method was also applied for polyols and sugars<2001T555>.
Compound 33, available in high yields from ninhydrin, was irradiated with fumarodinitrile in benzenefor 5 h at 20 �C to give racemic 6:7-benzo-anellated 4-oxaspiro[2.5]octane-trans-1,2-dicarbonitrile 34in 32% yield <2002EJO2385>. The SOE 34 is the result of a cycloaddition of the dienophile witha dioxacarbenium ion intermediate (Equation (5)).
CN
NCO
OO
OO
33
O
O O
OOCN
CN
34
+
hνBenzene
32% ð5Þ
OO
Riii. >100 °C
iii. <40 °C
25
O
m
n
OO
R
On
m
26
27
O O
i, ii
O O
O Rn n
i. Epibromohydrin; ii. derivatization; iii. cationic catalyst
Scheme 7
O
O NC
NC
CN
CN
+
MeCNhν
CN–O
O+
NC
CN
CN
H2OMeOH
O
O
OH O
O
O
OOH
O
28 29
3031 32
+
Scheme 8
80 Functions Containing Three Chalcogens (and No Halogens)
6.03.2.1.5 Ortho-esters from 1,1-dialkoxyalkenes
Reaction of ketene dimethylacetal 36 with mono- and disaccharides led to cyclic ortho-esters atnonanomeric positions <1995CAR(267)227, 1998CAR(305)17>. For example 35 was trans-formed in 92% yield into 37 (Equation (6)). This sugar-protecting group can be selectivelyhydrolyzed under mild conditions.
+O
HO
OH
OH
OHOMe
35
CH2=C(OMe)2
36
OO
O
OH
OHOMe
MeO
37
92%
PTSA, DMFð6Þ
Substituted 2-alkoxyfurans 38 undergo dye-sensitized photo-oxygenation at low temperature(�80 to�70 �C)<1998SL17> to give 1-alkoxy-2,3,7-trioxabicyclo[2.2.1]hept-5-enes 39 (Equation (7)).
O
R3 R2
R4OR1
O OOR4
OR1
R3 R2
38 39
hν , –70 °C
ð7Þ
6.03.2.1.6 Ortho-esters from 1,1-dialkoxycyclopropanes and related compounds
This method of ortho-esters preparation was completely reviewed in chapter 6.03 of COFGT(1995) <1995COFGT(6)67> and no substantial progress has been made since.
6.03.2.1.7 Ortho-esters from acetals
Reactive 2-phenylseleno acetals 40 (R1=Bz, R2=Ph or polystyrene), obtained from sugarglycosides by 1,2-selenium migration, can be transformed to ortho-esters 41 (path A comprisingoxidative cleavage and ring closure, R3=protecting group) and allyl ortho-esters 42 (path Bincluding oxidative cleavage, ring closure, and Ferrier-type rearrangement, R3=H) (Scheme 9)<2000AG(E)1089, 2000MI3149, 2000MI3166>.
6.03.2.1.8 Ortho-esters from ortho-carbonate esters and trialkoxyacetonitriles
This method of ortho-esters preparation was completely reviewed in COFGT (1995)<1995COFGT(6)67> and no substantial progress has been reported since.
O
OR3
O
SeR2
OR1
O
R3OO
O O
R3OO
O
A B
40
41 42
Scheme 9
Functions Containing Three Chalcogens (and No Halogens) 81
6.03.2.2 Preparation of Carboxylic Ortho-esters from Other Ortho-esters
6.03.2.2.1 Trans-esterification reactions
Trans-ortho-esterification reactions with simple alcohols was duly reviewed in COFGT(1995) <1995COFGT(6)67> and only few improved methods have appeared since 1993.A series of chiral ortho-esters was prepared by re-esterification of triethyl ortho-acrylatewith chiral substituted 1,2-diols in CH2Cl2 catalyzed by MgCl2 <1997TA139>. Similarly, 4,6-O-(1-ethoxy-2-propenylidene)sucrose 43 was prepared from sucrose in anhydrous dimethlyformamide(DMF) in the presence of pyridinium p-toluenesulfonate (PPTS) at ambient temperaturefollowed by acetylation of the crude reaction mixture <1993CAR(240)143>. 2-Ethoxymethyl- or2-(2-methoxyethyl) propane-1,3-diol was heated with triethyl ortho-formate, -acetate, or -benzoateat 150 �C to give 1,3-dioxane derivatives 44 <1994CJC2084>.
O
O
R1
R2
OEt
OO
AcO
OAcO
OAc
AcOO
AcO
O
OEt
OAc
4443
R1 = EtOCH2, MeOCH2CH2
R2 = H, Me, Ph
Equilibrium polymerization reaction, as was shown in Section 6.03.2.1.3, can be alsoregarded as a trans-ortho-esterification reaction <1994MM2380, 1997MI241, 1999JPS(A)2551>.A further example of polymerization re-esterification is the reaction of 8-substituted 1,6,10-triox-aspiro[4.5]decane 45 in the presence of boron trifluoride diethyl etherate to give poly(cyclic ortho-ester) 46 as the intermediate (Scheme 10) during polymerization to the corresponding poly(etheresters) <1998JPS(A)2439>.
Certain progress from 1993 is obvious in the chemistry of bicyclic ortho-esters of generalformula 47 (e.g., OBO=2,6,7-trioxabicyclo[2.2.2]octan-1-yl derivatives 47, R2=H) and tricyclicortho-esters 48, which are often used as alcohol or carboxyl protecting groups.
O O
O
R1
R2
OO
O
R1
47 48
O
O OR
O
OR
BF3 .Et 2O
O
O OR
O O
R
45
46
+O–
O
O
OR+–O
O O
R
OOO
R
O
n
Scheme 10
82 Functions Containing Three Chalcogens (and No Halogens)
Trans-ortho-esterification reactions of glycerol, 2-hydroxymethyl-2-methylpropane-1,3-diol, or2,2-bis(hydroxymethyl)propane-1,3-diol with triethyl ortho-formate, -acetate, and -propionatewere carried out at 100–140 �C in the presence of an acid catalyst to obtain OBO derivatives<2002MI225>. The best result, a yield of about 90%, was obtained in the reaction of penta-erythritol with triethyl ortho-propionate in diglyme.
The bulky OBO ester function has been shown to be a useful protecting group of amino acidse.g., aspartic or glutamic acid, for preventing epimerization at the �-carbon and to induce gooddiastereoselectivities, e.g., in diazomethane cycloadditions <1999JOC8958, 2003MI36>.
1,2,5-Ortho-esters of D-arabinose <2002EJO3864> and a 1,2,6-ortho-ester of mannose<1999TL6423> have been described and their use in the glycosylation reaction has been studied.Tricyclic ortho-esters have been used for regioselective protection of polyalcohols <2000TL4185,2002CAR(337)2399>. Thus, 4,6-di-O-benzyl-myo-inositol 50 was conveniently prepared via1,3,5-ortho-ester 49, obtained by transesterification from ortho-formates or -acetates<2001CAR(330)409, 2002MI63> (Scheme 11).
6.03.2.2.2 Modification of R1 and R2 of R1C (OR2)3
This method of ortho-ester preparation was completely reviewed in COFGT (1995)<1995COFGT(6)67>. 1,1,1-Triethoxypropyne 51 was prepared in 77% yield from trimethylsilyl-acetylene and triethoxycarbenium tetrafluoroborate in two steps <1997TL6803> (Scheme 12).
As one example of the R2 modification, the radical addition of dithiols (R=�(CH2)3�,�(CH2)6�, or�CH2�C6H4�CH2�) to polymer 52, carried out at 20 �C in the presence of2,20-azobisisobutyronitrile (AIBN) under ultraviolet (UV) irradiation in benzene for 4 h, affordsthe corresponding crosslinked poly(cyclic ortho-esters), which could be depolymerized to bifunc-tional monomers 53 (Scheme 13) <1997MI241>.
HO
HOOH
HO
OHOH
i. DMF, RC(OEt)3ii. Py, BzCl
BzOO
OH
O O
BzO
i. DMF, Ag2O, BnBrii. MeOH, i-BuNH2
HOO
OBn
O O
BnO
TFA, H2O
HO
HOOBn
HO
OHOBn
50
49
R
R
R = H, Me
Scheme 11
51
TMS
i. BuLiii. H2O
TMSOEt
OEtOEt
i. BuLi
ii. (EtO)3C+BF4– OEt
OEtOEt
Scheme 12
Functions Containing Three Chalcogens (and No Halogens) 83
6.03.3 FUNCTIONS BEARING THREE SULFUR ATOMS
6.03.3.1 Methods for the Preparation of Trithio-ortho-esters and Related Compounds
6.03.3.1.1 Trithio-ortho-esters from RC(X1)(X2)X3
(i) From 1,1,1-trihaloalkanes
This methodology using trihaloalkanes (X1=X2=X3=halogen) was duly covered in COFGT(1995) <1995COFGT(6)67>. The reaction has been frequently used for preparation of both trialkyland triaryl trithio-ortho-formates. Usually the reaction is done in the presence of a strong base.However, in the case of polyfluorothiophenol, extensive polymerization was observed under basicconditions. The reaction of pentafluorothiophenol 54with iodoform in DMF was performed withoutany base providing tris(pentafluorophenylsulfanyl)methane 55, besides some polymeric products<1971TL2475>. Attempts to improve the reaction of 54 with chloroform and tetrachloromethaneby the presence of AlCl3 ledmainly to diarylated products 56, together with 57. Only small amounts ofthe expected triarylated compound 55 were formed <1999JFC(98)17> (Scheme 14).
(ii) From �-halodithioacetals and �,�-dihalothioethers
�-Chlorodithioacetal 58 treated with methanethiol provided the corresponding product 59<1997AJC683> (Equation (8)).
MeS S SMe
O O
Cl
MeSH MeS S SMe
O O
SMe
58 59
ð8Þ
SH
FF
F
F F
54
S
FF
F
F F
CH
S
FF
F
F F
CXCl S
FF
F
F F
CHI3, DMF
3
X-CCl3, AlCl3X = H, Cl
2
+ + 55
2
55
56 57
Scheme 14
O O
HS-R-SHAIBN, hν TFA, CH2Cl2
52
53
O
2n
5
O O
O
n
5
SR
S
O O
On5
O
OS
RS
O
O
O
O
Scheme 13
84 Functions Containing Three Chalcogens (and No Halogens)
Similarly, alkylation of thiophenol with chloro derivative 61 generated in situ from 1,3-dithiane60 gave 44% yield of 62 <1994SL547> (Scheme 15).
Easily obtained dibromo derivative 63 treated with ethanethiol in the presence of silver triflategave 91% yield of 64 <1996CAR(282)237> (Equation (9)).
EtSH, TfOAgS
AcO OAcOAc
Br
BrS
AcO OAcOAc
SEt
SEt
63 64
91% ð9Þ
6.03.3.1.2 Trithio-ortho-esters from thioimidate esters salts
This part covering reactions shown in Equation (10) was duly reviewed in chapter 6.03 in COFGT(1995) <1995COFGT(6)67> and no substantial progress has been achieved since.
R1SR2
NH2+X–
R3SHR1
SR3
SR3SR3 ð10Þ
6.03.3.1.3 Trithio-ortho-esters from carboxylic acids and derivatives
As summarized in COFGT (1995) <1995COFGT(6)67>, acyl chlorides bearing no �-hydrogenatom with thiols in the presence of suitable catalysts, e.g., ZnCl2 or AlCl3, provide acceptableyields of the corresponding trithio-ortho-esters. The method was used with various chlorides ofaromatic carboxylic acids <1986TL4861, 1997JOC2917>.
6.03.3.1.4 Trithio-ortho-esters from dithia- and trithiacarbenium salts
Addition of thiols or other suitable sulfur nucleophiles to dithia- and trithiacarbenium salts wasreviewed in COFGT (1995)<1995COFGT(6)67>. Regarding the reaction with dithiocarbenium salts,no progress has been made since. Trithiocarbenium salts are often generated from the correspondingtrithiocarbonates and their reactions and progress in this field is covered in Section 6.03.3.1.6.
6.03.3.1.5 Trithio-ortho-esters from dithioacetals
The most common procedure converts dithioacetals by deprotonation with a strong base to ametallated intermediate, which upon treatment with a disulfide provides the final trithio-ortho-esters. The procedure was summarized in COFGT (1995) <1995COFGT(6)67>. Similar conditionswere also used for the preparation of tris(trifluoromethylsulfanyl)methyl cyanide 66 from 65 usingeither the corresponding sulfenyl chloride or disulfide <1994CB449> (Equation (11)).
CNF3CS
F3CS SCF3
F3CS
F3CSCN
i. NaHii. CF3SCl or (CF3S–)2
6665
ð11Þ
S SS S
Cl
PhSH S S
SPh44 %
NCS
60 61 62
Scheme 15
Functions Containing Three Chalcogens (and No Halogens) 85
Trimethylsilyl tetrathiophosphate 67 treated with dithioacetal 68 gave 69 <1994ZOB1333>(Equation (12)).
PS
S SiMe3EtS SEt
+ H2C(SEt)2 PS
SEtS SEt SEt
SEt
67 68 69
ð12Þ
6.03.3.1.6 Trithio-ortho-formates from trithiocarbonates
As reviewed in <1995COFGT(6)67>, trithiocarbonates treated with alkyllithiums at �78 �Cfollowed by quenching with an acid provided the corresponding trithio-ortho-formates. Themethodology was later extended to the six-membered 1,3-dithiane 70 and compound 71 wasprepared by this method (Scheme 16). When the intermediate anion was treated with analkylating agent before the quenching, high yields (75–89%) of substituted analogs 72 wereobtained. When the mixture was allowed to reach ambient temperature before the quenching,the corresponding thioacetals 73 and 74 were formed <1991CL1315>.
Compound 75, prepared by the above-mentioned method, was deprotonated with methyl-lithium and the formed anion 76 was treated with dithione 77 and then with an excessof iodomethane to give an acceptable yield of complex structure 78 <1996SM175> (Scheme 17).
Fluorine ion-induced reaction of allyl and benzyl silanes with both linear and cyclic trithiocar-bonates provided good yields of the corresponding trithio-ortho-esters <1994TL161> (Equations(13) and (14)).
S
SS
i. BuLi, –78 °Cii. H+
S
SSBu
i. BuLi, rt
ii. H+
S
SBu i. BuLi, –78 °C
ii. RX
iii. H+
S
S SBu
R
i. BuLi, rt
ii. RX, 0 °C
iii. H+
S
S Bu
R R = Me, Et, Pr, i-Pr, Bu
70 71
72
73
74
Scheme 16
OMe
OMe
S
SS
SS Si.
ii. MeI
55%
S
SSMe
BuS
BuS75
77
OMe
OMe
S
SS
S S
S
S
S SBuBuS
BuS
SMe
MeS
SMe
MeS SBu
78
S
SSMe
BuS
BuS
–
76
Li+
Scheme 17
86 Functions Containing Three Chalcogens (and No Halogens)
SPhPhS
S PhTBAF
67% PhS SPh
S+ Ph SiMe3 ð13Þ
TBAF
71% S S
SSiMe3
S S
S
+ ð14Þ
Readily available oxazolidinone derivative 79, as an equivalent of stabilized oxomethine ylide80, reacted with trithiocarbonate 81 as dipolarophile giving cycloadduct 82 as a racemate andonly the shown regioisomer was detected (Scheme 18). Derivatives of 79 bearing at C-6 t-butyl-dimethylsilyl (TBDMS)-protected (R)-�-hydroxyethyl substituent gave the correspondingcycloadduct in only 20% yield <1997JOC3438>.
One of the methods frequently used for the synthesis of 2-alkylsulfanyl-1,3-dithiole derivatives85 is shown in Scheme 19. The method is based on reduction of alkylsulfanyl-1,3-dithiolium salts84, easily obtained from the corresponding 1,3-dithiole-2-thiones 83 <1994JOC5324,1994JOC6519, 1996JCS(P1)783, 1996SM175, 1997JOC1903, 1997S26, 1998CC361, 1998JMAC1185,2001EJO933, 2001MI145, 2001SM97, 2002JMAC2137>.
Alkylation of 83 is done with common alkylation agents, e.g., iodomethane <1994JOC6519>,dialkyl sulfate followed by tetrafluoroboric acid <1996JCS(P1)783, 1997S26, 2001MI145>, methyltriflate <1994JOC5324, 1997JOC1903, 1998CC361, 1998JMAC1185, 2001EJO933, 2001SM97,2002JMAC2137>, or dimethoxycarbenium tetrafluoroborate formed in situ from ortho-formateand boron trifluoride diethyl etherate <1996SM175>. Yields of the corresponding dithiolium saltsare frequently nearly quantitative. The reduction step is usually done with sodium borohydride andyields are also usually high, very often over 90%. Only very rarely did the borohydride reductionlead to decomposition and use of sodium cyanoborohydride was necessary <1994JOC5324,2001EJO933>. Compounds 85 are of a great interest since they are intermediates of fulvanederivatives studied as perspective synthetic materials. Besides the mentioned references, there aremany others using the same procedure without isolating the 2-alkylsulfanyl-1,3-dithiole intermedi-ates. Some interesting structures, for example crown ether derivative 86 <2001EJO933> and[60]fullerene derivative 87 <2002JMAC2137> have been synthesized by this method.
S
SSMe
S
S
OO
OO
S
SSMe
86 87
MeCN
80 °CN
OH
O
O
CO2PNB
79
N+O
CO2PNB–
80
MeS SMe
S
60%
81N
SH
OCO2PNB
SMe
SMe
82
Scheme 18
R3X
S
SS
R1
R2
83
S
SSR3
R1
R2
+X–
84
S
SSR3
R1
R2
85
Scheme 19
Functions Containing Three Chalcogens (and No Halogens) 87
Dithiolium salts, e.g., 88, can be reduced with zinc to give the corresponding dimeric products,e.g., 89 <1990KGS471> (Equation (15)).
S
SSEt+
S
SZn
S
SSEt
EtS
S
X
S
S
X
S S
X
S
X = CO, O, S88 89
X–
ð15Þ
The triflate salt of 84 reacted with anions generated in situ from anthrone <1999OL2005> orcyclononatetraene <1994HCA1377> with lithium diisopropylcyclohexylamide (LDA) to givecompounds 90 and 91, respectively.
SS
SMe
91
O
SS
SMe
R2R1
90
6.03.3.1.7 Trithio-ortho-formates from tetrathio-ortho-carbonates
Seebach has reported transformation of tetrathio-ortho-carbonate to trithio-ortho-formate bytreatment with BuLi at low temperature followed by quenching with water <1967AG(E)443>and the method has been used several times since <1995COFGT(6)67>.
Arsenic pentafluoride oxidized (F3CS)4C to the stable salt (F3CS)3C+AsF�6 92, which treated
with halide ions provided good-to-excellent yields of the corresponding trithio-ortho-esters 93.Under the described reaction conditions using potassium iodide, the oxidation product 94 wasobtained in 86% yield <1994CB597> (Scheme 20).
6.03.3.1.8 Miscellaneous
2-Methoxy-1,3-dithiolane 95 with silylated thymine did not provide the expected 1,3-dithiolan-2-yl nucleoside but 1,2-bis(1,3-dithiolan-2-yl)dithioethane 96 was obtained in 92% yield instead<1996JOC3611> (Equation (16)). This compound can also be obtained from trialkyl ortho-formates and ethanedithiol <1972HCA75>.
SO2
X–
X = F, Cl, Br
SCF3
SCF3
SCF3F3CS
F3CSF3CS
KI
86 %
XF3CS
F3CSF3CS
92
93 94
2 (F3CS)4C + 3AsF5 2 (F3CS)4C+ AsF6 + AsF3 + F3CS-SCF3–
Scheme 20
88 Functions Containing Three Chalcogens (and No Halogens)
S
SOMe S
SS
SS
S
95 96
92% 23 ð16Þ
Addition of thiols to quinone methides 97 provided the corresponding trithio-ortho-esters 98in yields between 44% and 99% <1995PS(107)119> (Equation (17)).
OMeMe
SR2R1S
R3SH
OHMeMe
SR2R1SSR3
97 98
ð17Þ
6.03.3.2 Preparation of Trithio-ortho-esters from Other Trithio-ortho-esters
6.03.3.2.1 Higher trithio-ortho-esters from trithio-ortho-formate esters
Transformation of trithio-ortho-esters, mainly via the corresponding lithium salts, has becomeone of the most important methods of preparation of higher trithio-ortho-esters. The lithiumsalts are usually generated by BuLi at �78 �C as described by Seebach <1967AG(E)443,1969S17, 1972CB487, 1972CB3280>. Selected examples of utilization of such lithium salts aregiven below.
(i) Alkylation with alkyl halides or triflates
Alkylation of LiC(SMe)3 with a wide range of alkyl halides provided good yields of the corre-sponding trithio-ortho-esters, which were used as intermediates of the synthesis of methyl thiol-carboxylates <1993JCS(P1)2075>. Alkylation of LiC(SMe)3 with 4-bromobutyric acid providedquantitative yield of 5-tris(methylsulfanyl)pentanoic acid <2000JOC235>. Similar alkylation with1-azido-3-iodopropane led to 91% yield of the corresponding azido derivative, which was used inthe synthesis of a reversed thioester analog of acetyl-coenzyme A <1998JA3275>. Nucleophilicdisplacement of allylic chloride 99 with LiC(SMe)3 at low temperature led to an excellent yield ofalkylated trithio-ortho-ester 100, which was utilized as a carboxyl anion equivalent to the synthesisof ester 101 <1994JOC4853> (Scheme 21).
Similarly, high yields of sartane analog 102 <1994TL9391> as well as pyran derivative 103<2002CEJ1670> were obtained by the reaction of suitable lithium salts with the correspondingiodo and triflate derivatives, respectively.
THP-O Cl
LiC(SMe)3
97% THP-O (SMe)3
THP-O COOMe
55 %
99 100
101
C
Scheme 21
Functions Containing Three Chalcogens (and No Halogens) 89
N
N
Cl
O-TBDMSBu
ArSMe
S SO SMe
SMeSMe
OO
102 103
(ii) Reaction with aldehydes and ketones
Tris(alkylsulfanyl)methyllithiums are known to react with a wide range of aldehydes from simpleones e.g., 3-hydroxy-2,2-dimethylpropionaldehyde <1999JOC2903>, 6-isopropyl-3-methylhept-6-en-1-al <1996JCS(P1)349>, pentadec-5-en-1-al <1998TL3115>, to much more complex alde-hydes derived from amino acids <1995BMC1063> or sugars <1999SC3841, 2000TL307>.Usually good-to-high yields of the respective hydroxy derivatives 104 are obtained. The formedhydroxy derivatives are either isolated, or in situ oxidized to the corresponding oxo derivatives105 <2001JOC5822>, or alkylated to their O-alkyl derivatives 106 <1998TL3115>. Hydroxytrithio-ortho-esters 104 are often transformed to various carboxylic acid derivatives e.g., 107 or108 (Scheme 22) in the following steps.
In spite of the report on the 1,2-addition of LiC(SMe)3 on acrolein <2001JOC5822>, a differentpaper reported that reaction of LiC(SPh)3 with acrolein gave the 1,2- and 1,4-adducts in a 3:5ratio <1995TL8925>.
In the case of chiral compounds, the stereoselectivity of this reaction varies <1995BMC1063,1996JOC6685, 1997JOC3880, 1999SC3841, 2000TL307> and only rarely is one stereoisomerobtained. This is the case when bulky LiC(SPh)3 reacted with protected aldehyde 109 whereL-ido derivative 110 was obtained as the only isomer in 92% yield <2000TL307> (Equation (18)).
OOBn
OO
CHO
OOBn
OO
OHC(SPh)3
92%
109 110
LiC(SPh)3
ð18Þ
+ (MeS)3CLiR C(SMe)3
R-CHOOH
R = CH2=CH-, HOCH2CMe2-, Me2CHC(=CH2)CH2CH2CHMeCH2-, Me(CH2)8CH=CH(CH2)3CHO
R C(SMe)3
O
R C(SMe)3
OMe
R COOMe
OH
R
OHSMe
O
104
105
106
107
108
Scheme 22
90 Functions Containing Three Chalcogens (and No Halogens)
In the case of ketone 111, the reaction is stereoselective even for LiC(SMe)3 giving 94% of theisomer 112 (Equation (19)). No 1,4-addition was observed <1996JOC6685>. High yield (78%)and similar stereoselectivity was also reported for the reaction of (S)-2-acetylpyrrolidine trifluoro-acetate with an excess of LiC(SMe)3 <1997JA6984>.
O
O O
O
O
O
O
OH
C(SMe)3
111 112
94%
OBn OBn
LiC(MeS)3
ð19Þ
(iii) Reaction with epoxides
Terminal epoxides generally react with LiC(SPh)3 to give only low yields of �-hydroxy trithio-ortho-formates <1967AG(E)443, 1972CB487>. However, a modification of this method usingLiC(SMe)3 is reported to give good-to-excellent yields of 113, which can be easily converted to�-hydroxyesters <1993SC811> (Equation (20)).
O
R
R = Me, PhO, PhCH2O
RC(SMe)3
OH
113
LiC(MeS)3
ð20Þ
(iv) Reaction with �,�-unsaturated ketones or esters
Addition of sulfur stabilized carbanions e.g., LiC(SPh)3, to unhindered �,�-unsaturated ketoneshas been reported to produce high yields of the 1,4-addition products <1975CC216, 1977TL3549,1990JOC1198, 1990JOC2132>. The ready availability of such adducts combined with the varietyof possible transformations of the trithio-ortho-ester unit make the reaction potentially useful. Thesame reaction with exocyclic derivative 114 provided only 24% yield of the product. However,when the reaction was done in the presence of trimethylsilyl chloride (TMSCl), the yield wassubstantially improved and 75% yield of 115 was obtained (Equation (21)). The same modifica-tion was found useful also with noncyclic compounds 116 and the corresponding ketones or esters117 were obtained in good yields <1995TL8925> (Equation (22)).
O
TMSCl, LiC(SPh)3
O
C(SPh)3
75%
114 115
ð21Þ
TMSCl, LiC(SPh)3
R
O
R
O
(PhS)3CR = Me, 96% R = OMe, 69%
116 117
ð22Þ
Cyclic �,�-unsaturated lactones add lithiated trithio-ortho-esters to the �,�-double bond togive the corresponding lithium salts 119. This reaction was described for several�-angelicalactone derivatives 118, the formed lithium salts can be either quenched with aqu-eous solutions to give the corresponding saturated compounds 120 <1995JOC5628,2003BMC357>, or further alkylated to 121 <1994TL4123, 1995JOC5628>, or transformedby reaction with tosyl azide to the corresponding azides 122 <1999JOC2657> (Scheme 23).Enantioselective synthesis of R-2-methyl-1,4-butanediol from 5R-(1-menthyloxy)-5-furan-2-onebased on the Michael addition of LiC(SPh)3 and the following Raney nickel desulfuration hasbeen reported <1992SC1367>.
Functions Containing Three Chalcogens (and No Halogens) 91
Nucleophilic addition of LiC(SMe)3 to carbaldehyde-derived 2,3-dihydro-4H-pyran-4-one 123yielded a mixture of both 1,2- and 1,4-addition products 124 and 125, respectively. Depending onthe conformation on the C-2 atom, either 1,2- or 1,4-adducts were preferentially formed<1997T7867> (Equation (23)).
+
O
OBnO
BnO
123
O
BnO
BnO
HO C(SMe)3
124
LiC(SMe)3
125
O
OBnO
BnOC(SMe)3
ð23Þ
Tricyclic xanthone derivative 126 added LiC(SMe)3 in a 1,4-manner to give 35% of product 127<1997JCS(P1)1819> (Equation (24)).
O
O O
O
O OH
C(SMe)3
35%
LiC(SMe)3
126 127
ð24Þ
Addition of LiC(SMe)3 to methyl acrylate gave 40% yield of methyl 4,4,4-tris(methylsulfanyl)-butyrate <2000JOC235>.
(v) Reaction with carboxylic derivatives
Tris(alkylsulfanyl)methyllithiums are known to react with both aliphatic <1995JOC6017> andaromatic <1995JOC6017, 1996JOC9572, 1996S467, 2001TL8189, 2002S921> carboxylic acidesters to provide 128. The reports showed that the reaction should be optimized to suppressformation of side products to provide good yields of the desired products. In particular, aromaticderivatives are versatile intermediates in the synthesis of aryl bis(alkylsulfanyl)thioacetates 129<1997JOC7228, 2002S921>, �-ketothioesters 130 <1996S467, 2001TL8189> or �-ketoacids 131<2001TL8189> (Scheme 24).
Similar reaction of LiC(SMe)3 with other carboxylic acid derivatives such as acyl chlorides,anhydrides, or thioesters leading to variable yields of identical products have also been described.The yields of the required products were substantially enhanced when N-(methylsulfanyl)phtha-limide was used in the work-up procedure <1996JOC9572>.
R = Me, Bu, TBDPS-O
O ORO OR
(PhS)3C Li
O OR
(PhS)3C
O OR
(PhS)3C
O OR
(PhS)3C N3
118 119
120
121
122
(PhS)3CLi
Scheme 23
92 Functions Containing Three Chalcogens (and No Halogens)
(vi) Miscellaneous
Azulene treated with LiC(SMe)3 gave intermediate 132, which was oxidized with chloranil toprovide practically quantitative yield of crude derivative 133 <2001S1346> (Scheme 25).
6.03.3.2.2 Trans-esterification of trithio-ortho-esters
No substantial achievements have been reported since COFGT (1995) <1995COFGT(6)67> waspublished.
(i) Modification of R1 and R2 of R1C (SR2)3
Bromine–lithium exchange of trithio-ortho-ester 134 was used to generate the correspondinglithium salt <1980JOC740>, which after the treatment with tris(perfluorodecylethyl)silyl bromidegave fluorous trithio-ortho-ester 135 <1997JOC2917> (Equation (25)).
Br
SPr
PrSSPr
i. BuLiii. (C10F21CH2CH2)3SiBr
(C10F21CH2CH2)3Si
SPr
PrSSPr
134 135
ð25Þ
Various substituent modifications were done with cyano derivative 66, which can be pre-pared either from 65 (Section 6.03.3.1.5) or by alkylation of silver cyanide with bromoderivative 136. Acidic hydrolysis of 66 with sulfuric acid provided nearly quantitatively thecorresponding amide 137. Its treatment with oxalyl chloride provided either 138 or 139,depending on the ratio of the reactants, while similar treatment with phosgene failed<1994CB449> (Scheme 26).
LiC(SR)3
Ar OMe
O
Ar C(SR)3
O
Ar
OSR
O
Ar COOH
O
Ar
RS SRSR
O
128
129
130
131
Scheme 24
LiC(SMe)3C(SMe)3
132
C(SMe)3
133
Chloranil
quant.
Scheme 25
Functions Containing Three Chalcogens (and No Halogens) 93
6.03.3.3 Methods for the Preparation of Oxidized Derivatives of Trithio-ortho-esters
6.03.3.3.1 Oxidized trithio-ortho-esters containing at least one sulfoxide group
Sulfoxide 140 treated with LDA and methyldisulfanylmethane provided 70% of 141 as the onlyisolated product <1998BMCL3331> (Equation (26)).
LDA, MeSSMe
70% H2NS
Me
OMOM-O
H2NSO
MOM-O
SMe
SMe
140 141
ð26Þ
Reaction of trithiocarbonates 142 with 3-chloroperoxybenzoic acid (MCPBA) afforded thecorresponding S-oxides 143, which reacted with organolithium compounds, e.g., methyllithium,at low temperatures in a thiophilic manner to give carbanions 144 stabilized by three sulfur atoms<1997T1323>. Hydrolysis afforded trithio-ortho-ester oxides 145 which are unstable at ambienttemperature. For unsymmetrical trithiocarbonates 142, a 1:1 mixture of both possible diastereoi-somers was obtained. Carbanions 144 can also be trapped by other electrophiles, e.g., iodo-methane in the presence of hexamethylphosphoramide (HMPA) provided 94% of 146. Additionof the anion to enones provided either unstable adducts 147 or directly their degradation products148 (Scheme 27).
Generation of the corresponding bridgehead carbanion from 149 followed by treatment withiodoalkanes provided no expected substituted trithiolanes and the reaction led to unexpectedproducts, the nature of which was strongly dependent on the electrophile added. When theanion was treated with iodomethane or iodoethane, compounds 150 were isolated and theirstructure was proved by X-ray crystallography. However, less reactive 2-bromopropane didnot react at �78 �C and at room temperature provided compound 151 <1999T10341>(Scheme 28).
H2SO4
97 %
AgCN
1 equiv. (COCl)20.5 equiv. (COCl)2
F3CSNH
NH
OO OSCF3
SCF3SCF3
SCF3F3CS
F3CSN
O
SCF3F3CS
C O
F3CSNH2
O
SCF3F3CS
F3CSCN
F3CSF3CS
F3CSBr
F3CSF3CS
60% 70%
136 66 137
139138
Scheme 26
MeLi
H2OMeI
R1S SR2
SOMe
R1S SR2
SOMeMe
R1S SR2Me
Me
O– R3SOH
Me
OMe
R1S
R2S
SO
Me
R1S SR2
S
142
R1S SR2
SO
143
R1S SR2
SOMe
–
144
145146147148
MCPBA
MeCH=CH-CHO
Scheme 27
94 Functions Containing Three Chalcogens (and No Halogens)
Silanes have also been successfully used as alternative nucleophiles for the thiophilic addition.S-Oxide 152 treated with allyl and benzyl trimethylsilane in the presence of tetrabutylammoniumfluoride provided 38–41% yields of the respective products 153 <1997T1323> (Equation (27)).
RSiMe3, TBAF
S S S S38–41%
SO
SR O
152 153
ð27Þ
Oxidation of triaryl trithio-ortho-esters with organic peroxy acids leading to triaryl sulfoxides iswell known. Asymmetric oxidation of 2-phenylsulfanyl-1,3-dithiane 154 using modified Sharplessconditions led to 65% yield of the corresponding anti-R-oxide 155 but the enantiomeric excess(ee) achieved was poor (Equation (28)). No exocyclic oxidation was observed either for com-pound 154 or for the similar methylsulfanyl derivative <1996T2125>.
65%
Ti(O-i Pr)4,DET, TBHP
S S
SPh
154
S S+
SPhO–
155
ð28Þ
6.03.3.3.2 Oxidized trithio-ortho-esters containing at least one sulfone group
Treatment of 2-lithium-1,3-dithiane 156 with tosyl azide gave no dimer 157 but instead low yieldof the corresponding 2-tosyl derivative 158 was obtained, together with major amounts ofunidentified products <1997T9269> (Scheme 29).
2,5-Norbornadiene 159a and 2,5-norbornene 159b were added in diffuse daylight C-sulfonyl-dithioformate 160 in a [2 +2] fashion to give 161a (92%) and 161b (80%), respectively (Equation(29)). The compounds in crystalline form are stable in the dark <1995SUL(19)29>. Similartreatment of 160 with hex-1-ene provided the corresponding ene-reaction product<1995SUL(19)59> 162. Thermal reaction of 160 with tetramethylallene provided more than90% yields of the corresponding ene-products (Equation (30)).
80–92%
hν+
159a,b
S
R1SSO2R2
161a,b
R1SR2
S
O O160
S ð29Þ
SSPh H
S
O i. LDA, THF, –78 °Cii. 2-PrBr, rt S O
PhSS
SPhS
OSR
i. LDA, THF, –78 °Cii. RI, –78 °C
79–90 %
149150 151
Scheme 28
17%
S
SLi
S
SS
S
STos
156157 158
TosN3S
Scheme 29
Functions Containing Three Chalcogens (and No Halogens) 95
+R1S S
R2S
O O
162
80% hν
R1SR2
S
O O
160
S ð30Þ
Sulfonyldithioformates 160 treated with dienes, e.g., cyclopentadiene or substituted buta-dienes, provided good yields of the corresponding adducts, e.g., 163 <1995SUL(18)215>(Equation (31)).
+ R1S SR2
S
O O
160
SR1S
R2O2S
163
ð31Þ
Allyldithiobenzoate 164 was oxidized by air oxygen to provide, beside the allyl thiobenzoate166, also 1-phenyl-2,6,7-trithiabicyclo[2.2.1]heptane-2,2-oxide 165 at a rate of 7% a month(Equation (32)). The structure was proved by X-ray diffraction but the total yield achieved wasnot given <1995SUL(18)67, 1995T11503>.
Ph S
S
Ph S
O+
S S
S
Ph OO
air O2
165 166164
ð32Þ
Bis(methanesulfonyl) (ethylsulfanyl)methane 168, also easily available from bis(methanesulfonyl)-methane, was prepared in 87% yield by treatment of 167 with sodium ethanethiolate. Compound168 treated with 2 equiv. of BuLi followed by iodopentane provided monoalkylation product 169and dialkylation product 170 in 76% and 17% yields, respectively <2002TL1377> (Scheme 30).
Though oxidation of hexathiaadamantane derivative 171 with 2 equiv. of MCPBA provided acomplex mixture of mono-, bis-, and tris-S-oxides, the same reaction with 25 equiv. of MCPBA orMnO2 led to regioselective formation of 172, which was obtained in 69% and 60% yields as theonly detectable product <2000JCS(P2)1777> (Equation (33)).
S SS
SSS
MnO2, 60% O2S SO2
SS
SO2O2S
171 172
MCPBA, 69% ð33Þ
EtSNa, NaH
87%
i. 2equiv. BuLiii. Me(CH2)4I
MeS S
MeEtS SEt
O O O O
167
MeS S
MeEtS H
O O O O
168
MeS S
(CH2)5MeEtS H
O O O O
Me(CH2)5S S
(CH2)5MeEtS H
O O O O
+
16976%
17017%
Scheme 30
96 Functions Containing Three Chalcogens (and No Halogens)
Sulfonylmethane derivative 173 treated with N-phenyltrifluoromethane sulfinimide in thepresence of potassium bis(trimethylsilyl)amide provided 39% yield of 174 <1998JMC1092>(Equation (34)).
SO O i. (Me3Si)2NK
ii. PhN(SO2CF3)2
Cl39%
S SCF3
O O O O
ClSMe SMe
173 174
ð34Þ
Trimethylsilylmethyllithium added smoothly to trifluoromethanesulfonyl, nonafluorobutane-sulfonyl, tridecafluorohexanesulfonyl, and heptadecafluorooctanesulfonyl fluorides to providethe corresponding methane derivatives 175. Treatment of these compounds with 2 equiv. ofBuLi followed by quenching of the generated dianions with one of the mentioned sulfonylfluorides provided anion 176. The corresponding free acids 177 were obtained in high yields(72–95%) by vacuum sublimation from concentrated sulfuric acid (Scheme 31). A series offluorous tris(perfluoroalkanesulfonyl)methanes was prepared in this way and catalytic activityof their lanthanide(III) salts was studied <1999JOC2910, 2000SL847, 2002T3835>.
Reaction of 3 equiv. of nonafluorobutanesulfonyl fluoride with 4 equiv. of methylmagnesiumchloride provided the corresponding magnesium salt 178 and its acidic hydrolysis gave 179<1999SL1990> (Scheme 32).
The reaction of sulfinate anions with thiophosgene has been discovered <1980OPP229>. In thecase of 1-adamantyl derivative 180, tris(adamantylsulfonyl)methane 181 was obtained in 39%yield <1992SUL(15)209> (Scheme 33).
6.03.3.3.3 Oxidized trithio-ortho-esters containing at least one sulfonate group
This was duly reviewed in COFGT (1995) <1995COFGT(6)67> and no substantial progress hasappeared since its publication.
i. 2 equiv. BuLi
ii. Rf2SO2F
Rf1 Rf
1S SO O O O
175
Rf1 Rf
1S SO O O O
SRf
O
O177
Rf1
Rf1
Rf2
S SO O O O
SO
O176
–Li+
H2SO4
72–95%2
Scheme 31
H2SO4 C4F9S S
C4F9
O O O O
SC4F9
O
O
(C4F9SO2)3CMgCl
178 179
C4F9SO2FMeMgCl
Scheme 32
AdS S
Ad
O O O O
SAd
O
O
(AdSO2)2CH-S-SO2Ad– S
39% 180
181
CSCl2AdSO2Na
Scheme 33
Functions Containing Three Chalcogens (and No Halogens) 97
6.03.4 FUNCTIONS BEARING THREE SELENIUM ATOMS
6.03.4.1 Methods for the Preparation of Triseleno-ortho-esters
6.03.4.1.1 Triseleno-ortho-esters from triselenacarbenium salts
New examples documenting the usefulness of this method have been published <1996JOC2877>.
6.03.4.1.2 Triseleno-ortho-esters from diselenoacetals and related compounds
1,3-Diselenane 182 treated with BuLi and MeSeSeMe provided excellent yields of the correspond-ing triseleno-ortho-ester as a single cis-isomer 183 having the MeSe group in equatorial position.This compound treated with lithium diisopropylamide and then with MeOH or MeI providedgood yields of the corresponding trans-derivatives 184 or 185 <1996TL8015> (Scheme 34). It wasnecessary to use potassium diisopropylamide (KDA) instead of BuLi to obtain similar PhSederivative which was obtained in 92% as a mixture of cis-trans isomers in a ratio of 98:2<1996TL2667>.
6.03.5 MIXED CHALCOGEN FUNCTIONS INCLUDING OXYGEN
6.03.5.1 Methods for the Preparation of Functions R1C(OR2) (OR3)SR4
6.03.5.1.1 From R1C(X1)(X2)X3
(i) From ortho-esters
Treatment of partially protected mercaptodioles or mercaptotrioles 186 with methyl ortho-formate in the presence of p-toluenesulfonic acid provided high yields (78–85%) of 187<1996JOC3604, 1997JHC909> (Equation (35)).
R
SH
OHTBDMSO (MeO)3CH
TBDMSO SO
R
OMe
R = H, TBDMSOCH2
78–85 %
186 187
ð35Þ
Reactions of electrophilic carbenes with thiocarbonyl compounds are believed to occur throughintermediate thiocarbonyl ylides <2000PJC1503>. Dimethoxycarbene formed by thermolysis ofoxadiazoline 188 was trapped with adamantanethione 189 to provide 92% yield of the first2,2-dialkoxythiirane described 190 <2001OL2455> (Equation (36)).
SeSe
i. BuLiii. MeSeSeMe
SeSe
H
SeMe
i. LDAii. MeOH
SeSe
SeMe
Me182 183
184
185
i. LDAii. MeI
SeSe
SeMe
H
81%
95%
93%
Scheme 34
98 Functions Containing Three Chalcogens (and No Halogens)
NN
O
OMeMeO
+92%
S S OMe
OMe
188 190
Heat
189
ð36Þ
(ii) From �,�-dihalothioethers
Acetylated dibromo derivative 63 treated with methanol, ethanol, or allyl alcohol in the presenceof silver triflate provided good yields of the corresponding acetylated o-thiolactones 191<1996CAR(282)237> (Equation (37)).
ROH, TfOAg
R Yield (%)90 69 70
abc
S
AcO OAcOAc
Br
BrS
AcO OAcOAc
OR
OR
63 191MeEt
Allyl
ð37Þ
Treatment of trichloro derivatives 192 with Na2CO3 in methanol led to selective replacement ofboth geminal chloro atoms to afford dimethoxy derivatives 193 <1994JOC6973> (Equation (38)).
SR
O
Cl Cl
SR
O
MeO OMeCl Cl
192 193
Na2CO3–MeOH
ð38Þ
(iii) From thioesters
Ozonolysis of 194 and 196 in CH2Cl2 at �78 �C followed by reduction with Me2S gave goodyields of cage compounds 195 and 197, respectively <1997T17653> (Equations (39) and (40)).
OAc
OSMe
RO
i. O3, CH2Cl2ii. Me2S
60–65 %
O
O
OO
O
R
SMe
194 195
ð39Þ
OSMe
RO
i. O3, CH2Cl2ii. Me2S
80–85 %
O
OO
O
R
SMe
CHO CHO
196 197
ð40Þ
(iv) From dithioesters
Aromatic dithioesters 198, which are easily available either from the appropriate nitriles or fromthe corresponding Grignard reagents, were transformed in high yields to 201 by treatment withsodium methoxide followed by iodomethane. Intermediate formation of 199 and 200 was sup-posed <1997MI3691, 2001T1289> (Scheme 35).
Functions Containing Three Chalcogens (and No Halogens) 99
6.03.5.1.2 Miscellaneous
Protected bromopyranones, e.g., 202 <1994BMC1309, 1998CAR(308)287, 2001JA3369> andfuranones 204, <1999OL1517>, treated with ethanethiol in the presence of 2,6-lutidine orcollidine, usually in nitromethane, provided high yields of 203 and 205, respectively. The similarphenylsulfanyl analog of 205 was found to be unstable <1999OL1517> (Scheme 36).
6.03.5.2 Methods for the Preparation of Functions R1C(OR2) (SR3)SR4
6.03.5.2.1 From R1C(X1)(X2)X3
Good yields of 2-methoxy-1,3-dithiane were prepared from 1,3-dithiane 60 by its sequentialtreatment with N-chlorosuccinimide (NCS) and methanol <1994SL547> (Scheme 37).
R1
SR2
S
MeONa
R1
OMe
S
MeONa
R1
MeO
OMe
S–Na+
MeI
R1
MeO
OMe
SMeR1 = Me, CH2 = CH–; R2 = Me, CH2COOH
198 199 200
201
Scheme 35
O Br
OAcAcOOAc
O
AcOOAc
O
O Me
SEt82%
EtSH
86%
EtSHO
O2CTol
O2CTol
Br
TolCO2
OO2CTol
O2CTol
O
O
EtS
202 203
204 205
Scheme 36
S SS S
Cl
MeOH S S
OMe70%
NCS
60 61
Scheme 37
100 Functions Containing Three Chalcogens (and No Halogens)
6.03.5.2.2 From dithiacarbenium salts
Hexathiaadamantane 171 in superacid media (e.g., CF3SO3H, FSO3H-SbF5, or H2SO4�SO3)formed carbodication 206, which treated with ice provided oxa derivative 207 <1999OL1771,2000JCS(P2)1777> (Scheme 38).
6.03.5.2.3 From dithioacetals and related compounds
Acid 208 treated with lead tetraacetate provided 60% yield of 209 <1994S167> (Equation (41)).
S
SCF3
COOH
Pb(OAc)4
60% S
S
O O
CF3
208 209
ð41Þ
6.03.5.2.4 From ketene dithioacetals
Intramolecular acid-catalyzed cycloaddition of hydroxysubstituted cyclic ketene dithioacetalswas first described by Corey and Beames as a method of lactone protection <1973JA5829>.Though the methodology is undoubtedly important, it was not mentioned in the correspondingchapter of COFGT (1995) <1995COFGT(6)67>. Therefore, some principal older papers will bealso reviewed here. Reviews on the ketene dithioacetals are also available <1977S357,1990S171>. Several useful applications of this cyclization protocol have been described since<1986JA5221, 1992JCS(P1)1901, 1993TL1035, 1993TL1039, 1996S285, 1997JOC9107,1998JCS(P1)9>. This reaction is a key step frequently used in the synthesis of a range ofnaturally occurring compounds. Transformation of mevinoline to its homolactone using ketenedithioacetal has been described <1982JOC4750>. This method was also used for the stereo-selective synthesis of a range of �-alkyl-�-butyrolactones 210 (Scheme 39). The method was alsomodified for the stereoselective synthesis of �,�-bis-functionalized �
˜-butyrolactones
<1993JOC2725>.
Similarly, the cyclization can also be used for the synthesis of functionalized �-lactones withremote asymmetric induction. Acid-catalyzed cyclization of ketene dithioacetals 211 by HCl/CH2Cl2 gave predominantly the �-isomers of the bicyclic dithio-ortho-esters 212 (Equation (42)).Hydrolysis (HgCl2, pH 7) then gave the corresponding lactones <1986JA5221, 1986TL3661>. Highyield of spirocyclic compound 214 with acceptable diastereomeric ratio (12:1) was also obtained byacidic cyclization of 213 (Equation (43)). The compound was used as an intermediate of thesalinomycin synthesis <1998JCS(P1)9>. A similar procedure was also used in the synthesis of akey synthetic fragment of rapamycin <1996SL903>.
S SS
SSS
S SS
SS
+
+S S
SS
OSH2O
206 207171
30%
Scheme 38
S
S
S
S
OR
OH R
71–95 %
TFA–CH2Cl2 HgCl2–aq. MeCN
O
R
O
210
Scheme 39
Functions Containing Three Chalcogens (and No Halogens) 101
S S 76% (R = H)92% (R = Me)
R
OS
SHCl–CH2Cl2
OSiMe3R
H
BOM
BOM
211 212
ð42Þ
S S81%
HOEt
HOO
S
S
H
OH
Et
HCl–CH2Cl2
213 214
ð43Þ
Even higher diastereoselection was reported in case of compound 215, where the stereocontrolwas by bromine and oxazolidine moieties <1996S285> (Equation (44)).
SS
47%
0 °C, 18 h
OH
BrN
O
O
O
BnOSS
HN
O
BrO
O
Bn
215
ð44Þ
Lactols 216 and 218 on reaction with 2-lithio-2-trimethylsilyl-1,3-dithiane followed by acidictreatment afforded high yields of 217 <1994TA247> and 219 <1996SL925> (Equations (45)and (46)).
+ S S
Me3Si Li
BDPSOOMOM
O
MOMO
OH
216
S SO
OMOMBDPSO
MOMO
217
83%
CSA, THFð45Þ
+ S S
Me3Si Li
OOH
COOEt
218
OS
S
COOEt
219
91%
HCl, dioxane
ð46Þ
A similar reaction was also involved in transformation of lactol 220 into a 2:1 mixture of thecorresponding aldehydes 221 and 222 <1998EJO275> (Equation (47)).
2:1
99% PPTSO
OH
S
S
220
+OS
S
CHO
221
OSS
CHO
222
ð47Þ
Intramolecular nitrone cycloaddition reaction of 223 led stereoselectively to a high yield of 224<2002OL1227> (Equation (48)).
102 Functions Containing Three Chalcogens (and No Halogens)
SS
HO
O
[3 + 2]
N+O–
Bn
NO
H
HBn
SS
O
O
223 224
ð48Þ
As reported earlier <1993TL2649>, bis-sulfonyl derivative 225 can be easily oxidized to givestereoselectively oxirane 226 (Equation (49)). Similarly, enantiomerically and diastereomeri-cally pure spirocyclic bis-sulfinyl oxiranes 228 (R=Ph, substituted Ph, cyclohexyl) wereprepared by stereoselective nucleophilic epoxidation of ketene thioacetal dioxides 227(Equation (50)). These novel epoxides represent potentially versatile chiral substrates for thepreparation of a variety of heterosubstituted carbonyl compounds <1998JOC7128,2002OL1227>. In these cases, the nucleophilic peroxide attacks the top face of the ketenedithioacetal, whereas the cycloaddition reaction of nitrone mentioned above attacks theopposite face.
Ph
SO2Me
O2S Me Ph
SO2Me
O2S Me
OH
225 226
87%
MCPBAð49Þ
70–98 %
H2O2 or TBHPS
SR
HO
O
SS
R
HO
Major Minor
+O SS
H
RO
O
O O
227 228
ð50Þ
Hetero Diels–Alder reaction of ketene dithioacetal 229 with 3-(benzenesulfonyl)-3-butene-2-onegave 91% yield of 230 <1991JOC4098> (Equation (51)). Similarly, 1-oxo-(E,E)-2,4-hexadienephosphonate with ketene dithioacetal 231 gave 232 <1995PS(103)259> (Equation (52)).
S S 91% OS
SCCl4, 25 °C+
PhSO2
O
PhSO2
229 230
ð51Þ
+P(O)(OMe)2
O
S S
231O
S
S(MeO)2(O)P
232
ð52Þ
Similar hetero [4+2]-cycloaddition reaction of 233 and silylketene dithioacetal 234 proceedsat room temperature to give dihydropyran 235 in good yield <2002JOC7303>. Similarly, 233with alkyne 236 provided 85% yield of the 2:1 adduct 237 as the only isolated product<2002JOC7303> (Scheme 40).
It has been established that the ketene dithioacetal group influences the stereospecificity ofanodic carbon–carbon bond formation. Earlier similar enol ether enol–ether coupling led to 1:1mixtures of stereoisomers <1992JA1033>. Anodic oxidation of 238 in the presence of THF ledto good yields of one stereoisomer of 239 (Equation (53)). In the case of five-membered product,only the trans-isomer was formed. Alternatively, the six-membered product was established asthe cis-isomer. No rational explanation of this fact has been found <2001OL1729>. Bridgedbicyclic product 241 was obtained in 75% yield by the same method from 240 <2001T5183>
Functions Containing Three Chalcogens (and No Halogens) 103
(Equation (54)). The suggested mechanism includes anodic oxidation leading to the formation ofa radical cation from the ketene dithioacetal, which in turn is trapped by the side-chain enolether. Following trapping by MeOH, loss of a second electron, and a second trapping withMeOH, finally afford the cyclization products with one dithio-ortho-ester group and one acetalgroup.
S
S
MeOH–THF8 mA, 2.2 F/mol
70–94 %n = 1, 2
OMe
S
Sn OMe
MeO
OMen
238 239
ð53Þ
S
S
MeOH–THF8 mA, 2.2 F/mol
75%
S
SOMe
OMeMeO
MeO
240 241
ð54Þ
Similarly, the reactions where the initial cation radical is trapped with oxygen nucleophileswere studied. For example, anodic oxidation of ketene dithioacetal 242 in methanol led stereo-selectively to 243. This methodology was used also for the synthesis of more substitutedcompounds 243 and preliminary results of the synthesis of �-lactones 244 were mentionedwithout any data concerning the stereoselectivity <2001OL1729, 2002JA10101> (Equations(55) and (56)).
S
S
HOn nMeOH
8 mA, 2.2 F/mol
S S
OMeO
70–94 %
n = 1, 2242 243
ð55Þ
S
S
N MeOH8 mA, 2.2 F/mol
S S
OMeO
30–67 %OR
R
OMe
244
ð56Þ
P(OEt)2
CHO
O
SiMe3
EtS
EtS O
P(OEt)2
O
EtS
EtS
Me3Si86%
O
P(OEt)2
O
EtS
EtS
SiMe3
SMe
O
P(OEt)2
OMe3Si
MeS
85%
O
P(OEt)2
O
O
(EtO)2PO
SiMe3
SMe
233
234 235
236
237
236
Scheme 40
104 Functions Containing Three Chalcogens (and No Halogens)
6.03.5.2.5 Miscellaneous
Deprotonation of sulfonyl oxirane 245 with butyllithium followed by addition of S-phenylbenzenethiosulfonate gave 69% yield of 246 <1998JCS(P1)4097> (Equation (57)).
PhO2SO
OO
i. BuLi, THF, –100 °Cii. PhSSO2Ph PhO2S
O
OO
PhS69%
245 246
ð57Þ
Nitroethene derivatives 247 undergo fast intramolecular cyclization in CF3SO3H to give dica-tions 248, which in the presence of MeOH provided good-to-excellent yields of the correspondingproducts 249 <2001EJO1525> (Scheme 41).
Selective protection of the hydroxyl groups in 2,3-dithiothreitol 250 as t-butyldimethylsilylethers followed by treatment with trimethyl ortho-formate in the presence of camphorsulfonicacid (CSA) gave 80% yield of 2-methoxy-1,3-dithiolane 251 <1996JOC3611> (Equation (58)).
HOOH
SH
HS
250
SS
OMe
TBDMSO
TBDMSO
251
i. TBDMSCl, imidazole, DMF; ii. HC(OMe)3, CSA, CH2Cl2
i, ii
80% ð58Þ
6.03.5.3 Methods for the Preparation of Functions R1C (OR2) (OR3)SeR4
No further advances have occurred in this area since the publication of COFGT (1995)<1995COFGT(6)67>.
6.03.6 MIXED SULFUR AND SELENIUM FUNCTIONS
6.03.6.1 Methods for the Preparation of Functions R1C(SR2) (SR3)SeR4
6.03.6.1.1 From dithioacetals
While tris(trifluoromethylsulfanyl)methylcyanide 66 was obtained in good yields by alkylation of65 (cf. Section 6.03.3.1.5), the corresponding seleno analog 252 was obtained only in 7% yield<1994CB449> (Equation (59)).
CNF3CS
F3CS SeCF3
F3CS
F3CSCN
i. NaHii. CF3SeCl
7%
25265
ð59Þ
NO2
S
RS
TfOH
S
SRN
HO H
n
n
MeOH
S
NHO
n
SR
OMe
R = Me, PhCH2CH2; n = 1– 4
247 248 249
+
+
Scheme 41
Functions Containing Three Chalcogens (and No Halogens) 105
Trans-2-methylseleno-1,3-dithiane 253 was prepared in 90% yield as a single isomer with themethylseleno group in equatorial position. The compound can be transformed to the cis-isomer 254similarly as described for the 2-methylseleno-1,3-diselenane 184 <1996TL8015> (Scheme 42).
6.03.6.2 Methods for the Preparation of Functions R1C(SR2) (SeR3)SeR4
No further advances have occurred in this area since the publication of COFGT (1995)<1995COFGT(6)67>.
6.03.7 MIXED OXYGEN, SULFUR, AND SELENIUM FUNCTIONS
Chloroform solutions of vinyl selenides 255 in the presence of catalytic amount of CF3COOHquickly cyclized to the corresponding 2-butylsulfanyl-1,3-oxaselenolanes; the major isomers 256were indicated by nuclear magnetic resonance (NMR) techniques <1997CL545> (Equation (60)).
Se
SBu
R
OH
CF3CO2HSe O
R
SBu77–88%
255 256
ð60Þ
A new convenient synthesis of dialkyldiselenides by photolysis of Barton PTOC esters 257in the presence of 258 provided adducts 259. Though the adducts were not isolated buthydrolyzed in situ with hydrochloric acid and then oxidized with air to the required disele-nides, the structure of 259 was firmly established by 1H-, 13C-, and 77Se-NMR <1996T11163>(Scheme 43).
REFERENCES
1967AG(E)443 D. Seebach, Angew. Chem., Int. Ed. Engl. 1967, 6, 443–444.1969S17 D. Seebach, Synthesis 1969, 17–36.1971TL2475 R. T. Wragg, Tetrahedron Lett. 1971, 2475–2478.1972CB487 D. Seebach, Chem. Ber. 1972, 105, 487–510.1972CB3280 D. Seebach, K. H. Geiss, A. K. Beck, B. Graf, H. Daum, Chem. Ber. 1972, 105, 3280–3300.1972HCA75 P. Stuetz, P. A. Stadler, Helv. Chim. Acta 1972, 55, 75–82.1973JA5829 E. J. Corey, D. J. Beames, J. Am. Chem. Soc. 1973, 95, 5829–5831.1975CC216 A. R. B. Manas, R. A. J. Smith, J. Chem. Soc.,Chem. Commun. 1975, 216–217.1977S357 B.-T. Groebel, D. Seebach, Synthesis 1977, 357–402.1977TL3549 P. C. Ostrowski, V. V. Kane, Tetrahedron Lett. 1977, 3549–3552.1980JOC740 R. Breslow, P. S. Pandey, J. Org. Chem. 1980, 45, 740–741.1980OPP229 N. H. Nilsson, A. Senning, Org. Prep. Proced. Int. 1980, 12, 229–230.1982JOC4750 T. J. Lee, W. J. Holtz, R. L. Smith, J. Org. Chem. 1982, 47, 4750–4757.
SS
i. BuLiii. MeSeSeMe
SS
H
SeMe
i. LDAii. MeOH
SS
SeMe
H90% 93%
253 254
Scheme 42
N SR1COO
+R2 OR3
Se
SeR1R2R3O
SN R1SeSeR1 + R3COOR2 +NH
S
257 258 259
Scheme 43
106 Functions Containing Three Chalcogens (and No Halogens)
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Functions Containing Three Chalcogens (and No Halogens) 109
Biographical sketch
Stanislav Radl was born in Pilsen, Czechoslo-vakia. After graduation from the Prague Insti-tute of Chemical Technology in 1976 hejoined the Research Institute of Pharmacyand Biochemistry in Prague. He received hisPh.D. in medicinal chemistry in 1984. From1985 to 2003 his positions included: researchscientist, senior research scientist, project lea-der and department head. He spent 1992–1993as a visiting scientist at the Hoffmann-LaRoche Research Center, Nutley, NJ. Besidesmedicinal chemistry, his research interestsinclude mainly synthetic aspects of variousnitrogen-containing heterocycles. He has co-authored many original articles on antibacte-rial quinolones, as well as several reviews onvarious aspects of this group of therapeuticagents. Dr. Radl has also written three chap-ters of Adv. Heterocycl. Chem. and one chap-ter of Comp. Heterocycl. Chem. 2nd edn. He isan editor of Collect. Czech. Chem. Commun.and contributing editor of Drugs of the Future.
Svatava Voltrova was born in Bohumın, shestudied at Prague Institute of Chemical Tech-nology, where she obtained an M.Sc. in 1985under the direction of Professor O. Cervinkaand Ph.D. in 1989 under the supervisionof Professor J. Kuthan. After spending1991–1992 at the Dyson Perrins Laboratory,University of Oxford under the direction ofProfessor J. E. Baldwin, she returned to Pra-gue and took up her present position as Assis-tant Professor at the Prague Institute ofChemical Technology. Her scientific interestsinclude chemistry of heterocyclic compounds,especially aminopyridines, and amidinium-carboxylates.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 75–110
110 Functions Containing Three Chalcogens (and No Halogens)
6.04
Functions Containing a Chalcogen
and Any Other Heteroatoms Other
Than a Halogen
A. M. SHESTOPALOV
N. D. Zelinsky Institute of Organic Chemistry, Moscow, Russia
6.04.1 FUNCTIONS CONTAINING CHALCOGEN AND A GROUP 15 ELEMENT 1116.04.1.1 Functions Bearing Chalcogen and Nitrogen 1126.04.1.1.1 Functions bearing oxygen and nitrogen 1126.04.1.1.2 Functions bearing sulfur and nitrogen 1246.04.1.1.3 Functions bearing selenium and nitrogen substituent 131
6.04.1.2 Functions Bearing Chalcogen and P, As, Sb, or Bi 1326.04.1.2.1 Functions bearing oxygen and P, As, Sb, or Bi 1326.04.1.2.2 Functions bearing sulfur and P, As, Sb, or Bi 1396.04.1.2.3 Functions bearing selenium and phosphorus substituent 143
6.04.2 FUNCTIONS CONTAINING CHALCOGEN AND A METALLOID AND POSSIBLYA GROUP 15 ELEMENT 144
6.04.2.1 Functions Bearing Chalcogen and Boron 1446.04.2.2 Functions Bearing Chalcogen and Silicon 1446.04.2.2.1 Functions bearing oxygen and silicon 1446.04.2.2.2 Functions bearing sulfur and silicon 1486.04.2.2.3 Functions bearing selenium and silicon 151
6.04.2.3 Functions Bearing Chalcogen and Germanium 1516.04.2.3.1 Functions bearing two oxygen and one germanium substituents 1516.04.2.3.2 Functions bearing one oxygen, one sulfur, and one germanium substituents 151
6.04.3 FUNCTIONS CONTAINING CHALCOGEN AND A METAL AND POSSIBLYA GROUP 15 ELEMENT OR A METALLOID 152
6.04.3.1 Functions Bearing Oxygen and a Metal 1526.04.3.1.1 Functions bearing two oxygens and a metal 1526.04.3.1.2 Functions bearing oxygen, silicon, and a metal 1526.04.3.1.3 Functions bearing oxygen and two metals 152
6.04.3.2 Functions Bearing Sulfur and a Metal 1526.04.3.2.1 Functions bearing sulfur, oxygen, and a metal 1526.04.3.2.2 Functions bearing two sulfurs and a metal 1536.04.3.2.3 Functions bearing sulfur, boron, and a metal 1546.04.3.2.4 Functions bearing sulfur, silicon, and a metal 1546.04.3.2.5 Functions bearing sulfur and two metals 154
6.04.3.3 Functions Bearing Selenium and a Metal 154
6.04.1 FUNCTIONS CONTAINING CHALCOGEN AND A GROUP 15 ELEMENT
Compounds of this class were described previously in reviews <1969ZC201, B-1970MI001,1971S16, 1977UK685, B-1979MI002, 1979T1675, 1985HOU(E5)3, 1995COFGT(6)103>.
111
6.04.1.1 Functions Bearing Chalcogen and Nitrogen
Functional groups bearing chalcogen and nitrogen are available by modification of precursors,which contain sp3- or sp2-carbon atoms, via cycloadditions or by other miscellaneous methods.This general order is adhered to throughout this section.
6.04.1.1.1 Functions bearing oxygen and nitrogen
(i) Functions bearing two oxygen and one nitrogen substituent
The functional groups containing two ether groups and one nitrogen atom bonded to an sp3-carbon atom are named acetalamides. They can be classified as acyclic acetalamides and cyclicacetalamides. This is a large class of organic compounds that is widely used in organicsynthesis.
(a) From sp3-carbon compounds. Ethyl orthoformate reacts with benzotriazole 1 to give(benzotriazol-1-yl)diethoxymethane 2 in 90% yield <1995H131> (Scheme 1). Diacetalamidessuch as 2 have been reported as convenient reagents for the syntheses of various organiccompounds <1998CR409>.
A general method for the masked formylation by the electrophilic reagent, viz., 1-(1,3-dioxo-lanyl-2-yl)-1H-1,2,3-benzotriazole 3, has been reported <2000JOC1886>.
Similarly to benzotriazole, imidazole 4 has been demonstrated to react with ethyl orthoformate togive diethylacetal 5, which was used for the synthesis of quaternized diethylacetal 6 (Scheme 2)<2002JAP2002105058>.
Treatment of lactams such as 7 with CH(OEt)3 leads to the formation of N-diethoxymethyl-substituted derivatives such as 8 (Scheme 3) <1995S168, 1996S1196>.
Similarly, ergoline-active analogs 10 were obtained from substituted indole derivatives 9<1995AP609>. Building units 13 have been produced by the reaction of compounds 11 and 12.This reaction takes place in the presence of TsOH in 1,4-dioxane at 20 �C (Equation (1))<2002S274>.
NH
NN
NN
N
EtO OEt
NN
N
O O
O
OOEt
(EtO)3CH, performance fluid
90%
, PF5080, ∆
75%
1
2
3
Scheme 1
N
NH
N
N
EtO OEt
EtN
N
EtO OEt
I–(EtO)3CH
+
45 6
EtI, AcOEt
Scheme 2
112 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
N
EtO OEt
R1
R2
N
OO
O
R1
R2
O OHOH
1112
13
+
R1 = COOEt, CN, CHO, CH(CN)2; R2 = H, Br, I
ð1Þ
A similar reaction has been used for the synthesis of indole derivatives <2000SL125,2000JMC4563>. Pyrrolidone-2 and valerolactone diethoxyacetal 15 have been obtained in60–70% yield by the treatment of compounds 14 with ethyl orthoformate (Equation (2))<2002DOK61>.
N
EtO OEt
ONH
O
1514
(EtO)3CH, TsOH
n = 1, 2
( )n( )n
ð2Þ
In the presence of MeONa or MeOLi in methanol, trichloropyrrole dimethylacetal 16 will reactto give pyrrolidin-2-one 17. The reaction is driven to completion by the elimination of threechlorine atoms (Equation (3)) <2001TL4573>.
NBn
O
Me
OMe
OMeNO
ClCl
Cl
Bn
1716
MeONa or MeOLi, MeOH
ð3Þ
Hydroxymethyldioxolanylfluorouracil 18 and other novel classes of 1,3-dioxolane nucleosideswere synthesized by a coupling reaction. Thus, 2-methoxy-4[[(t-butyldiphenylsilyl)oxy]methyl]-1,3-dioxolane or 2-methyl-1,3-dioxolane have been demonstrated to react with silylated 5-fluorouracil,thymine, cytosine, and 5-chlorocytosine in the presence of TMSOTf to give the corresponding1,3-dioxolane nucleosides <1995JOC1546>.
NH
ON
EtO OEt
CHOEt
O
N
EtO
R1
R
R2
OEt
NH
R1
R
R2
(EtO)3CH
(EtO)3CH
7
8
109
Scheme 3
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 113
O
OOH
N
NH
O
O
F
18
A new type of Morinclaparvin A 20 has been obtained from 1,2-dihydroxyanthraquinone 19(Equation (4)) <1995MI218>.
O
O OH
OH
R1
R1 OO
R1
R1
O
ONR2
19 20
R = H, Me; R1 = H, OH
ð4Þ
Stereoselective electrophilic addition (bromo-pivaloyloxylation) to 1-[3,5-bis-O-(t-butyldimethyl-silyl)-2-deoxy-D-erythro-pent-1-enofuranosyl]uracil has been used to produce 10-C-branched uracilnucleosides such as 21 (R=O-Piv) and, when combined with nucleophilic substitution usingorgano-aluminum reagents, provides a new C�C bond forming method at the anomeric positionto give compounds such as 21 (R=CH2CH¼CH2) <1995MI417>.
It was found that substituted pyrimidine nucleosides 22 exhibit a wide spectrum of biologicalactivities, for instance they have been proposed as antitumor drugs <1995JAP07109289>.
OTBDMSO
N
NH
O
O
R
TBDMSO
BrO
R5O
N
NH
R1
O
OR3
R4O
Br
R2
21 22
(b) From sp2-carbon compounds. Anilide 23 has been used for the synthesis of cyclic acetals.Primarily the oxygen in compound 23 was methylated on treatment with TfOMe to yield salt 24,which has been converted to diacetal 25 on further reaction with MeONa, which has beendemonstrated to react with dimethyl-L-tartrate to give a mixture of atropoisomers of cyclicdiacetal 26 (Scheme 4) <2001JA5130>.
N
But
MeO
N
But
MeOMe
N
But
MeOO
TfOMe MeONa
MeOH
23 24 25
N
But
MeOO
COOMeMeOOC
26
+
Scheme 4
114 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
Ethylene 27 was converted into aziridine diacetal 28 on treatment with tosylazide at room tempera-ture in acetonitrile. However, in this case acyclic compounds were also obtained along with aziridine 28<2001T3909>. Similarly, the corresponding aziridines, containing RFSO2 group, were obtained fromunsaturated compounds such as 27 on treatment with RFSO2N3 (Equation (5)) <2001T669>.
OTMS
OMe
Me
Me N
OTMS
OMe
Ts
Me
Me+ TsN3
CH3CN, rt
27 28
ð5Þ
Azaadamantane diacetal 30 was synthesized using the traditional method by the reaction ofazaadamantane 29 with propane-1,3-diol in benzene in the presence of TsOH (Equation (6))<2001JCS(P2)522>.
N
Me
MeMe
O N
Me
MeMe
O
O
29 30
HO(CH2)3OH, TsOH, benzene, ∆, 48 h
ð6Þ
(c) Cycloaddition methods. The Vilsmeier reagents, generated from N,N-dimethylformamideand oxalylchloride, have been demonstrated to react with N-phenacylacetylanthranilic acid 31 togive compound 32, which contains the diacetalamino fragment as a part of the bicyclic system(Equation (7)) <1996T753>.
COOH
NAc
Ph
O
N
O
O
O
Ph
OO
31 32
ð7Þ
1,3-Dipolar cycloaddition of nitrones such as 33 to dihydropyrrolediones such as 34 leads tothe formation of diastereomers such as 35 and 36 (Equation (8)) <1996JCR(S)466>.
N
O
O
EtOOC
MeO
PhN
NO
Ph
Ph
O
O
H
MeO
Ar
NO
NPhPh
O
OAr H
OMeO
ArCH=N-Ph ++
33 34 35 36
ð8Þ
The�-diazocompounds 37were transformed into isomunchnone derivatives of (5(S))-phenyloxazin-3-one and -2,3-dione (38 and 39), by treatment with aldehyde in the presence of rhodium(II) acetate(1 mol.%) with high diastereofacial selectivity and exo-selectivity though in comparatively moderateyields (Equation (9)) <1997TL4521>.
N
O
PhH O
O
OH
HO
OMe
H
38
N OHN2
OX
Ph
OH
H
37 39
N O
OX
OPh
NO2
HO
exo-II
or
4-R-C6H4-CHO,Rh2(OAc)4 (1 mol.%)CH2Cl2, rt
X = C=O, CH2; R = NO2, OMe
ð9Þ
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 115
Under Rh2(OAc)4 catalysis, substituted 2-amino-3-cyano-4,5-dihydrofurans will react with3 equiv. of (PhCO)2C¼N¼N to give furo[2,3-b]pyrans 40 (Equation (10)) <1998JPR51>.
O
R1
R2
CN
NR2 OO
R1
R2
NC
NR2
OPh
Ph
40
3(PhCO)2C=N=N +ð10Þ
The cycloaddition of 2-aza-1,3-dienes 41, which are readily available from carboxylic acids,gives 1,3-oxazinones 42 in good yields (Equation (11)) <1999TL7079, 2002S2043>.
OSi(CH3)2CMe3
NR1
CHOPriHN O
OR1
OPri
R2
+ R2CHO
41
42
ð11Þ
The Diels–Alder reaction of unsaturated compound 43 with azobutadiene 44 leads to theformation of tetrahydropyridine diacetal 45, which is the key compound in the synthesis ofent-Fredericamycin A (Equation (12)) <1995JA11839>.
EtO OEt
EtOOC
NOH
COOEt N COOEtSO2MeEtO
EtO
EtOOCi. 25 °C, 20 h, CH2Cl2ii. MeSO2Cl, Et3N
+
43 44 45
ð12Þ
Thermal hetero-[3+2]-cycloaddition of dipolar trimethylenemethanes (46 Ð 47), to N-acyl- orN-tosylimines 48 gives �-methylene-�-pyrrolidone acetals 49 in high yields (Equation (13))<1999CL879>.
O O
R1
R1
O
ON
R1
R2R3
NR3
R2O O
δ
δ
Heat
4647
49
48
ð13Þ
Pyrrolidone acetal 53 has been obtained by the reaction of unsaturated isocyanate 52 anddimethoxycarbene 51, which was generated from oxadiazoline 50 <1996JA12848>. Besides,oxadiazoline 50 has been demonstrated to react with azide 54 to give the indole acetal 55,which was used in the synthesis of alkaloid (�)-Tazettine (Scheme 5) <1998JA3664>.
The reaction of piperidinecarboxylic acid 56 with carboxylic anhydrides afforded spiropiper-idineoxazolines 57, which have been used in the synthesis of opioid agonists (Equation (14))<1999SL1923>.
116 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
N
PhHN COOH
Bn N
ONPh O
RO
R
O
Bn
+ (RCO)2O
56
57
ð14Þ
Nucleosides such as 58 undergo intramolecular cyclization by the action of [Pb(OAc)4/I2/h�] or[(diacetoxyiodo)benzene (DIB)/I2/h�] to give a mixture of anomers of spirouracil nucleosides suchas 59 and 60, containing the diacetalamide fragment (Equation (15)) <1997TL6421>.
O
RR3O
R4ON
HN
O
O
R5O R2
R1
O
RR3O
R4O N
HNO
O
R2
R1
O
O
RR3O
R4O
NNH
O
O
R2
R1
O
+
5859 60
ð15Þ
Under base catalysis, O-glycosyltrichloroacetimidates 62, themselves obtained from protectedglucose 61 and trichloroacetonitrile, undergo ring closure to give cyclic diacetals 63 (Scheme 6)<1994SL84>.
NN
O
MeO OMe
N
MeOOMe
O
MeO OMe
O
O
CON3O
O
TO
O
O
NMeO
OMe
O
OMeOMe
THPOO
O
MeO OMe NCO 52
50 +
5051
53
54
55
∆
Scheme 5
O
OHRO
YX
OH
OR
O
HORO
YX
OR
O
CCl3HN
O
RO
YX
OR
O O
CCl3H2N
CH2Cl2, CCl3CN, DBU
6162 63
Scheme 6
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 117
Tetrahydroquinoline diacetal 66 was synthesized by the reaction of compound 64 with unsatu-rated compound 65 (Equation (16)) <1999AG(E)1928>.
Cl
NH
ButO O
TBSO OMe
+
64
65
66
N
O
OTBS
OMe
ButO
ð16Þ
Under the action of Bu3S4H and AlBN in toluene, oxazolines such as 67 undergo stereoselec-tive reductive ring closure to give compounds 68 (Equation (17)) <2002TL6911>.
O RN
Ph
TBSOSePh
ON
O
O
Ph OTBS
R
67 68
ð17Þ
Spirocyclic diacetal 71, obtained via Scheme 7 from chiral compound 69, has been used in thesynthesis of the rennin inhibitor SPP-100 <2000TL10091, 2001TL4819, 2002EUP1215201A2>.Other epoxides similar to diacetals 71 are available from oxazolyloxiranes <2002OL1551>.
The general method for synthesis of cyclic diacetals is exemplified by the transformation ofcompounds 72. Lactam acetals 73 were obtained by the isomerization of phthalimidomethyle-neoxiranes 72 in the presence of Lewis acid. The reaction is driven to completion by the treatmentof the reaction mixture with Et3N resulting in the formation of lactam diacetals in 73–96% yields(Equation (18)) <1997S1077, 1998CC43>.
N
O
O
OR2
R1 N
O
OR2O
R1
N
O
O
72 73
R1 = R2 =, , , ;
ii. Excess, Et3Ni. Lewis acid, PhCl, 120–130 °C
ð18Þ
The reaction of �-hydroxyiminonitriles 74 with 2 equiv. of resorcinol or phluoroglucinol 75occurs in the presence of HCl and leads to the formation of benzofuro[2,3-b]benzofurans 76containing the diacetalamino fragment (Equation (19)) <1999S751>.
PhN
O
OH
PhN
O
OHO
NO
Ph
Br
69 70 71
i, ii iii
78% 60%
i. LDA, LiCl, THF, 0 °C; ii. allyl bromide, 0 °C; iii. NBS, DME-H2O, 0 °C
Scheme 7
118 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
R1
NOH
CN
R2
OH
OH O O
NH2
R2 R2
OHHO
R1
+ 2
74 7576
R2 = H or OH
i. HCl, Et2O, 0 °Cii. NaOH aq.
ð19Þ
(ii) Functions bearing one oxygen and two nitrogen substituents
Functions bearing two nitrogen and one oxygen substituents are known commonly as esteraminals. The main methods for synthesis of ester aminals are described in COFGT (1995)<1995COFGT(6)103>, and almost no new publications in this area have appeared since. Oxa-zoloisoindole 79, containing the aminyl fragment, can be obtained in a mixture with phthalimidederivative 80 by the treatment of compound 77 with t-butyl-2-aminoacetate 78. In the samemanner, compound 77 gives a mixture of oxazoloisoindol 82 and compound 83 on the reactionwith chiral N1,N2,N2-trisubstituted-1,2-propanediamine 81 (Scheme 8) <1995JOC6987>.
(iii) Functions bearing one oxygen, one sulfur, and one nitrogen substituent
Functional groups bearing oxygen, sulfur, and nitrogen are nonsymmetrical, and this reduces thenumber of synthetic routes available for their preparation compared to their symmetrical analogs.
(a) From sp2-carbon compounds. Alkenes 85 were obtained from the aldehydes by condensa-tion with [(4-methylphenyl)thio]nitromethane 84. The treatment of the electron-deficient alkenes85 with lithium t-butyl peroxide in THF at �78 �C according to a previously reported method<1990T7429> resulted in rapid epoxidation to give 2-(tolylthio)-2-nitrooxiranes 86 in good yields(Scheme 9) <1995JOC6431, 1999JCS(P1)937>.
A ring-intact oxazoloisoindole derivative was obtained through the reaction of triflate 87 withan excess of benzylmercaptan producing equal amounts of diastereomers 88 and 89 in 86% yieldand the ring-open product 90 in 9% yield (Scheme 10) <1995JOC6987>.
Under SnCl4 catalysis, thiophenol has been demonstrated to react with 1,2-unsaturated nucleo-sides 91 in the presence of N-bromosuccinamide to give substituted nucleosides 92 (Equation (20))<2002JOC6124>.
N
O
O
OTfN
O
OHN
But OOC
N
O
O
HN
COOBut
N
O
ONBut OOC
N(COOBut)2
N
O
O
N
COOBut
N(COOBut)2
NButOOC
ButOOC NHCOOBut
H2N COOBut
78
77
7980
82
81
83
+
+
Scheme 8
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 119
HN
O
O N
O
ROSPh
RO
NHN
ORO
RO
O
O
9192
ð20Þ
The reaction of compound 93 with 94 gave cyanine dyes 95 (Equation (21)) <2002DP143>.
N
Z
N
ZCl
R RI–
N
Z
R
Me
OH
N
Z
N
ZO
R R
NZ RMe
I–
+
i
i. pyridine, reflux
Z = O, S, Se; R = (CH2)nCH3
n = 1, 4, 9
93 94
95
ð21Þ
TolS NO2R
NO2
STol
O
RNO2
STol
O
O
Me
Me
O
OO
OMe
Me
Me R1
OH
RCHO +
i. But OK, ii. MeSO2Cl, Pri NEt, iii. ButOOLi
i, ii iii
84 85 86
R = Ar, , , (R1 = Me, Pri, Ph)
2
Scheme 9
N
O
OOTf
N
O
O
N
O
O
BnS
N
O
O
BnS
N
O
OSBn
87
88 89 90
OTf
–
BnSHPri NEt2
Scheme 10
120 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
(b) Cycloaddition methods. 1,2-Diaza-1,3-butadienes and 2-thiooxazolines or 2-thiothiazolineshave been used in the synthesis of spiroheterocyclic compounds. At room temperature in THF,compounds 96 react with 2-thiooxazoline 97 to give spiroheterocycles (98, x=0). Under the sameconditions, adducts 100 can be accessed by the reaction of compounds 96 with 2-thiothiazoline 99.The subsequent ring closure of adducts 100 occurs on heating in THF or DMSO to givespiroheterocycles (98, x=0) (Scheme 11) <2000SL1464>.
2-Thiobenzooxazolines 101 and alkenes 102 on photolysis undergo [2+2]-cycloaddition togive the spiroadducts 103. In the case of compound 104, containing the vinyl fragment(R=CH¼CH2), photocyclization affords the tetracyclic compound 105 (Scheme 12)<2002HCA2383, 1999JCS(P1)1151>.
Under Lewis catalysis by SnCl2 at �78 �C, spirocompound 106 stereoselectively reacts withoxirane 107 to give compound 108. Under these conditions, the trans-dimethyl fragment ofoxirane 107 undergoes inversion to the cis-dimethyl fragment (Equation (22))<2000HCA3163>.
R1O
O
NN
O
R2 R1OOCNH
HN R
OS
S
N
NHS
S
S N
X NH
NH
R1OOC
R2
O
NHO
S
99 THF, rt
97 THF, rt
i
i. THF, ∆ ; or DMSO, 65–70 °CX = O, S
96
100
98
Scheme 11
N
OS
OOR
N
OS
OO
N
O
O
S
O
N
O
OOR
R1 R2
R3
R4
R3
R4
R1
R2
101
+
102
103
hν
hν
104 105
Scheme 12
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 121
N
S O
S
Ph
H
H
N
S O
S
OPh
HH
OSnCl4, –78 °C
+
106 107 108
ð22Þ
Spiroheterocycles 111 are available from the reaction of phthaloyl chloride 109 with1,5-bisnucleophiles 110 (Equation (23)) <1998CC1459>.
COCl
COClO
SN
R
O
O
R
S PhHN
RSEt
+
109110
111
ð23Þ
(iv) Functions bearing one oxygen, one selenium, and one nitrogen substituent
Sodium selenocyanate stereoselectively reacts with D-glucopyranose 112 to give cis-1,2-fusedgluco-oxazolidine-2-selenone 113 as a single product. Also, gluco-oxazolidine-2-selenone 113was obtained with high stereoselectivity from compounds 114 and 115 (Scheme 13)<2000CAL397>.
Elemental selenium has been demonstrated to react with 1,2-dinitrobenzene 116 to give amixture of benzoselenazole 117 and benzimidazole 118 on further reaction with carbon monoxide(Equation (24)) <1996KTK374>.
NO2
NO2 Se
HN
Oii. CO
41% 22%
+
116117 118
N
NO
i. Se, H2O, Et3N, THF
ð24Þ
5-Alkylideneselenazolin-2-ones 120 were obtained by the reaction of 3-aminoalkynes 119 withelemental selenium and CO. Similarly, six-membered ring heterocycle 122 has been obtained fromhomopropargylamine 121 (Scheme 14).
O
OS
OO
O
Ph
PhO
Ph
H
H
O
O
OO
Ph
Ph
O Ph
OHC O PhOH
OOH
O
Ph
Ph
O
O
HNO
O
Ph
PhO
Ph
H
H
Se
KSeCN, AcNMe2
KSeCN, THF, AcNMe2
i. OsO4, Me-morpholineoxide, H2O, Me2CO
ii. KSeCN, THF, AcNMe2
112 114
115 113
Scheme 13
122 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
Under the basic conditions, the reaction of alcohol 123 with elemental selenium leads to theformation of 1,3-oxazine-2-selenone in high yield 124 (Equation (25)) <1997PS335>.
H3C NC
OH
SeO
NHSe, Et3N, THF
80%
123 124
ð25Þ
2-Oxoselenazolidine-4((R))carboxylic acid 127 has been reported as a stable seleno-containingphysiologically active compounds. It was obtained in 40% yield from selenocysteine 126 and1,10-carbonylldiimidazole (CDI). Selenocysteine 126 was generated in the reaction mixture by thereduction of diselenide 125 with NaBH4 (Scheme 15).
Complex of LiAlHSeH has been widely used for the synthesis of different seleno-containing com-pounds, including synthesis of Se-methyl-N-phenylcarbamate 129. LiAlHSeH 128 has been obtained bythe reaction of lithium aluminum hydride with black selenium powder (Equation (26))<2001JA8408>.
LiAlHSeH PhNH
O
SeCH3
i. PhNCOii. CH3I
128 129
ð26Þ
Selenocarboxylic acid was found to readily react with aryl-, acyl-, and arenesulfonyl isocyanatesto give the acylcarbamoyl selenides 130 <2001HAC250>.
R1 Se NHR2
O O
130
R1 = CH3, C4H9, 1-Adamantyl, Ar
R2 = C6H5, C6H4CO, 4-CH3C6H4SO2
i
2-Methylbenzselenazole was used for the synthesis of heptamethinecyanine dyes 131<2002DP143>.
R1NHR
NHBu
NRSe
O
R1
Se NBu
O
Se, CO, DBU, THF
rt, 1.5 h
Se (2 mmol.),CO (1 atm)
DBU, THF, rt
CuI (2 mmol.)
reflux
120
122
119
121
Scheme 14
Se Se
NH2H2NHOOC COOH
NaBH4
H2N
HSe
COOH
CDI Se
NH
O COOH
125 126 127
Scheme 15
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 123
N
Se
R
O CH3 Se
N
NSe R
R
I–
131
R = (CH2)nCH3
n = 1, 4, 9
10-�-Phenylselenouridines (132 and 133) have been obtained by the reaction of 20-ketouridinederivatives with PhSeCl in the presence of a base, or by addition of PhSeH to the correspondingnucleoside, containing unsaturated dihydrofuranic cycle<2000TL3643, 2001CEJ2332, 2002JOC6124,2002JOC7706>. Phenylselenonucleosides (132 and 133) are potentially useful precursors for thesynthesis of a variety of 10-modified nucleosides.
TIPDS - 1,1,3,3-tetraizopropyldisiloxane-1,3-diyl
O N
NH
OTIPDS O O
O
O
SePhO N
NH
O
ORO
RO
SePh
O
132 133
6.04.1.1.2 Functions bearing sulfur and nitrogen
(i) Functions bearing two sulfur and one nitrogen substituent(s)
Literature examples of acetalthioamides synthesis are much rarer than those of acetalamides.However, the methods for synthesis of acetalthioamides and acetalamides resemble each other inmany cases and sometimes are described in the same articles.
(a) From sp3-carbon compounds. A complex of quinuclidine and BF3 134 has been deprotonatedon treatment with BuLi/ButOK to give quinuclidine-2,2-diphenyl sulfide 136 in 52% yield on furtherreaction of the intermediate 135 with diphenyl disulfide (Scheme 16) <1999CC1927>.
(b) From sp2-carbon compounds. 2-(Dimethylamino)-2H-1,3-dithiolene 138 has been obtained bythe reduction of the 4-S-alkyl-1,3-dithiolium salt 137 with NaBH4 in EtOH. Compound 138 has beenshown to be a useful precursor for the synthesis of tetrathiafulvalenes (Equation (27))<1994JOC5877>.
N– BF3
NSPh
SPhN
– BF3
M
(PhS)2BuLi, ButOK
134 135 136
N+ +
BF3 Et2O
Scheme 16
124 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
EtOOC S
S
S
Me
NMe
MeCOOEtPF6
EtOOC S
S
S
Me
NMe
Me
COOEt H
NaBH4, EtOH
137
138
–
ð27Þ
Dithialenes, containing the piperidine fragment, were obtained similarly <1997S407>.Bis(alkylthio)carbene has been demonstrated as a novel convenient reagent for organic synth-
esis <2000T10101>. Bis(alklylthio)carbene 140 was generated from oxadiazoline 139 on heating,similar to dimethoxycarbene 51 generated from 2,2-dimethoxyoxadiazoline 50. Further rapidreaction of bis(alklylthio)carbene 140 with isocyanate 52 leads to the formation of pyrrolin-2-one tetrathioacetals 141 (Scheme 17).
Compounds 141 can also be accessed from acyl azides 142 and bis(alkylthio)carbene 140. Bythis methodology, various substituted pyrrolidines (143–148), including spirocondensed analogs,were obtained from the corresponding acylazides or isocyanates and bis(alkylthio)carbene<1999TL6891, 1999JOC1766>.
N
PrSSPr
O
RSSR
N
SS
O
SS
N
Ph SPrSPr
O
PrS SPr
N
Ph
O
SS
S S
N
O
O
PrSSPr
O
PrS SPr
N
O
O
PrSSPr
O
PrSSPr
143 144 145
146 147 148
The formation of heterocycles 151 and 154 can be exemplified by the reactions of the insitu generated nitrilium phosphane ylide complex 149, which leads to either 1,2,3-thiazaphosp-hole 151 via [3+2]-cycloaddition or to sulfanyl-1,2-thiaphosphiran-3-amine 154 via an
NN
O
RS SR
RS SR NCO 52
N
RS SR
SRSR
O
O
N3
Heat
139
140
141 142
140
Scheme 17
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 125
intersystem-transylidation-type reaction giving the 1,3-dipolar complex 152 that undergoesring closure to form intermediate 153 and subsequent decomplexation to givesulfanyl-1,2-thiaphosphiran-3-amine 154 as the final product (Scheme 18) <1999CC499>.
A mixture of diastereomeric �-lactams 157 is obtained by the reaction of thioketals 155 with thecomplex 156 (Equation (28)) <1994JOC7934>.
R NSMe
SMeN
(OC)5Cr
OPh
O
NPh
N
SMe
SMe
O R
+
155 156 157
Et2O, hν
CO, 2 atmð28Þ
Under zirconium catalysis, compounds 158 undergo stereoselective assymetrical intramolecular[3+2]-cyclization to give hydrogenated pyrazolines containing the dithioacetal fragment 159(Equation (29)) <2002JA13678>.
MeS S
NHN
NO2
R1 R2
N
HN
SS
NO2
H
HR1
R2
Chiral Zn cat.
158 159
ð29Þ
Under acid catalysis, compounds 160 undergo intramolecular ring closure to give hexahydro-pyrimidines containing a dithioacetal fragment 161 in 99% yield (Equation (30)) <1995TL6257>.
R2HN NH
S OR1
MeS SMe
HN
N
O
SR2
R1
SMe
SMe
160 161
ð30Þ
Pyrrolidine dithioacetals 164 were obtained by the [3+2]-cycloaddition of ylides 162 to ethyl-enes 163 (Scheme 19) <1995TL9409, 1996TL711, 1996TL3915>.
NCN
S
HP
SCH2Ph
Me2N
–PhCN
+ PhCH2CS(CH3)2N)C=S
–[W]
149 150149
151
152 153 154
[W] = W(CO)5
SP
RMe2N
PhH2CS
[W]
NP
S
NPh
N
R[W]
PhS
Me2NS P
R
[W]+
]+PhC N P
[W
R
+C N P
[W]
RN
+
NPh
R[W]PhC N P
[W]
R+
+
Scheme 18
126 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
At room temperature, compounds 165 undergo intramolecular ring closure to give 1,2-dihydro-azeto[2,1-b]quinazolines 166 (Equation (31)) <1997T13449, 2000JOC7512>.
N
SMe
SMe
NC Me
Ph
HR
N
NH
Ph
R
Me
SMeSMe
165
166
25 °C, 1 h
ð31Þ
The cycloaddition of dithioesters 167 to acids 168 using triphosgene as an activator gave4,4-bismethylsulfanylazetidin-2-ones 169 in good yields (Equation (32)) <2002T2215>.
NMeS
MeSR1 R2 COOH
N
R2
O
SMeSMe
R158–68%
+
167 168 169
Et3N, triphosgene, 0 °C, 12 h
R1 = Ph, CH2Ph, CH2COOMe, CH(Me)COOMe; R2 = OMe, OPh
ð32Þ
(ii) Functions bearing one sulfur and two nitrogen substituents
(a) From sp3-carbon compounds. Tris(azolyl) methylthiolates 170 have been obtained bythe reaction of the corresponding trimethylsilylazoles with [CF3S(NMe2)2]
+[CF3S]�
<2001AG(E)1247>.
X = CH, N
170
X
NN C S
3
CF3S(NMe2)2
+–
Pyrimidine 171 reacts with benzyl bromide to give benzyl-substituted imidazo[1,5-a]-1,3,5-triazine 172. The reaction proceeds via intramolecular ring closure at the sulfur atom and leadsto the formation of the imidazole ring <1995JMC3558>. Compound 172 is also accessible by thereaction of imidazotriazine 173 with benzyl bromide (Scheme 20).
Similarly, S-alkylquinazoline is obtained from benzopyrimidinethione and �-dimethylamino-1-chloroethane in the presence of a base <2002MI335>.
(b) From sp2-carbon compounds. Nitration of compounds 174 and 175 with 55% HNO3
yielded 2,2,4-trinitro-3-chloro-3-thiolene-1,1-dioxide 176 but its yield did not exceed 8%(Scheme 21) <2002MI1111>.
2-Hydrazino-2,3-dihydrobenzothiazoline 177 is widely used for the syntheses of heterocycles, azo-methines, and other compounds containing the benzothiazoline fragment (178–182). This compoundreacts in the same way as monosubstituted hydrazines (Scheme 22) <1999MI325, 2001MI129>.
S
SN
Me
SiMe3
S
SN
CH3
CH2
S
S
N
R1
R2
Me
CsF R2
R1
162 164
163
Hal
+–
+
Scheme 19
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 127
HN
NS NH2
ONHCHO
Me
HN
NH
NN
O
SMe
Me
Br
HN
N
NN
O
S
MeMe
i. Me3SiCl, (Me3Si)2NH, Pyii. K2CO3, MeOH
K2CO3, MeOH
171
173
172
Scheme 20
S
Cl NO2
O OS
Cl NO2
HONO O
S
NO2Cl
O2N
O2NO O
55% HNO3 55% HNO3
174 175176
Scheme 21
N
S
Me
NHNH2
N
S
Me
NH
NHC
Ar
N
S
Me
N
HN
H2N
O
N
S
Me
NHNHCH2NHN
N
N
S
Me
HN
NS
O
OH
OH
HO
HO
N
N
NH2
N
S
Me
NH
NS
Ar
O
i. ArCHO, AcOH, EtOH; ii. , HCHO, HCl, H2O;
i
ii
iii
iv. HSCH2COOH, Dioxan
i, iv
177
178 179 180
181 182
iii. CH2(CN)COOEt, EtO, K2CO3;
Scheme 22
128 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
Similar to 2-hydrazino-2,3-dihydrobenzothiazoline 177, imidazothiazoline hydrazide 183 hasalso been demonstrated to react with aromatic aldehydes to give substituted hydrazones<2002UKZ46>.
S
N
NH
NHNH2
O
183
5-Aminothiadiazolines 184 were obtained by the reaction of substituted thiosemicarbazide withtetracyanoethylene (Equation (33)) <1998PS141>.
RNHCNHNH2
SCN
CN
NC
NC
NN
SRHNCN
CN
EtOAc
20–23%+
184
ð33Þ
Heterocycles 186 and 187 have been obtained from dithiosemicarbazide 185, which wasproduced by the reaction of 1,4-dichlorophthalazine with thiosemicarbazide. Besides, compounds186 and 187 can be accessed directly from 1,4-dichlorophthalazine and thiosemicarbazide in onestep without isolation of compound 185 (Scheme 23) <2001IJC(B)500>.
The intramolecular 1,3-dipolar cycloaddition of the o-allenylaryl fragment to the betainefragment of thienopyrimidine 188 occurs on heating and affords framework compounds 189.Similarly, the intermolecular cycloaddition of maleineamide to thienopyrimidines 190 leads tothe formation of adducts 191 containing the bridging sulfur atom (Scheme 24)<1997JOC3109>.
3,3,6,6-Tetramethyl-1-thia-4-cycloheptane 192 reacts with isothiocyanates 193 in a ratio of 1:3on heating in an autoclave without solvent to form adducts 194 in 17–60% yield. The formationof the compound 194 can most plausibly be explained by a concerted [3+2]-cycloaddition(Scheme 25) <2000JOC8940>.
The highly reactive 4-phenyl-1,2,4-thiazoline-3,5-dione 195 has been demonstrated to interactwith 4-phenyl-1,2,4-triazoline-3,5-dione 196 as a dipolarophile to give cycloadducts 197 in excel-lent yields (Equation (34)) <1995T6651>.
NNH
N
NHNHC
NH
SNH2
CS
NH2 N
N
NN
NN
S
S
O
O
S
S
NN
N
N
NHHN
HNNH
S
S
S
S
CS2 ClCH2COOH
185
186187
KOH, EtOH NAOH, H2O
Scheme 23
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 129
NN N
S
N
Me Me
OO
O
PhS
N
O
O
Me
Me
Me
NN
N OO
Ph
( )n
( )n
+
195 196 197
n = 1, 2
ð34Þ
The reaction of 1,2-diaza-1,3-butadienes 198 with 2-thiooxazoline 199 in THF at 20 �C leads tothe formation of the spiroheterocycle 200 containing the CNNS-fragment (Equation (35))<2000SL1464>.
N
N
S
R1OOC
Me
O
RPG
N
N
S
R1OOC
Me
O
RH
N
N
S
PhR1OOC
Me
O
PhMe
N
N
PhR1OOC
MeMe N
OPh
O
O Me
H
H
SN
O
O
Me
( )n( )n
Deprotection
188 189
190 191
Toluene, ∆
63%
PG = protecting group, n = 1, 2
+
∆+
+–
–
Scheme 24
SNCS
R
SN
S
R
SN
S
R
S
NR
SN
S
R
N
N
R
SR
S
NCSR
NCSR
+120 °C
17–60%
R = Me, Ph
192 193
194
+ –
Scheme 25
130 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
O
R1O NN
O
R2
NH
OS
S
N
O
HN
R1OOC
HN
O
R2
+
198 199 200
THF, 20 °Cð35Þ
(iii) Functions bearing one selenium, one sulfur, and one nitrogen substituent
(a) From sp2-carbon compounds. N-Methylbenzoselenazole-2-thiones such as 201 have beenalkylated at the exocyclic sulfur atom by the strong alkylating agents such as diethoxycarboniumtetrafluoroborate, which was generated in situ from BF3�Et2O and triethylorthoformate, to affordcompounds such as 202 on further electrochemical reaction (Equation (36)) <2002JCS(P1)1568,2000MI92>.
Se
NMe
SSe
NMe
SEtSe
NMe
SEt
BF4201 202
+
CH(OEt)3, BF3·Et2O reflux
Electrochem
–
ð36Þ
6.04.1.1.3 Functions bearing selenium and nitrogen substituent
The salt 203 obtained via Scheme 26 has been used for the synthesis of 13C-labeled tetra-methyltetraselenafulvalene <2001MI1035>.
Spiroselenoamide 205 has been obtained in a mixture with compound 206 by the treatment ofcompound 204 with AgBF4 (Equation (37)) <2001CC1336>.
Se
N
N
SeMe
MeSe
N
N
SeMe
MeSe
N
N
SeMe
Me
+
204 205 206
·2BF4
AgBF4, toluene, ∆–++
ð37Þ
NH
NSe
SeH2N
O
Cl
NSe
Se O
NSe
SePF6
Se
SeSe
Se
*CH2Cl2 + 2Se
580–600 °C*CSe2
i. H2SO4ii. HPF6
* *
*
203
**+
+
–
ii. (EtO)3P/ toluene
i. H2Se, EtOH
Scheme 26
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 131
6.04.1.2 Functions Bearing Chalcogen and P, As, Sb, or Bi
6.04.1.2.1 Functions bearing oxygen and P, As, Sb, or Bi
(i) Functions bearing two oxygen and one phosphorus substituent
1,1-Diethoxyethylphosphinates and phosphonites have been demonstrated to be convenientreagents for the synthesis of different functionally substituted phosphoric acids and phosphinates.Some reactions of the synthons (207–209) are outlined below (Table 1). Final ketal-protectedphosphorus acids can be deprotonated on further treatment with 1–2 equiv. of trimethylsilylchlor-ide in CH2Cl2, containing up to 5% weight of ethanol, and stirring of the reaction mixture forseveral hours under argon at room temperature <1995TL9385>.
PHO
OEt(EtO)2C
R
(EtO)2C POSiMe3
OEt
R(EtO)2C P
O
OEtMe
R
207 208 209
R = H, Me
Table 1 Synthesis of functional phosphorus acids
Reactant Condition ProductDeprotectedproduct
N
NBn
BnBnN
Toluene 100 �C, 1 h, 60% PO
OEt
MeOEt
OEtBn-NH-CH2 P
O
OEtHBn-NH-CH2
Br Na, toluene 5–20 �C, 3 h, 80% PO
OEt
MeOEt
OEtPO
OEtH
CH2Cl
NHCl Cl
Na, toluene 0–20 �C, 3 h, 60% NHCl Cl
PO
OEt
MeOEt
OEt
NHCl Cl
PO
OEtH
EtOOC THF 60 �C, 3 h, 95% EtOOCPO
OEt
MeOEt
OEt EtOOCPO
OEtH
Cl
NO2
i. BuLi, THF, �78!0 �C, 1 h, 60%ii. Ni.H2, EtOH, rt, 90%
PO
OEt
MeOEt
OEtH2N
Cl
PO
OEtHH2N
Cl
132 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
1,3-Dioxalanes 210 have been phosphorylated by treatment with diethyl chlorophosphite.The reaction proceeds through oxidation of the phosphorus atom (PIII ! PV) in the presenceof an orthoester and carboxylic acids to give a mixture of exo- and endo-isomers of nucleosides211 and 212 (Equation (38)) <1996TL3497>.
O
O O
BTBDPSO
R OEt
O
O O
BTBDPSO
R(EtO)2(O)P
+(EtO)2PCl, CH3CN
O
O O
BTBDPSO
R P(O)(OEt)2
exo-isomer endo-isomer210211 212
R = H, Me, Ph; B = T, U, CBz, GBz, ABz
ð38Þ
Alkylation of the hypophosphorus acid derivative 213 with 4-iodobenzyl bromide has been used toobtain compound 214, which was used in the synthesis of aminocarboxylic acid 215 (Scheme 27)<2000BMCL2343>.
The phosphorylated analog of sialic acid was obtained from N-acetyl-�-D-mannosamine 216.Initially compound 216 has been phosphorylated by dimethyl[1-(bromomethyl)ethyl]phosphonate217 in the presence of indium to give the threo product 218, which undergoes subsequent ozonolysisto give �- and �-sialoside acid mixture in a ratio of 5:1 (Scheme 28) <1996JOC9538>.
Dialkoxymethyl(diphenyl)phosphine oxides 220 and aldehydes 221 undergo the Horner–Wittigreaction to give asymmetrical �-hydroxy carboxylic esters 224. The reaction proceeds throughintermediates 222 and 223 (Scheme 29) <1999MI2270>.
PO
HOEt
EtOEtO
Br, i
IPO
OEt
OEtOEt
R1HN COOR2
ii, iii
213 214
215i. NaH, THF, –10 °C to rt; ii. BOC-iodoAla-OMe, Zn, BrCH2Br, TMSCl;
iii. (2-furyl)3P, Pd2dba3, DMA–THF, 60 °C
R1 = Boc, Z; R2
= Me, Bn
O
OEt
EtOEtO
I
P
Scheme 27
O
HO
OH
PAcHN
OHHOOH
O
MeOOMe
ONHAc
HOHO OH
HO
BrO
PO
OMe
OMe
PO
OMe
OMe
CH2
OHAcHN
HOOHOHOH
+ i ii, iii
81% 90%
216 217
218
219
i. In, EtOH, H2O, 6 days; ii. O3, MeOH, –78 °C; iii. Me2S, MeOH, –78 °C to rt
Scheme 28
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 133
Synthesis of the 50-homologated H-phosphinate 228 was achieved as follows. The 50-homologatedphosphinate 225 was made available from boron trifluoride-catalyzed oxetane ring opening with aphosphinate-stabilized carbanion. Subsequent hydrolysis of the 30-benzoate followed by silylationyielded 226. Selective removal of the orthoester protecting group from 226 liberated the ethyl-H-phosphinate 227. Hydrolysis with triethylamine, water, and ethanol produced the correspondingH-phosphinic acid, which was re-esterified with allyl alcohol, using DCC as the condensing agent,to produce the allyl-H-phosphinate 228 (Scheme 30) <2001SL467>.
Compound 229 has been used for the synthesis of inhibitors of the bacterial cell-wall biosynthesisenzyme MurC <2001BMCL1451>. Hypophosphorus acid synthons 230 were used for the synthesisof phosphorylated oligonucleotides <1995SL703, 1998SL283>, carbohydrates <2001SL473>, andother organic compounds <1999SL1633, 2002SL525>.
PO
OEt
EtO
EtO
O SO
OPO
HOR1
R1O
R1O
R2
229 230
R1 = Me, Et, Ph; R2 = H, CH3
O
O
T
OBzOT
PO
EtO
EtO
EtOMe
OTBDPSOT
PO
EtO
EtO
EtOMe
OTBDPSOT
PO
EtO
H
OTBDPSOT
PO
O
H
PO
MeOEt
EtO
EtOMe+
225
226 227 228
i, ii
iii iv, v
i. NaOMe, MeOH, rt, 85%; ii. TBDPS-Cl, imidazole, DMF, rt, 91%; iii. Me3SiCl, EtOH, CHCl3, rt, 71%; iv. Et3N, EtOH, H2O, rt, 95–98%;
v. allyl alcohol, DCC, 2 mol.% DMAP, THF, rt, 69–73%
Scheme 30
POR
OR
O
PhPh
R1 O
H OH
R1
PO
PhPh
RO OROR
OR
R1
H OH
COORR1ADROK or ROLi
71–92%*+
220 221 222 223 224
AD-mix α[(DHQ)2PHAL] config. (S )
AD-mix β[(DHQ)2PHAL] config. (R )
Scheme 29
134 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
(ii) Functions bearing one oxygen and two phosphorus substituents
Tris(trimethylsilyl)phosphite 232 reacts with acyl halides 231 to produce 1-hydroxymethylene-1,1-bisphosphonic acids 233 on subsequent hydrolysis of the intermediates (Equation (39))<2001PIAWO0109146, 2001TL8475>.
O
R Cl ROH
PP
OOH
OHOHO OH
n-P(OSiMe3)3 61–98%
231
+
232
233
n = 2–6
R = Me, C5H11, C11H23, Ph, PhCH2, 4-MeOPh, 4-NO2Ph, 3-Py
i. THF, 25 °C ii. MeOH, 25 °C, 1 h
ð39Þ
A one-pot synthesis of methyl(benzyl)hydroxylbisphosphonic esters was achieved without a proticreagent which removes the unusual �-ketophosphonate step. Thus, reaction of P(OCH2Ph)3 withRCOCl (R=Me, Ph, Bu, CH2OMe) in MeOH or AcOH gave (PhOCH2)2P(O)C(R)(OH)P(O)(OCH2Ph)2 <1996PS295>.
Synthesis of compounds 234 (R1=H, NO2, halo, amino, C1–6-alkyl, C1–6-alkoxy, aryl, heteroaryl;R2=H, halo, amino, C1–6-alkyl, C1–6-alkoxy, aryl, heteroaryl; Y=O, S, NH, etc.; Z=C1–5-alky-lene, aminoalkylene, m, n=0–1) has been reported <2002GEP10114352>. Thus, chlorinationof 4-RC6H4CH2CH2CH2COOH with oxalylchloride followed by treatment with P(OSiMe3)3produced 4-RC6H4CH2CH2CH2C(OSiMe3)[P(O)(OSiMe3)2]2. Hydrolysis of the latter followedby treatment with NaOAc afforded 4-RC6H4CH2CH2CH2C(OH)[P(O)(ONa)(OH)][P(O)(OH)2](R=N(CH2CH2Cl)2).
R1
R2
YnZm
PO3H2
OHPO3H2
234
Every so often, directly carboxylic and aminocarboxylic acids can be used for synthesis of1-hydroxy-1,1-diphosphorus compounds instead of acyl halides. In these cases PCl3, POCl3,and PCl5 can act as chlorination agents and H3PO4 as a reagent for phosphorylation<2002PIAWO0290367, 2002JMC2185, 2000USP6143923, 2000JAP281690, 2003USP3013918,2001MIP2173321, 2002MIP2178793, 1998BRP2316945, 1998PIAWO9834940, 1998GEP(O)19737923,1997PIAWO9739004, 1995JOC8310>. A typical example of such reaction is presented below(Equation (40)).
HO P
P
O OH
OH
O OH
OH
H2N
H2N COOH57%
i. H3PO3 ii. PCl3iii. H2O
ð40Þ
A method of synthesis of radioiodinated aminobisphosphonates 235 (X=125I, 211At;Y=CH, N) has been described with active esters N-succinimidyl-3-(trimethylstannyl)benzoateand N-succinimidyl-5-(trimethylstannyl)3-pyridinecarboxylate as precursors. The isolated andpurified radiolabeled intermediates were coupled to give 3-amino-1-hydroxypropylidene-1,1-bisphosphonate [H2NCH2CH2C(PO3HNa)2OH] in high yields ranging from 60% to 97%<1999MI397>.
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 135
Y
HO P
P OHO ONa
OHO ONa
NH
O
Y235 236
P
PO
RORO
RORO
R = Me, Et, iPr
O
O
1-Hydroxybisphosphonates [(R1O)2P(O)]2C(OH)R3 (R1, R2=H, straight or branched C1–6
alkyl, benzyl, aryl, Na, Ca, Li, K; R3=C1–10 straight chain or branched alkyl, Ph, benzyl, aryl,amido, organothio, alkoxy) and substituted hydroxybisphosphonates were obtained by the reac-tion of anions of dialkyl phosphites with acid halides. It is preferred that this reaction takes placeat a low temperature in the presence of a base so that rearrangement to dialkyl(dialkoxypho-sphinyl)phosphates is minimized. Thus, KN(SiMe3)2-mediated reaction of (EtO)2P(O)H withhydrocinnamoyl chloride produced 60% of [(EtO)2P(O)]2C(OH)CH2CH2Ph along with 9% of[(EtO)2P(O)]2CHCH2CH2Ph, and 3% of ester <1996PIAWO9633199>.
The feasibility of synthesizing �-hydroxy �-alkyl-/aryl methylenebisphosphonates via Grignardaddition to tetraalkyl carbonylbisphosphonates was shown; and some current and potentialtherapeutic uses of bisphosphonates and phosphonocarboxylates were summarized <1999PS313>.
Synthesis of acylaminoalkanediphosphonates 239 with 41–87% yields was achieved by thereaction of acyl halides 237 with aminoalkyldiphosphonates 238 <2002MIP1333210>. It wasshown that mono-, di-, and trisodium salts of compounds 239 can be obtained depending uponthe pH of the media (Equation (41)).
O
Cl
R
HO P
P
O OH
OH
O OH
OH
NH
OR
( )n
HO P
P
O OH
OH
O OH
OH
NH2
( )n
+
237238
239n = 2, 3, 5
i. NaOH, H2Oii. HCl, H2O
ð41Þ
1-Hydroxyethylidene-1,1-bisphosphonic esters 240 were used as a precursor for selective synthe-sis of mono- or disalts of these esters (241 and 242) (Scheme 31). <2000S633>.
Arylcarbonylphosphonates 243 react with 2-isocyanato-4H-1,3,2-benzodioxaphosphorin-4-one244 to give bicyclic aryl bisphosphonates 247. Probably, this reaction proceeds through inter-mediates 245 and 246 (Scheme 32) <2002MI980>.
1,2-Dihydro-1,3-diphosphinine 248 and mesitylnitrileoxide 249 undergo chemo-, regio-, andstereoselective 1,3-dipolar cycloaddition to give cyclic allene 250 (Equation (42))<2000AG(E)1261>.
Me
HO P
P
O OR
OR
O OK
OR Me
HO P
P
O OR
OR
O OR
OR Me
HO P
P
O OR
ONa
O ONa
OR
KI NaI
R = Me, Et R = Me
241 240 242
Scheme 31
136 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
P
PBut
ButBut
But
C NMe
Me
MeO
P
PN
OBut
But
But
But
Me
Me
Me
+77%
248 249250
ð42Þ
(iii) Functions bearing one oxygen, one nitrogen, and one phosphorus substituent
Synthesis of the compound 253 was achieved by the reaction of diisopropylammonium salt 251with bis(diisopropylamino)(trimethylstannyl)phosphine 252 in the presence of MeONa in methyl-ene chloride (Equation (43)) <1998EJI1539>.
PSnMe3
N(Pri)2
N(Pri)2 PMeO
(Pri) 2N
N(Pri)2
N(Pri)2
(Pri)2N=CHClPO2Cl2 +90%
251 252 253
i. CH2Cl2ii. THF, MeONa+ –
ð43Þ
[3+2]-Cycloaddition of diazoketones 254 to compounds 255 leads to the formation of5-alkylidene-4,5-dihydro-3H-1,2,4-diazaphospholes 256 (Equation (44)) <1996T10053>.
(Pri)3Si CN2
CO
BuiO
PBui
SiMe3
X
NN
PO
But
Si(Pri)3
Me3SiOX
But
81–83%
254 255 256
+
X = Cl, SiMe3
ð44Þ
Atimicine A undergoes selective phosphorylation along formylamino group with hydropho-sphoryl compounds 258. The reaction is driven to completion by the elimination of the formyl groupresulting in the formation of compounds 259 containing NHCH(OH)P fragment (Equation (45))<1996KFZ31>.
R = Me, Et; Ar = 4-ClPh, 1-naphthyl
Ar POR
O
OOR
O
OP
O
O
NCO
NP
OO
O
O
O
Ar
P
OOR
OR
+
Benzene, 80 °C8 h, argon
60–70%
243 244 245
246 247
OP
O
O
NCO
Ar
O
PO
OROR
+ –
OP
O ON
ArP
O
OROR
O
–
+
Scheme 32
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 137
O
OO Me
Prn
OMe(H2C)5
O Me
O
NH
O
OHNHCHO
O
OO Me
Prn
OMe(H2C)5
O Me
O
NH
O
OHNH
OH
PO
OR
OR
PO
H OROR
MeOH+
58–81%
257
258
259
R = Et, Ph, H
ð45Þ
Phosphorylated oxazoloisoindole 262 has been obtained by the reaction of phthalimide 260with diethylphosphonate 261 (Scheme 33) <2000PS107>.
Similar phosphorylated oxazoloisoindole 264 can be accessed by the enantioselective reaction ofaminoalcohol 263, phthalic anhydride, and Ph2PH <2001TA923>.
(iv) Functions bearing one oxygen, one sulfur, and one phosphorus substituent
Derivative of pulegone 265 gives compound 266, containing oxygen, sulfur, and phosphorus at ansp3-carbon atom, on the chain of subsequent reactions with BuLi, ClPPh2, and BH3�SMe2<2000JA10242>. Reaction occurs stereoselectively with retention of configuration of the startingreagent 265 (Equation (46)).
S
OMe
Me
Me
S
OMe
Me
Me
PPh
PhBH3
265 266
81%
i. BusLi, –78 °C ii. ClPPh2, –78 °C to rtiii. BH3·SMe2
ð46Þ
N
O
O
Br N
OPOEt
OEtO
O
N
OPPh
OPh
Pri
Pri OHNH2
PO
OEtOEt
H+
i. NaTHF; ii. THF; iii. NH4Cl, H2O; iv. Phthalic anhydride, xylene; v. TsCl, CH2Cl2, Py; vi. Ph2PH, KH, THF
86%
93%
260
261
262
263
264
i, ii, iii
iv, v, vi
Scheme 33
138 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
6.04.1.2.2 Functions bearing sulfur and P, As, Sb, or Bi
(i) Functions bearing two sulfur and one phosphorus substituent
The reaction of complex 267 with ylides 268 or with phosphine R3P and carbon disulfide yieldedthe salt 269, which was acylated with acetyl chloride to produce tributylphosphonium salt 270(Scheme 34) <1996JOC9585>.
Dithioacetal formylphosphonates 273 have been obtained by the reaction of disulfides 272 with�-phosphorylcarbenes, generated from the corresponding diazocompounds 271 <1996S1232>.Cyclic dithioformylphosphonates 274 and 275 were made available by the introduction of thecyclic disulfides in this reaction (Equation (47)).
R1 = Me, Et; R = Me, Et, Pr, Ph, 4-MePh, COOEt
O
PSR
SR
OR1O
OR1
(R1O)2PCHN2 + R-S-S-R
4–93%
273271 272
BF3·Et2O, CH2Cl2, 25 °C
ð47Þ
S
SPO
MeO
OMe
S
SPO
MeO
OMeSS
274 275
General methods for the synthesis of optically active �-phosphoryl sulfoxides 277 have beenreported. Compounds 276 have been subjected to lithiation and methylsulfonation with MeSO2SMeat P- and S-linked carbon atom to give �-phosphoryl sulfoxides 277 (Equation (48)) <1997T2959>.
R1 = Me, Et; R2
= Me, Ph, 4-MePh
P SR2
O
R1O
R1O OP S
R2O
R1OR1O
SMe
O
276 277
i. BunLiii. MeS(O)2SMe
ð48Þ
Phosphonate bisdisulfoxide 278 can be accessed by the recently developed method. This reagentcan be used for asymmetric synthesis of �-aminoamides <1998JOC7128, 1999PS337>.Compound 278 was obtained as shown in Scheme 35.
R3PS
S
SZrCp2Cl
SR3P
HBu3P
S
S
Me
OO
Me
Cl
267269
[Cp2ZrHCl]n
268
i. CS2;ii. R3P
R = Me, Bu. 270
+ –
Scheme 34
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 139
Compounds 280 and 281 were obtained in high yields by hetero-Diels–Alder reaction ofphosphonodithioformate 279 with cyclic dienes <2000TL7327> (Scheme 36).
Phosphorylated crown ethers 286 have been obtained by the reaction of compounds 282–285and triethoxyphosphine. Ethers 286 are convenient reagents for the synthesis of crown ethers oftetrathiofulvalenes (Scheme 37) <2001EJO933>.
Reaction of 2-alkoxy-1,3-benzodithiolene 287 or 1,3-benzodithiolylium fluoroborate 288 withP(OMe)3 takes place in acetonitrile in the presence of NaI to give 2-dimethoxyphosphinyl-1,3-benzodithiole 289 in high yield (Scheme 38) <2002M1055>.
S
POPri
O
OPri
MeS
S
POPri
O
OPri
MeS
Me
Me
P CS
SMeO
PriOOPriCH2Cl2
Cyclopentadiene CH2:CMeCMe:CH2,
THF
279281280
Scheme 36
SO
O
OSO
S
S
(OEt)2P
H
O
SO
O
OSO
S
SS
SO
O
OSO
S
SMeS
SO
O
OSO
S
SMeS
282
286
285
283 284
i, ii, iii
ii, iii
75%
75% ii, iii75%
75%iii
i. CF3SO3Me, CH2Cl2, EtOH; ii. CF3SO2H, MeCN; iii. P(OEt)3, MeCN
SO
O
OSO
S
SCF3SO3
–
Scheme 37
S S
POEt
O OEt
OOS S
POEt
O OEt
S S
[O]
43–58%
278
i. Chlorosuccinimideii. P(OEt)3
Scheme 35
140 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
Phosphorylated 1,3-dithiolenes 291 have been isolated as side products in the synthesis oftetrathiafulvalene derivatives 292 from acetylenes 290, CS2, and P(OMe)3 (Equation (49))<2002JHC691>.
S
SP
OMeOMe
R
Ph S
SR
Ph
S
S R
Ph
RPh
36 –37%
290 291 292
+
R = H, COOMe
i. CS2 ii. P(OMe)3iii. MeOH
ð49Þ
Thiphosphirane 154, containing a CPNS fragment, can be prepared by the method shown inScheme 18.
(ii) Functions bearing one sulfur and two phosphorus substituents
A methanediphosphonic ester, containing 4-MeSC6H4-S group 295, has been prepared by recentlydeveloped method, which is based on the reaction of compound 293 with disulfide 294 in thepresence of ButOK <1998JAP10130284>. Salt 296 has been obtained on further hydrolysis of theester 295 (Scheme 39) <1999JAP11080176>.
Initial exploratory results on the [4+2]-cycloaddition potential of the hetero-1,3-diene systemof 297 were provided by the reactions between the heterocyclic compounds 297 and the phos-phoalkynes 298. It was shown that the intermediate 299 reacts with one more molecule ofR�C�P to form compound 300, which then reacts with elemental sulfur to give compound301 in high yield (Scheme 40) <2002EJO1664>.
( PrOi)2P P(OPri)2
OO
MeS
S S
SMe
(PriO)2PS
(PriO)2PO
O
SMe
PO3HNaS
PO3HNaMeS
+
ButOK, PhMe
i. MeOH, HClii. NaOH, H2O
293 294 295
296
Scheme 39
i. HBF4, Ac2O; ii. Et2O; iii. P(OMe)3, NaI, MeCN
S
S O
Me
Me
S
S POMe
OOMe
S
S
BF4
i, ii, iii iii
287 289 288
82% 82%–
Scheme 38
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 141
(iii) Functions bearing one sulfur, one nitrogen, and one phosphorus substituent
The reaction of the unsaturated compound 302 with dimethyl diazomethane 303 leads to theformation of pyrazoline 304 stereoselectively, which has been used in cyclopropane synthesis(Equation (50)) <1999T14791>.
P SOO
EtOEtO
Tol-p
NNP
O
EtOEtO
MeMe
SO
Tol-p
302303
+ Me2CN2
304
Et2O, rt, 6 h
ð50Þ
Isothiazolylphosphonate 305 has been demonstrated to react with an ethereal solution ofdiazomethane to give a mixture of the two tautomers of 1- and 2-pyrazolines 306 and 307(Equation (51)) <2001T5455>.
SN
Ar NEt2
O OPO
EtO
EtON
SNN
PEtO
OEtO
Ar
OO
NEt2
NS
HN
N
NEt2
P
OEtOEtO
OO
Ar
Et2O
305 306 307
++ CH2N285%
total yield
Ar = 4-MeOPh
ð51Þ
1,4,2-Oxazaphospholine 309 has been prepared by the [4+1]-cycloaddition reaction of hetero-diene 308 with 4-chlorobenzenethiol and triethyl phosphite (Equation (52)) <1995ZOB948>.
Ph N CF3
ClO
P
N
OPh
EtO OEtOEt
F3CS
Cl
i, ii
308 309
i. 4-Cl-C6H4SH, KOH; ii. P(OEt)3, CH2Cl2
ð52Þ
P
P
P
SBut
But
But But
S P
P
SP
R
R
RC P P
P
P
SR
R
PR
R
P
P
P
SR
R
R
RC PToluene, 100 °C
86–92%
1/8, S8, Et3N,
toluene, 25 °C81%
R = But, Me2CEt, Me-c-Hex
+
297 298 299 300
301
Scheme 40
142 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
6.04.1.2.3 Functions bearing selenium and phosphorus substituent
(i) Functions bearing two selenium and one phosphorus substituent
Triselenocarbonate 310 has been used in the synthesis of 2-triphenylphosphino-1,3-diselenoletrifluoroborate 311. Compound 311 has been prepared by a one-pot reaction (Scheme 41)<1996JOC2877>.
Similar to sulfur-containing compounds 273, seleno-containing analogs 313 were obtained fromdiazocompounds 271 and diselenides 312 (Equation (53)) <1996S1232>.
O
PSeR
SeR
OR1O
OR1
(R1O)2PCHN2 + R–Se–Se–R
313271 312
R1 = Me; R = Ph; –R-R– = –CH2CMe2CH2 H2CH(But)CH2–
BF3·Et2O, CH2Cl2, 25 °C
, –C–
ð53Þ
(ii) Functions bearing one selenium and two phosphorus substituents
1,2,4-Selenodiphospholes 314, RC�P and elemental Se were used as precursors for the synthesisof 5-seleno-1,4,7,8-tetraphosphatetracyclo[4.3.0.02,4.03.7]non-8-enes 315 (Equation (54))<1999S1642, 2000CC1745, 2001HAC406>.
P
P
P
Se
P
PP
SeButC P + Se
315
+
314
But But
But
ButBut
Butð54Þ
(iii) Functions bearing one selenium, one sulfur, and one phosphorus substituent
Phosphonates, containing sulfur and selenium atoms 317, have been obtained by the reactionof �-phosphoryl sulfoxides 316 with phenyl selenobromide <1995TL2871, 1997T2959>. As inthe case of the sulfuric analogs <1997T2959>, this reaction occurs stereoselectively(Equation (55)).
(R1O)2PO
R
SO
Me
(R1O)2P
R
S
O
Me
PhSe
O
317316
i. BuLi, THFii. PhSeBr
ð55Þ
+
Se
SeE
ESe
Se
SeE
ESeMe
Se
SeE
E
SeMe
H
CF3SO3Me NaCNBH3i. HBF4, Et2Oii. Ph3P
310 311
Se
SeE
E
PPh3
H BF4–
+
Scheme 41
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 143
6.04.2 FUNCTIONS CONTAINING CHALCOGEN AND A METALLOID AND POSSIBLYA GROUP 15 ELEMENT
6.04.2.1 Functions Bearing Chalcogen and Boron
Only one example of the synthesis of compounds bearing two boron atoms and one oxygen hasappeared in the literature since COFGT (1995). The reaction of 1,2-bis(diisopropylamino)-2,5-dihydro-1H-1,2-diborole 318 with carbon monoxide leads to the formation of the product 319.Similarly, compound 321 can be obtained from unsaturated 1,2-diborole 320 (Scheme 42)<1998EJI459>.
6.04.2.2 Functions Bearing Chalcogen and Silicon
6.04.2.2.1 Functions bearing oxygen and silicon
(i) Functions bearing two oxygen and one silicon substituent(s)
[(3-Benzyltetrahydro-2-furanyl)(dimethoxy)methyl](trimethyl)silane 323 has been obtained fromcompound 322, Ph3P
+CH2OMeCl�, and Me3SiCl by the electrochemical reaction. Alsocompound 323 was synthesized using acyclic monomers. This reaction occurs stereoselectively(Equation (56)) <2002JA10101>.
O O
Ph
O
Ph
SiMe3
OMeOMe
322 323
i ii iii
i. Ph3P+CH2OMeCl–; ii. Me3SiCl; iii. 0.5 M Et4NOTs, MeOH, 8 mA, 2.0 F/mol
80%
ð56Þ
In the presence of tertiary amine, compound 324 undergoes nucleophilic substitution by phenolor benzylalcohol at a bromine-linked carbon atom to give asymmetric trimethylsilyl acetals 325,which are also accessible directly from silyl methyl ether 326 without preliminary isolation ofcompound 324 <2001TL4557>. Furthermore, compounds 325 can be obtained from 1-octanole(Scheme 43) <1999MI469>.
BB CH2
N(Pri)2
(Pri)2N BO
B O
B
B
N(Pri)2
N(Pri)2
N(Pri)2
N(Pri)2
N(Pri)2
CH2 N(Pri )2
CH2N
BB
N(Pri )2
N(Pri)2
BO
B OB
B
N
318
319
320
321
CO, THF
44%
CO, THF
50%
(Pri)2
(Pri)2
Scheme 42
144 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
1-Substituted-1-alkoxy-1,3-diene 327 has been brominated by N-bromosuccinimide to givecompound 328 on subsequent washing of the reaction mixture with sodium bicarbonate solution(Equation (57)) <1999SL1841>.
EtO
Me3Si CH2
Me3SiOMe
OMeBr
327 328
i. MeOH, bromosuccinimide, THF ii. NaHCO3, H2Oiii. Et2O ð57Þ
Mg-promoted cross-coupling reactions of aromatic carbonyl compounds 329 with trimethylsilylchloride in DMF at room temperature bring about reductive carbon–silicon bond formation togive the corresponding �-trimethylsilyl alkyltrimethylsilyl ethers 330 selectively in good yields(Equation (58)) <1995CL829>.
O
Ph OEt
PhEtO O
SiMe3
SiMe3
Me3SiCl, Mg, DMF
56%
329 330
ð58Þ
(ii) Functions bearing one oxygen and two silicon substituents
Epoxide 331 selectively reacts with Me3SiCl in the presence of BusLi to yield di-(trimethylsilyl)-epoxide 332 (Equation (59)) <2002PIAWO2002053549>.
O
(CH2)9-Me
O
(CH2)9-MeMe3Si
Me3Si52%
331 332
i. Me3SiCl, BusLi, hexane ii. THFiii. HCl, H2O ð59Þ
Silylation of epoxide 333 by Me3SiCl also selectively leads to the formation of 1,1-disilylepoxide 334 (Equation (60)) <2002SL553>.
OCH2But
ButMe
Me
OMe3Si
SiCH2
MeMe
i. TMEDA, BusLi, Et2O, cyclohexaneii. Me3SiCl
58%
333 334
ð60Þ
Allyl ether 337 can be accessed by the electrochemical reaction of compounds 335 and 336(Equation (61)) <2001JEC55>.
Br
MeO SiMe3
OR
MeO SiMe3MeO SiMe3
ROH, EtN(Pri )2
84%
i. Br2 ii. ROH, EtN(Pri)2
84%
324 325 326
R = Ph, Bu, 1-octane
Scheme 43
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 145
Me3SiOMe
SiMe3
Sn(Bun) H2C CHCH2SiMe3 Me3SiOMe
SiMe3
CH2+Bu4N+BF4 , CH2Cl2
98%
335 337336
–
ð61Þ
Substituted benzotriazole 340 containing the bis(trimethylsilyl)phenoxymethylene group hasbeen obtained by the reaction of 1-(phenoxymethyl)-1H-1,2,3-benzotriazole 338 with 2 equiv. ofMe3SiCl (Scheme 44) <1999T11903>.
The reaction of complex 341 with pivaldehyde afforded the di(hypersilyl)compound 342(Equation (62)) <1997CB1709>.
SiMe3SiLi
SiMe3
Me3Si
OO
O
ButCHOOH
Si(SiMe)3(Me3Si)3Si+
341
342
Pentane
ð62Þ
Oxidation of the unsaturated compound 343 by MCPBA in dichloroethane leads to theformation of epoxide 344 (Equation (63)) <1997JCS(P1)2279>.
(CH2)4COOMe
Me3Si
Me3Si OMe3Si
Me3Si(CH2)4COOMe
MCPBA, CH2Cl2
97%343 344
ð63Þ
Benzyl-N,N-diethylcarbamate 345 reacts with BuLi and trimethylsilyl chloride to give bis-silylated product 346 (Equation (64)) <1995SC3347>.
Et2N O
O
Ph Me3SiPh
SiMe3
OO
NEt2
BuLi, THFMe3SiCl
60%
345 346
ð64Þ
(iii) Functions bearing one oxygen, one sulfur, and one silicon substituent
The reaction of benzoquinones 347 or 348 with chloromethylenesulfinic acid 349 and subsequentsilylation of the reaction mixture yielded benzoxathiole 1,1-dioxides 350 (Scheme 45)<1996AP361>.
NN
N
CH2Cl
OH
NN
N
CH2OPh
NN
N
Me3Si OPh
NN
N
Me3Si OPhSiMe3
NN
N
CH2OPh
338
+NaH, DMF
85%
338 340339
i. LiN(Pri )2, THF
ii. Me3SiCl, THF
86%
i. LiN(Pri )2, THF
ii. Me3SiCl, THF
36%
Scheme 44
146 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
Substituted trimethylsilylmethane 352 has been obtained by consecutive reactions of the ether351 with ButLi, trimethylgermyl bromide, and trimethylsilyl chloride in THF (Equation (65))<2000JCS(P1)2677>.
OMeMe3Ge SPh
SiMe3
PhSCH2OMe
351 352
90%
i, ii, iii, iv
i. ButLi, THF; ii. Me3GeBr, THF; iii. ButLi, THF; iv. Me3SiCl
ð65Þ
(iv) Functions bearing one oxygen, one silicon, and one nitrogen substituent
1-(Chloromethyl)benzotriazole 353 has been lithiated by LDA to give 3,3-disubstituted-1-oxira-nylbenzotriazoles such as 354 on further reaction with ketones, which have been silylated bytrimethylsilyl chloride to yield substituted oxiranylbenzotriazoles such as 355 bearing oxygen,silicon, and nitrogen at an sp3-carbon atom (Scheme 46) <2003JOC407>.
Trimethylsilyl allylbenzotriazole 357, obtained by the silylation of the substituted benzotriazole356, has been demonstrated as a convenient reagent for the synthesis of carbonyl compounds(Equation (66)) <1995JOC7589>.
NN
N
EtO
NN
N
EtOMe3Si
356 357
Me3SiCl, BuLi, THF
ð66Þ
Some other benzotriazoles substituted with a trimethylsilyl group 358 have been obtained bythe reaction of methoxymethyl benzotriazole with alcohols and trimethylsilyl chloride<1999T11903>.
F
O
O
F
O
O
FSO
ClH2C OHS
OSiMe
MeBut
O O
F
MeO
+i, ii, iii, iv, v
72% 72%
i. HCl, H2O; ii. NaOH, H2O; iii. Me2SO4; iv. Li(Pri)2, THF; v. ButSiMe2Cl, HHF; vi. ButSiMe2Cl
i, ii, iii, iv, vi+
347348
349
349
350
Scheme 45
NN
N
CH2ClN
NN
OEt Et
NN
N
OEt Et
SiMe3
i. 3-pentanone, LiN(Pr-i)2, THF; ii. BuLi; iii. Me3SiCl; iv. BuLi, THF; v. Me3SiCl
i, ii, iii iv, v
353
354 355
69%
Scheme 46
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 147
NN
N
SiMe3RO
358
R = Ph, 4-MeOPh, Et, Me, But
The reaction of O-allenyl-�-D-xylofuranoses with Me3SiCl and ClSO2NCO afforded silylderivatives of �-D-xylofuranose 359 with high yields <2000TA3131>.
OO
OO
H
H
Me
Me
HN
O
CH2
Me3Si
OR
359
6.04.2.2.2 Functions bearing sulfur and silicon
(i) Functions bearing two sulfur and one silicon substituent(s)
2-Trimethylsilyl-1,3-dithiane 360 chemoselectively reacts with vinyl epoxides 361 to give com-pounds 362 (Equation (67)) <2002JA14516>.
S
S
SiMe3
O
RCH2
R
HO
CH2
S SSiMe3+
i, ii, iii
76–88%
360 361362
i. HMPT, ButLi, THF, hexane; ii. THF; iii. NH4Cl, H2OR = CH2OCHPh, CH2OSiBuPh2, cyclohexyl
ð67Þ
Substituted 2-silyl-1,3-dithianes have been obtained by various methods: the reaction of 2,4-dithiacyanopentanes with sodium in liquid ammonia and phenoxymethoxytrimethylsilylmethane<2002SL1447>, treatment of octanal with 1,3-dimercaptopropane and Me3SeCl <2002TA1825>,from 1,3-dithiane with diphenylfluorosilyl ether <2002JA7363>, by the reaction of 2-trimethyl-1,3-dithiane with triphenylsilyl ether of iodoethane <2002OL1787>, by silylation of 2-substituted1,3-dithianes with Alk3SiCl or disilylic ethers <2002OL2957, 2002S552, 2001CL476,2000TL321>, from 2-trimethylsilyl-1,3-dithianes with azulenes <2001S1346>, by the reaction of2-triphenylsilyl-1,3-dithianes with 5-bromopentanal acetal <2001JOC8983>, by the condensationof aromatic aldehydes with 1,3-dimercapropropane and subsequent silylation of the reactionmixture with Me3SiCl <2000JOM220>. Substituted 2-silyl-1,3-dithianes, obtained by these meth-ods, have been used for the synthesis of different derivatives of carbonyl compounds, includingnatural products. 2-Trimethylsilyl-1,3-dithiolane 366 has been obtained by the reaction of com-pounds 363, 364, or 365 with 1,2-dimercaptoethanol (Scheme 47) <2001TL4557>.
2-Acetylthiotetrahydropyran gives silylated 2-phenylthiomethylthiotetrahydropyran in 67%yield on reaction with chloromethylthiobenzene and Me3SiCl in THF <2002PS709>. The reac-tion of disilane 367 with diphenyldithiomethane 368 leads to the formation of bis(disilyl)ether 369(Equation (68)) <2000JOM12>.
148 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
SiCl
Me MeSiMe MeCl
SiMe MeSiMe Me
PhS SPh
PhS SPh
Bu, THF+
367
368
369
2PhSCH2SPh ð68Þ
1,3-Disilacyclohexanes 371 and 373 are formed by silylation of bis(alkylthio)methyllithium withchloro(chloromethyl)dimethylsilane 370 and 372 followed by ring closure in the presence of a base.The spiro-fused disilacyclohexane ring 373 is structurally strain free, like cyclohexane. The proposedreaction mechanism involves a silacyclopropane intermediate (Scheme 48) <1999ICA231>.
Norbor-5-en-2,3-dicarboximide 374 reacts with thiophenol and 2-methylsilyl-1,3-dithiane togive compound 375 (Equation (69)) <1998T12361>.
N
O
O
OMe
OMeH
H
SH
S
S
SiMe3
I IN
O
OMe
OMeH
HHO
S
S
Me3Si
+
374
375
+
ð69Þ
Me3SiCH2OMe
S
SSiMe3
OMe
Me3SiCHOBun
i. Br2; ii. BuOH, EtN(Pri)2; iii. HSCH2CH2SH, BF3-Et2O
i, ii, iii
ii, iii
iii
88%
363
364
365
366
Br
MeOCHSiMe3
Scheme 47
SiCH2Cl
Me Me
MeS SMe Si
SiMeS
MeS
MeMeSMe
SMeMe Me
S
S Si
Si
S
S
Me Me
Me Me
S
S
SiMe
MeCH2Cl
370 371
LiN(Pri)2, THF
LiN(Pri)2, THF
372 373
Scheme 48
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 149
(ii) Functions bearing one sulfur and two silicon substituents
Bis(trimethylsilyl)methane sulfonamide 377 has been obtained by the reaction of tris(trimethylsi-lyl)methanesulfonyl chloride 376 with H2O, PCl5, and piperidine (Equation (70)) <2000CJC1642>.
SiMe3
SiMe3
SiMe3
SO
OCl SN
O
O
SiMe3
SiMe3
376 377
i. H2O, THF ii. PCl5, Et2Oiii. Piperidine, CH2Cl2 ð70Þ
Reductive lithiation of (PhS)2CH(SiMe2)3CH(SPh)2 378 or deprotonation of PhSCH2(Si-Me2)3CH2SPh 380 has been used to afford PhSCHLi(SiMe2)3CHLiSPh, which was silylatedwith Me2SiCl2 or (SiMe2Cl)2 to give the tetrasilacyclohexane 381 or pentasilacycloheptane 379(Scheme 49) <1999SL1772, 2000JOM12>.
(iii) Functions bearing one sulfur, one silicon, and one nitrogen substituent
The lithiation site of 2-trimethylsilyl-N-BOC-pyrrolidine 382 is strictly dependent on the reactiontemperature; at �78 �C the anion of 382 reacts with dimethyl disulfide to give in solely 2,2-disubstituted product 383 (Equation (71)) <1999JPC455>.
NBOC
SiMe3 NBOC
SiMe3
SMe
76%
382 383
i. BusLi, TMEDAii. Me2S2 (–78 °C to rt)
ð71Þ
Nonregioselective reaction of 1-chloromethylbenzotriazole 384 with ButSH and Me3SiCl leadsto the formation of the mixture of compounds 385 and 386 (Equation (72)) <1999T11903>.
NN
N
CH2Cl
SHMe Me
Me NN
N
SBut SButMe3Si
NN
N
Me3Si
SiMe3
++
38480%385
10%386
i. NaH, DMF; ii. H2O; iii. CH2Cl2; iv. LiN(Pri)2, THF; v. Me3SiCl, THF; vi. NH4Cl, H2O, Et2O
(1) i, ii, iii(2) iv, v, vi
ð72Þ
SiMeMe SPh
SiMe MeSiMe
SPhMe
MeSi
PhSPhS Me
SiMe MeSiMe SPh
SPhMe
SiMeCl
MeSiMe MeCl
SiSi
SiSiSi
Me Me MeMe
MeMe
SPh
PhS
MeMe
Me Me
Me2SiCl2, BusLi
(4-ButC6H4)2.Li, THF+
380 381
378 379
PhSMe
Me
SPh
Me Me
MeSiSi
Si SiMe
Me
Me
Scheme 49
150 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
6.04.2.2.3 Functions bearing selenium and silicon
No new examples of the synthesis of the functional groups bearing selenium and silicon haveappeared in the literature since COFGT (1995) <1995COFGT(6)103>.
6.04.2.3 Functions Bearing Chalcogen and Germanium
6.04.2.3.1 Functions bearing two oxygen and one germanium substituents
Since 1994 only two examples of a functional group of such type have been reported. Reaction ofthe diazagermylenes 387 with dichlorocarbene leads to the formation of the mixture of com-pounds 388 and 389 (Equation (73)) <1998MI729>.
NGe
NSiMe3
SiMe3
NGe
NSiMe3
SiMe3
Cl
Cl
OBut OBut
OButNGe
NSiMe3
SiMe3
ClCHCl3, ButOK, hexane, pentane
+
387 388 389
ð73Þ
Unsaturated ether 390 reacts with tri-2-furylgermane to give t-butyldimethylsilyl acetal 391(Equation (74)) <2001MI461>.
OMe
OSiMe2But
But
RO GeH
+
390391
3O Ge
R
OMe
OSiMe2
3
ð74Þ
6.04.2.3.2 Functions bearing one oxygen, one sulfur, and one germanium substituents
Compound393, bearingoxygen, sulfur, andgermanium,hasbeenobtained in several stepsby the reactionof ether 392 with Me3GeBr and in one step from compound 394 (Scheme 50)<2000JCS(P1)2677>.
Compound 395 has been obtained in a similar way to the above-mentioned methods fromethers 392 and 394 (Scheme 51) <2000JCS(P1)2677>.
i. ButLi, THF; ii. Me3GeBr, THF; iii. NH4Cl, H2O
PhS-CH2-OMe Me3Ge COMe
SPhGeMe3
CH
OMeMe3Ge SPh
i, ii i, ii, iii i, ii, iii
(Step 1)92%392
393 394
Scheme 50
i. ButLi, THF; ii. Me3GeBr, THF; iii. Me3SiCl, THF; iv. NH4Cl, H2O
PhS-CH2-OMe Me3Ge COMe
SPhSiMe3
CH
OMeMe3Ge SPh
i, ii i, iii, iv i, iii, iv
(Step 1)392395 90%
394
Scheme 51
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 151
6.04.3 FUNCTIONS CONTAINING CHALCOGEN AND A METAL AND POSSIBLYA GROUP 15 ELEMENT OR A METALLOID
6.04.3.1 Functions Bearing Oxygen and a Metal
6.04.3.1.1 Functions bearing two oxygens and a metal
No new examples of the synthesis of the functional groups bearing two oxygens and a metal haveappeared in the literature since COFGT (1995) <1995COFGT(6)103>.
6.04.3.1.2 Functions bearing oxygen, silicon, and a metal
Methoxymethyltrimethyl silane 396 on treatment with BuLi undergoes regioselective lithiation togive in good yield 397 metallated at the methylene carbon (Equation (75)) <2000JOM87>.
MeOCH2SiMe3
LiBuLi, THF
95%396 397
MeOCHSiMe3 ð75Þ
6.04.3.1.3 Functions bearing oxygen and two metals
No new examples of the synthesis of the functional groups bearing oxygen and two metals haveappeared in the literature since COFGT (1995) <1995COFGT(6)103>.
6.04.3.2 Functions Bearing Sulfur and a Metal
6.04.3.2.1 Functions bearing sulfur, oxygen, and a metal
Compounds such as 399, bearing functional groups of this type, have been obtained by thereaction of trimethylsilyl ethers such as 398 with BuLi. Germanium-containing analogs such as401 were generated directly in the reaction mixture to give bisdigermenyl ethers such as 402 onfurther reaction with Me3GeBr or to give silylated compounds such as 403 on treatment withMe3SiCl (Scheme 52) <2000JCS(P1)2677>.
CH
Me3SiOMe
SPh CLi
Me3SiOMe
SPh
CH
Me3GeOMe
SPh COMe
Me3Ge SPhLi
CMe3GeOMe
SPhGeMe3
COMe
Me3Ge SPhSiMe3
Me3GeBr
BuLi, THF
ButLi, THF
92%
90%
398 399
400 401 402
403
MeSiCl
Scheme 52
152 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
6.04.3.2.2 Functions bearing two sulfurs and a metal
Compound 407, which can be used for the synthesis of macrolide antibiotic Roflamycoin, hasbeen obtained by the reaction of compounds 404–406 with BuLi (Equation (76))<1997JA2058>.
S
SSnBu3
SnBu3S
S
SnBu3O
OH OHO OH BuLi+ + LiCH2OCH2Ph
56%
404405
406407
Ph ð76Þ
Besides, 1,3-dithiane 404 has been converted into 2-deuterated-1,3-dithiane 408 bearing oneBu3Sn group <2001TL5001>.
S
SSnBu3
D
408
Dithioacetals such as 409 have been demonstrated to react with Bu3SnCl to give tributylstan-nylthioacetals such as 410, which can be used for the synthesis of �,�-unsaturated ketones(Equation (77)) <1995T2515>.
PhS CH
SPh
Ph(Bun)3Sn C
SPh
SPh Ph97%
409 410
i. BuLi, THF, hexaneii. Bu3SnCl
ð77Þ
Trimethylstannylthioacetal 411 undergoes Michael addition to 2-cyclohexenone to yield theketone 412 (Equation (78)) <2000AG(E)414>.
CH
SMeMeS SnMe3 O C
SMe
MeS SnMe3
2-cyclohexenoneHMPT, THF
77%
411 412
ð78Þ
By the reaction of pentadiene 413 with 2-methylene-1,3-dithiane 414, compound 415 has beengenerated in the reaction mixture and then alkylated to produce different dithiane polyenes 416and 417, which have been demonstrated to be convenient reagents for the stereoselective synthesisof decahydronaphthalenes (Scheme 53) <1995TL3473>.
Li-N,N-diisopropyl-3-amino-1,3-benzothiaborolide 418 has been prepared by the multistepsynthesis starting from thioanisole (Equation (79)) <1998JOM2379>.
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 153
Me S PhB
SLi
N(Pri )2
418
i, ii iii, iv v
i. BuLi, hexane; ii. Bu2SnCl2, pentane, hexane; iii. BCl3, pentane; iv. Pr2NH, CH2Cl2; v. ButLi, THFi
ð79Þ
6.04.3.2.3 Functions bearing sulfur, boron, and a metal
No new examples of the synthesis of the functional groups bearing sulfur, boron, and a metalhave appeared in the literature since COFGT (1995) <1995COFGT(6)103>.
6.04.3.2.4 Functions bearing sulfur, silicon, and a metal
No new examples of the synthesis of the functional groups bearing sulfur, silicon, and a metalhave appeared in the literature since COFGT (1995) <1995COFGT(6)103>.
6.04.3.2.5 Functions bearing sulfur and two metals
No new examples of the synthesis of the functional groups bearing sulfur and two metals haveappeared in the literature since COFGT (1995) <1995COFGT(6)103>.
6.04.3.3 Functions Bearing Selenium and a Metal
No new examples of the synthesis of the functional groups bearing selenium and a metal haveappeared in the literature since COFGT (1995) <1995COFGT(6)103>.
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158 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen
Biographical sketch
Anatoliy M. Shestopalov was born in Khmel’nyts’kyy, Ukraine, in 1954.He studied chemistry and biology at the Lugansk Pedagogical Institute,where he received his M.Sc. in chemistry and biology in 1979. In 1985he graduated with a Ph.D. (Development of the methods of synthesis,and investigation of chemical properties and biological activities of3-cyanopyridine-2(1H)-thiones and products of their transformation)from the Institute of Chemical Aids of Plant Protection in Moscow,Russia. After a postdoctoral stay at the Zelinsky Institute of OrganicChemistry in Moscow, he received his ‘‘Doctor of Science’’ degree inchemistry (Quaternized azines in the synthesis of carbo- and heterocycliccompounds) in 1991 at the Zelinsky Institute of Organic Chemistry. Heis now a chief scientist and head of the scientific group at the ZelinskyInstitute of Organic Chemistry.
His research interests include regio- and stereoselective synthesis ofcarbo- and heterocyclic compounds, multicomponent reactions, chemis-try of N-, O-, S-, Se-containing heterocycles and chemistry of physiolo-gically active compounds. He is an author of more then 200 scientificpublications.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 111–159
Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 159
6.05
Functions Containing at Least One
Group 15 Element (and No Halogen
or Chalcogen)
A. GUVEN
Anadolu University, Eskisehir, Turkey
6.05.1 FUNCTIONS CONTAINING THREE GROUP 15 ELEMENTS 1626.05.1.1 Functions Bearing Three Nitrogen Atoms 1626.05.1.1.1 1,1,1-Triaminoalkanes 1626.05.1.1.2 1,1,1-Trinitroalkanes 1666.05.1.1.3 1-Amino-1,1-dinitroalkanes 168
6.05.1.2 Functions Bearing Three Phosphorus Atoms 1716.05.1.3 Functions Bearing Three Arsenic Atoms 1756.05.1.4 Functions Bearing Group 15 Elements 1766.05.1.4.1 Functions bearing two nitrogen atoms and phosphorus atom 1766.05.1.4.2 Functions bearing two nitrogen atoms and one arsenic atom 1766.05.1.4.3 Functions bearing two nitrogen atoms and one antimony atom 1776.05.1.4.4 Functions bearing two phosphorus atoms and one nitrogen atom 1776.05.1.4.5 Functions bearing two phosphorus atoms and one arsenic atom 1806.05.1.4.6 Functions bearing two phosphorus atoms and one antimony atom 1806.05.1.4.7 Functions bearing two antimony atoms and one phosphorus atom 181
6.05.2 FUNCTIONS CONTAINING TWOGROUP 15 ELEMENTS ANDONEGROUP13 OR 14 ELEMENTS 181
6.05.2.1 Functions Containing Two Group 15 Elements and One Group 13 Elements 1816.05.2.1.1 Functions bearing two nitrogen atoms and one boron atom 1816.05.2.1.2 Functions bearing two nitrogen atoms and one gallium atom 1846.05.2.1.3 Functions bearing two nitrogen atoms and one indium atom 1846.05.2.1.4 Functions bearing two nitrogen atoms and one thallium atom 1876.05.2.1.5 Functions two phosphorus atoms and one gallium atom 1876.05.2.1.6 Functions bearing two phosphorus atoms and one indium atom 1886.05.2.1.7 Functions bearing one phosphorus, one nitrogen, and one boron atom 189
6.05.2.2 Functions Containing Two Group 15 Elements and One Group 14 Element 1896.05.2.2.1 Functions bearing two nitrogen atoms and one silicon atom 1896.05.2.2.2 Functions bearing two nitrogen atoms and one germanium atom 1896.05.2.2.3 Functions bearing two phosphorus atoms and one silicon atom 1906.05.2.2.4 Functions bearing two phosphorus atoms and one germanium atom 1916.05.2.2.5 Functions bearing two phosphorus atoms and one tin atom 1926.05.2.2.6 Functions bearing two antimony atoms and one silicon atom 1936.05.2.2.7 Functions bearing one nitrogen atom, one phosphorus atom, and one silicon atom 1936.05.2.2.8 Functions bearing one phosphorus atom, one antimony atom, and one silicon atom 194
6.05.3 FUNCTIONS CONTAINING ONLY ONE GROUP 15 ELEMENT 1946.05.3.1 Functions Bearing One Nitrogen Atom and Two Silicon Atoms 1946.05.3.2 Functions Bearing One Phosphorus Atom and Two Silicon Atoms 1956.05.3.3 Functions Bearing One Arsenic Atom and Two Silicon Atoms 1976.05.3.4 Functions Bearing One Antimony Atom and Two Silicon Atoms 1976.05.3.5 Functions Bearing One Bismuth Atom and Two Silicon Atoms 1996.05.3.6 Functions Bearing One Antimony Atom, One Gallium Atom, and One Silicon Atom 199
161
6.05.1 FUNCTIONS CONTAINING THREE GROUP 15 ELEMENTS
6.05.1.1 Functions Bearing Three Nitrogen Atoms
6.05.1.1.1 1,1,1-Triaminoalkanes
The use of a 2.1 molar ratio between conjugated azoalkenes 1 and diethylcyanomethylphospho-nate 2 in tetrahydrofuran (THF) at room temperature with a catalytic amount of sodium hydrideled to the direct formation of diethyl phosphonopyrrolo[2,3-b]pyrroles 4, via two sequential1,4-addition reactions 3 (Scheme 1) <1994S181>.
Reactions of 1-aryl-2-methylthio-4-(N-arylamino)-4-phenyl-1,3-diazabuta-1,3-dienes 7 with�-nitrosostyrenes 6, generated from �-chlorooximes 5 in the presence of sodium carbonate,resulted in the formation of a mixture of products which are easily separated, and characterizedas 1,4-diaryl-2-[N-arylamino(phenyl)methyleneamino]imidazole-3-oxide 8 and 1,4-diaryl-2-[N-arylamino(phenyl)methyleneamino]imidazole 9 (Scheme 2) <1999(JCS(P1)615>.
Tris(alkylpyrazolyl)methanes 11 were prepared from the corresponding pyrazoles 10 underphase transfer conditions in 35–67% yields (Scheme 3) <2000JOM120>. The reaction of tris(pyr-azolyl)methane 11 (R1=R2=H) with KOBut and paraformaldehyde followed by quenchingwith water yielded 12, which was then reacted with [Mn(CO)5SO3CF3], prepared in situ fromMn(CO)5Br and Ag(SO3)CF3, to afford complex 13 <2000JOM120>. The rhenium complexes oftris(alkylpyrazolyl)methanes 14 were prepared in refluxing toluene from the correspondingtris(alkylpyrazolyl)methanes 11 and Re(CO)5Br or Re(CO)5BF4 in 63–91% yield (Scheme 3)<2002JOM50>.
NaH
THFNN
R1MeO2C
H
Me
+ EtO PCNO
OEtC
N
N
Me
P
Me
OEtO
EtON
NHR1
NHR1
R
R
H
H
N
N
Me
Me
R
POEtO
EtOR
NH2
NHR1
NHR1
1 2
R = CO2Me
3 4
44–77%
R1 = CO2Me, CO2But,
CONHPh, CO2Et, CONH2
Scheme 1
ClC6H4-p-R3
OH
Na2CO3
NO
C6H4-p-R3
N
NPh
SMe
NHC6H4-p-R2
C6H4-p-R1
N
NHPh
SMe
NC6H4-p-R2
C6H4-p-R1
N
N
NC6H4-p-R2
O
Ph
NHp-R1-C6H4
C6H4-p-R3
N
N
NC6H4-p-R2
Ph
NHp-R1-C6H4
C6H4-p-R3
5 6
67
+
8 44–53%
9 31–38%
R3 = H, Cl, Me
R2 = H, OMe, Cl
R1 = H, Me
–+
Scheme 2
162 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
[4+1]-Cycloaddition reaction ofN-heterocyclic carbene, generated by thermal decomposition of 2-trichloromethyl-1,3-imidazolidines 15, which is readily available from the condensation of the vicinaldiamines and chloral, with isocyanates (16 and 17), obtained in situ via thermolysis of the readilyavailable acyl azides, afforded compounds (18–20) in 70–71% yields (Scheme 4) <2002MI4289>.
Mn(CO)5BrN N
N N
N NHOCH2 Mn CC
C
O
O
OOSF3CO
O
N N
N N
N NHOCH2 AgO3SCF311 +
R1 = R2
= H
Bu4NBr, Na2CO3, H2O
CHCl3, Et2O
HCHO, ButOK78%
12 13
Na2CO3, Bu4NBr
H2O, CHCl3rt then reflux, 3 days
N N
R2
R1
H
N
NHN
NN
N R2
R1
R2
R1
R2
R110
R1 = H, Me, Ph, Pri, But
R2 = H, Me
11
35–67%
n
–
+
2
Re(CO)5Br
Re(CO)5BF4
+
N N
N N
N NH Re CC
C
O
O
O
R R1
R2 R1
R2R1
X–11Toluene, reflux
63–91%
or
R1 = H, Me, Ph, Pri
R2 = H, Me, Pri
X = Br–, BF4
14
+
–
Scheme 3
∆xylene
80 °C, 2 hthen reflux 16 h
1819
=1
0.6N C O
N
N
H
CCl3
Ph
Ph
N N
O
ON
NPh
Ph
NO
NOH
H
Ph
N Ph
H
N C ON N
O
ON
NPh
Ph
16
15
71%18
1917
20
[4 + 1]-cycloaddition
70%
Scheme 4
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 163
Phenyl isocyanide reacted with the N,N-(dimethylamino)benzotriazolylcarbene 22, which wasgenerated from benzotriazol-1-ylmethylene-dimethyl-ammonium chloride 21, in a [1+2+2]-cycloaddition, and then with nucleophiles to generate various hydantoins 23 in a one-pot proce-dure (Scheme 5) <1996JHC1935>.
The methyl ester 27 was obtained in 80% yield in the presence of N-ethyldiisopropylamine(Hunig’s base) 26 from the reaction of phenyl isocyanide with salt 25, 1-amino-5-methoxycarbonyl-2,3-dimethyl-3H-imidazol-1-ium mesitylenesulfonate, which was prepared by direct amination ofthe 1,2-dimethyl-1H-imidazole-4-carboxylic acid methyl ester 24 with mesitylenesulfonylhydrox-ylamine (MSH) <1977S1> as the aminating agent (Scheme 6) <2001JOC8528>.
The cycloadducts tetrahydro-1H-[1,3,5]triazino[1,2-a]quiazoline-1,3-(2H)-diones 29 wereobtained from the reaction of 3,4-dihydroquinazoline 28 with phenyl isocyanate under mildconditions. When the reaction was carried out at temperatures above 110 �C in 1,2-dichloro-benzene containing excess of phenyl isocyanide afforded 30 in 53% yield (Scheme 7)<2000MI2105>.
The reactions of perfluoro-5-azanon-4-ene 31 with 2 equiv. of aniline and derivatives 32 in thepresence of Et3N afforded the corresponding quinazolines 33 in 67–72% yields. The treatment of31 with 2,6-dimethylaniline in a 1:1 stoichiometry afforded a six-membered heterocycle—thedihydroquinazoline derivative 34 in 61% yield. The reactions 31 with 1 equiv. of 2-nitro-, 4-nitro-, or pentafluoroaniline 35 produced the diazetine derivatives 36. The fluorine atom in C-4of 36 was substituted by the N-nucleophile to yield the compounds 37 in 57–68% yields(Scheme 8) <2000JFC263>.
NN
N
NHMe
MeCl–
NN
N
NMe
Me
N CPh OEt3N, benzene
N
NPh
Ph
O
NN
O
O
MeMe
2122
+morpholine
23
48%+
Scheme 5
MeCN20 h, rt
N
N
Me
Me
MeO2CMSH
N
N
Me
Me
MeO2CNH2
MSTSH
Pri
NEtPri N
N
Me
Me
MeO2CNH
N C OPhN
N
MeO2C
Me
N
NO
Ph
H
Me
N C OPhPri
NEtPri
N
N
MeO2C
MeN
Me
ON
PhO
H
Ph
24
CH2Cl2, rt93% MSTS = mesitylenesulfonate
25
25 +
26
27
80%
+
+
–
–
Scheme 6
164 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
The reaction of bis(dimethylamino)difluoromethane 40, which was produced from tetramethyl-chloroformamidinium chloride 39 and tetramethylammonium fluoride 38 in high yield, withdimethylaminotrimethylsilane, provided a rapid and facile access to hexamethylguanidiniumfluoride 41 in 95% yield. 1,1,1-Trifluoro-2,2,2-tris(dimethylamino)ethane 42 was prepared from41 and Me3SiCF3 in Et2O at �50 �C in 96% yield (Scheme 9) <2000JFC159>. Orthoamide 45was obtained from guanidininium chloride 43 and appropriate carbanion 44 in high yield(Scheme 9) <2002ZN(B)399>.
The 1,3-dipolar cycloaddition reaction of various N-aryl-C-ethoxycarbonylnitrilimines 47, gen-erated in situ from ethylhydrazono-�-bromoglyoxylate 48, with 1,3,4-benzotriazepin-5-ones 46 inthe presence of Et3N regio- and chemoselectively afforded [1,2,4]triazolo[1,3,4]benzotriazepines 49in 18–44% yields (Scheme 10) <2002MI1545>.
N
NR1R2
N C OPh
N
NR1
R2
N
N
O
O
Ph
H Ph
N
N
NOO
Ph
R2
R1N
O
Ph
28
+ 29
R1= Me, 4-Me-C6H4
R2 = H, Me
48–83%
Et2O, 0 °C
53%
110 °C, reflux
30
1,2-Cl2C6H4
R1 = 4-Me-C6H4
R2 = Me
Scheme 7
MeCN, Et3N
40 °C, 3 h
N C4F9F3CF2CF2C
F+
NH2
R N
N
R
CF2CF2CF3
NH
CF2CF2CF3
R
N
N
CF2CF2CF3
NH
CF2CF2CF3
Me
MeMe
NH2
MeMe
ArNH2+Et3N
MeCN
NN
F
F3CF2CF2C Ar
CF2CF2CF3 ArNH2N
N
NHAr
F3CF2CF2C Ar
CF2CF2CF3
R = H, F, OMe
2 equiv.
31 32
33
67–72%
34
61%31 +
31
Ar = 2-NO2-C6H4, Ar = 4-NO2-C6H4, C6F5
57–68%35
36 37
MeCN, Et3N
Scheme 8
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 165
6.05.1.1.2 1,1,1-Trinitroalkanes
The photolysis of tetranitromethane (TNM) 51 with 4-chloroanisole 50 in CH2Cl2 led to theformation of mainly 4-chloro-2-trinitromethylanisole 52 in 40–50% yields (Scheme 11)<1993ACS925>, with 1-methyl-4-propenylbenzene 53 to 1-methyl-4-(2-nitro-1-trinitromethyl-propyl)benzene 54 <1998ACS745>, with 2,8-dimethyldibenzofuran 55 to mainly (50%) 2,8-dimethyl-3-trinitromethyldibenzofuran 56 <1997ACS476>, with 1,4-dimethoxynaphthalene 57
Et3Nbenzene
1 week, rt18–44%N
NN
O
R1
Me
H
R2
NH
N CO2Et
BrNH
NN
O
R1
Me
N
NN
OMe
NN
CO2Et
R2
R1H
NEtO2C N R2+N
NN
O
R1
MeCO2Et
N
NH
R2
46
R1 = H, Ph
R2 = Me, Cl, NO2
47
48
In situ
49
+ –
Scheme 10
MeNMe MeMe
FCH2Cl2
95%0–5 °C, 5 h
NCl
NMe Me
Me
Me
+
Cl–
NN
N
Me
MeMe
Me
MeMe
F
NN
N
Me
MeMe
Me
MeMe
Cl
NF
FN
Me
MeMe Me
Me2NSiMe3
MeCN
Me3SiCF3
Et2ONNCF3
N
MeMe
MeMe
Me
Me
C C HCOSiMe3
EtEt
+ C C CCMe3SiO
EtEt N
NN
Me Me
MeMe
Me
Me
40
0 °C, 2.5 h95%
39
4196%
42
–50 °C
43
NaH, THF
94%
4445
38
+
+
+
+
–
–
–
Scheme 9
166 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
to 1,4-dimethoxy-2-trinitromethylnaphthalene 58, 1,4-dimethoxy-2-nitro-1-trinitromethyl-1,2-dihydronaphthalene 59, and 1,4-dimethoxy-2-trinitromethyl-1,2-dihydro-naphthalen-1-ol 60(Scheme 11) <1997ACS1066>.
The reaction of �,�-unsaturated ketones of the adamantanes, 1-adamantan-1-yl-3-phenyl-pro-penone 62 and 1-adamantan-1-yl-4-phenyl-but-3-en-2-one 63 with trinitromethane 61 affordedthe corresponding trinitroketones, 1-adamantan-1-yl-4,4,4-trinitro-3-phenyl-butan-1-one 64 and1-adamantan-1-yl-5,5,5-trinitro-4-phenyl-pentan-2-one 65 in 61% and 93% yields, respectively(Scheme 12) <2001ZOR1872>.
The destructive nitration of polynitrocarbonyl compounds 66 with HNO3–H2SO4 at 0 �Cyielded hexanitroethane 67 in 18–80% yields. Yield increased with electron-donor groups on 66(Scheme 13) <1994ZOR29>. The compound 5,5-dinitro-6-(4-nitrophenyl)hexan-2-one 68 wasalso subjected to nitration with HNO3–H2SO4 to yield 1-nitro-4-(2,2,3,3,3-pentanitro-propyl)ben-zene 69 in 19% yield (Scheme 13) <1994ZOR1521>.
CH2Cl2
OMe
OMe
NO2
NO2
NO2
OMe
OMe MeO
OMe
NO2
O2N
NO2
NO2
OMe
OMe
O2N
OMe
MeO OH NO2
NO2
NO2
51+
57
33%
+
+
OMe
Cl
O2NNO2
NO2
NO2
CH2Cl2
OMe
Cl
NO2
NO2
NO2 Cl
OON
NO2
NO2
NO2
OMe
50
+ +
51 40%52
hν
Me
Me
+CH2Cl2
O2N
O2N
NO2
NO2
MeMe
CH2Cl2
O
MeMe
O
MeMe
NO2
O
MeMe
NO2
O
MeMeNO2
NO2
NO2
51
53 54
51+
55
56
50%
19%
5%
29%hν
hν
18%
58hν
6%
59
14%
60
Scheme 11
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 167
The addition of weakly nucleophilic alcohols even to unactivated alkenes was made feasible undermild reaction conditions by the simple use of BF3Et2O catalyst. The 2-(2,2,2-trinitro-ethoxy)-bicy-clo[2.2.1]heptane (2-alkoxynorbornane) 72 was prepared from bicyclo[2.2.1]hept-2-ene (norbornene)70 and 2,2,2-trinitroethanol 71 at room temperature in 31% yield (Scheme 14) <1997S1056>.
The condensation of the dialkyl aminomalonates 73 with 2,2,2-trinitroethanol 71 gave thecorresponding Mannich bases, 2-(2,2,2-trinitroethylamino)malonates 74 in 70% and 82% yields,which were nitrated with HNO3–H2SO4 to give dialkyl 2-nitro-2[N-nitro-N-(2,2,2-trinitroethyl)-amino]malonates 75 in 80% and 86% yields (Scheme 15) <2001ZOR207>.
The treatment of acetonitrile N-oxide 76 with trinitroacetonitrile 77 afforded 3-methyl-5-trini-tromethyl[1,2,4]oxadiazole 78 in 39% yield (Scheme 16) <2002ZOR1269>.
6.05.1.1.3 1-Amino-1,1-dinitroalkanes
The difluoroamines 81 were obtained in 20–70% yields from the reaction of dinitrocarbanions 79with difluoroaminating reagent 80 (Scheme 17) <1996DOK358>. The 1,3-dicarbanion 82 gener-ated from 1,1,3,3-tetranitropropane was also difluoroaminated by 83 to afford the geminal(di-fluoroamino)tetranitro compound 84 in 65% yield (Scheme 17) <1996IZV2689>.
Dioxane
rt
O
Ph
NO2
O2N HNO2
PhO
OPh
O2N
NO2
NO2
OPh
NO2NO2
NO261
62
61%
93%
63
64
65
Scheme 12
O2N
O2N NO2
O
R2
R1
HNO3
H2SO4C C
O2NO2N
NO2
NO2
NO2
O2N
HNO3
H2SO4
O2N
O2NO2N
NO2
NO2
NO2
6667
68 69
19%
R1 = H, R2 = Me
R1 = H, R2 = Et
R1 = H, R2 = But
R1 = H, R2 = CH2CH2CO2H
R1 = H, R2 = 3-NO2-C6H4
R1 = Me, R2 = Me
O2NNO2
NO2O
Me
Scheme 13
O
NO2
NO2
NO2NO2
O2NNO2
CH2OHCH2Cl2
+
7170 31%rt, 15 min
72
Scheme 14
168 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
The photochemical reaction of TNM 51 in CH2Cl2 orMeCNwith styrene (R=H), 4-methylstyrene(R=Me), 4-chlorostyrene (R=Cl), and 4-acetoxystyrene (R=OAc) 85 afforded two stereo isoxa-zolidines, 5-(4-R-phenyl)-2-[1-(4-R-phenyl)-2-nitro-ethoxy]-3,3-dinitroisoxazolidines 88, 3-nitro-5-R-phenyl-4,5-dihydroisoxazole 2-oxides 87, and 1-(4-R-phenyl)-2-nitroethanones 86 (Scheme 18)<1998ACS751>.
The selection of the olefin to form the nitronic ester 91 in the reaction with TNM 2 is a crucialfactor in the synthesis of isoxazolidines (92, 94, and 96). Bicyclobutylidene 89 is the compound forthis purpose. The compound 89 reacts with TNM even at 0 �C; the reaction initially gives a chargetransfer complex, which can be transformed into nitronic ester 91, which does not enter into 1,3-dipolar cycloaddition with a second molecule of olefin 89 at low temperatures (0–5 �C). Onlykeeping of the reaction mixture at room temperature resulted in 3,3-dinitroisoxazolidines 92(Scheme 19) <2002DOK210>. The reaction of TNM 51 and bicyclobutylidene 89 with methy-lenecyclobutane 93 (R=H) or methylenecyanocyclobutane 5 (R=CN) afforded the correspond-ing isoxazolidines 94 in 46% and 66% yields, respectively. The olefins 95 containing electron-withdrawing groups were also reacted with 91 to yield the 3,3-dinitroisoxazolidines 96 in 24–59%yields (Scheme 19) <2002DOK210>.
The aryl-O N,N-azoxy-�,�-dinitroalkanes 98 were prepared by nitration of the correspondingN-phenyl-N0-(�-hydroxyiminoalkyl)diazene N-oxides 97 in 60% yields (Scheme 20)<1994MI226>.
NO2
O2NNO2
CH2OHCO2R
CO2RH2N
MeCO2Na
O2N
HN CO2R
NO2
O2N
CO2R
HNO3–H2SO4
O2NN CO2R
NO2O2N
CO2R
NO2
O2N
+
7173
R = Me, Et
rtR = Me, 70%R = Et, 82% 74
0–5 °C, 1 h
75
pH = 4
Scheme 15
39%
1,3-DipolarNO2
O2NNO2
C N++ –
C NMe O
NN
O
Me
O2N
NO2O2N
7677
78
Scheme 16
MeCN
CH2Cl2– –
OSF OO
NF2O2N
NO2 NO2
NO2Li+ Li+ NO2
NO2 NO2
NO2
F2N NF2
20–70%NO2
RNO2
Na+–
OSF NF2
O NO2
RNO2
NF2MeCN
7
+
80 81R = CN, CONH2
8382
+
8465%
Scheme 17
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 169
Hexane
0 °C
1NO2
O2N NO2
NO2
+NO
ONO2
NO2O2N NO
OO2N NO2
O2N
H2CR2
R1
+ NO
OO2N NO2
O2N
R2 R1
8951 91
24 h
92
rt30 min
91 24 hrt
9596
24–59%
R+ NO
OO2N NO2
O2N
R
91
R = H, CN93
24 hrt
94
46–66%
R1 = H, R2
= CN
R1 = Me, R2
= CO2Me
R1 = H, R2
= CH(OEt)2
R1 = H, R2
= Ph
R1 = H, R2
= 4-pyridyl
+
–
Scheme 19
NN R
O NOH
NN
O NO2
NO2
R
9760%
98
R = CO2Et, Me, CH2Cl, CH2N3, CH2N(NO2)Me
i. NH4NO3–HNO3
ii. N2O4, ClCH2CH2Cl+
–
+
–
Scheme 20
R
NO2
O2N NO2
NO2
CH2Cl2
O
NO2
R
O NO
NO2
R
ON
NO2O2N
O
O2N
R
R
+
6–27%
4 –11%
18 –31%
R = H, Me, Cl, OAc
85
86
87
88
51
hν
+
–
Scheme 18
170 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
6.05.1.2 Functions Bearing Three Phosphorus Atoms
When the phosphaalkynes 99 were heated at 130 �C, or at 180 �C in a Schlenk pressure tube, inthe absence of a solvent, complex mixtures of products were formed from which the respectivetetraphosphacubanes 100 could be isolated in modest yields (8% and 2%) (Scheme 21)<1994S1337>. At higher temperatures for the cyclooligomerization, 101 were formed in 7%and 2% yields, respectively. Tetraphosphacubanes 100 could also be prepared from the zircone-cene complexes 102, obtained from 103 and 99, in higher yields (50–80%) (Scheme 21)<1994S1337>.
The treatment of t-butylphosphaalkynes with bis(cyclooctatetraene)zirconium 104 and hafniumcomplexes 105 afforded 106 <1995AG(E)81> and 107 <1995AG(E)2227> in 81% yield, whichwere then demetallated with hexachloroethane to give 1,3,5,7-tetraphosphabarrelene 108 in 88%yield (Scheme 22) <1995AG(E)81, 1995AG(E)2227>.
Tetraphosphabarrelenes 110 were formed nearly quantitatively by heating a pentane solution of2,4,6-tri-t-butyl-1,3,5-triphosphabenzene with phosphaacetylenes. Analogous reaction of tripho-sphabenzene with di(isopropylamino)phosphaacetylene 109 led to an unexpected product 111 inquantitative yield (Scheme 23) <1998MI2071>. The compound 109 reacted with the stericallyhighly substituted t-butylacetylene only at temperatures above 100 �C to yield tricyclic compound112 in 76% yield (Scheme 23) <2000S529>.
The unusual reaction of t-butylphosphaalkyne with diethyl phosphite 113 at room temperaturein the absence of solvent produced the primary phosphine 114 (Scheme 24) <1996ZOB522>.
The phosphaalkynes undergo spirocyclotrimerization with incorporation of the correspondingLewis acid to form the betaines 115, which was then treated with dimethyl sulfoxide (DMSO) inthe presence of t-butylphosphaacetylene as a trapping reagent to afford two isomeric phosphaalk-ynecyclotetramers having cage structures 118 and 119 (Scheme 25) <1996CB489>. The reac-tion most probably proceeds by way of the triphosphabenzenes 116 and 117, which cannot beisolated as such but can only be trapped by a homo-Diels–Alder reaction. When, however, thespirocyclic zwitterion 115was treated in the absence of a trapping reagent with an excess of DMSO at�78 �C, the tetra(t-butyl)hexaphosphadecadiene 121 could be isolated in 22% yield
Toluene25 °C
PP
R
R
P
P
PP
R
R
R
RHetero-Diels–Alders
C PR
P
PP
PR
RR
R
∆
∆
P P
PP
R R
R
R
Schlenk pressure tubeR = But,
R = Pet,
130 °C, 65 h, 8%
180 °C, 3.5 h, 2%
99
100
Schlenk pressure tubeR = But,R = Pet,
180 °C, 6 h, 7%200 °C, 3–5 h, 2%
101
R = But, Pet, 1-Me-Cp, 1-Me-Cy
[2+2]-Cycloaddition
50–80%
2Cl3CCCl3
Zr P
R
R
PClZr Cl C PR
102
–78 °C then rt+
103
THF, BunLi
Scheme 21
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 171
<2002MI2622>. Compound 121 can be viewed as a dimer of the initially formed spirodipho-sphete 120, which undergoes elimination of one molecule of di-t-butylacetylene. Tetracycliccompound 121 was formed more efficiently by reaction utilizing triphosphoryl metal complexessuch as trimethylstannyltriphosphole 122 <1999MI3143>. The compound 118 was also preparedfrom the reaction of t-butylphosphaacetylene with 116 in Et2O in high yield (96%)
–20 °C<10 min
But H2 equiv.
PP
PBut
But
But
P
R
P P
P ButBut
But
C PR
C PNPr
i
Pr
i
PP
PBut
N Pr
i
Pr
i
PBut
But
PP
But
But P
But
But
25 °C, 12 h
110
95% 111
112
Toluene, –20 °C, 5 days76%
109
R = But, 98%
R = Pent, 96%
Scheme 23
Na
1 weekC PBut
OPEtO OEtH
+ O PEtO
EtO But
PP O
OEt
OEt
H H
114113
Scheme 24
HfRR
ZrC PBut
PP
PBut
But
But
P
But
M
RR
PP
PBut
But
But
P
But
Cl3CCCl3
108
81%
104
105
R = H, SiMe3
88%
106, M = Zr, R = H107, M = Hf, R = H, SiMe3
Scheme 22
172 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
<1997JOM215>. [2+2+2]-Cycloaddition reaction of 116 with numerous alkynes under mildconditions afforded cycloadducts 123 in high yields (Scheme 25) <1997JOM215, 1999S1363>.
The treatment of 1-stannyl-3,5-di-t-butyl-1,2,4-triphospholes 124, which could be obtainedfrom Na[3,5-di-t-butyl-1,2,4-triphospholyl] 125 and R3SnCl, with t-butylphosphaalkyne afforded126 in 80% yield (Scheme 26) <1999MI3143>.
CH2Cl2
Et2O
0 °C, 0.5 h
THF–40 °Cthen rt
C PBut AlCl3P
PPBut
ButAl
But
Cl ClCl
P P
P
PBut
But
But
But
PP
P
PBut
But
But
But
P P
P ButButBut
PP
P ButBut
But+
C PButEt2O
R1
P P
P
R2
But
But
But
R1
PP P
PP
But
But But
ButP
PP
But
ButP
But
P
P
P
But
But
SnMe3
CrCl3(THF) 3 +
+
37%
115
+
118 119
10 min96%
116
118
116 + R2
120
22%–78 °Cthen rt
121
116 117
122
123
31%
DMSO
DMSO
R1 = H, R2
= CO2Me, 71%R1
= R2 = CO2Me, 82%
R1 = R2
= H, 85%R1
= H, R2 = Ph, 78%
R1 = R2
= Me, 88%R1
= R2 = Ph, 85%
R1 = R2
= SiMe3, 80%R1
= Ph, R2 = SiMe3, 70%
+
–
Scheme 25
PP
PBut
But
[Na(THF)x]
PP
P SnR3
But
But
C PBut
SnR3Cl
PP
PBut
But
PR3Sn
CBut
PP P
But
But
But
P
PSnR3But
124
–30 °C
[4+2]-cycloaddition
[2+2+2]-cycloaddition
125
126
R = Ph
R = Me, 98%R = Ph, 87%R = Bun, 90%
70 °C, 12 h
P
Scheme 26
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 173
The co-condensation of electron beam generated titanium atoms with an excess of t-butylphospha-acetylene afforded the hexaphosphatitanocene complex 127. The complex 128was formed as a result ofan unusual [2+2]-cycloaddition with a P¼C bond of one of 127 (Scheme 27) <1999CC1731>.
The Lewis base adducts of imidovanadium(V) compound 129 underwent chemoselectivecyclooligomerizatiom reactions with the phosphaalkynes to afford the corresponding azatetrapho-sphaquadriccyclanes 130 (Scheme 28) <2001ZN(B)951>.
PPPBut
But
P PP But
But
Ti TiP P
P ButBut
P
PP
P
But
But
ButC PBut
127
128
+
Scheme 27
TolueneO
VO
NCl
Cl
Me
Me
R1C PR2
PP P
PR2
R2
NR1
129
+
130R1
= But, 1-Ad
R2 = But, Pent, 1-Ad,
1-Me-Cp, 1-Me-Cy
Scheme 28
Et3N
Toluene
25–70 °C
Et3PToluene 150 °C, 4 days
135134
= 113
C PR1 Sex
C P R2 = But, Pent, 1-Ad,R2
P Se
PR1
R1 C PR2P
P
P
R2
R1Se
R1
PP
P
R2
R1Se
R1
PR2
PP
P
R2
R1Se
R1P
R2
P
P
P
But
But
But
P
But
P P
But
But
P
PBut
But
P
P
P
PBut
But
ButBut
+
15–89%R1 = But, Pent, 1-Ad,
1-Me-Cp, Mes
131
+
132 133
[2 + 2 +2]
134+
25 °C, 14 days
135
[4 + 2]
82% R1 = R2
= But
Scheme 29
174 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
The reaction of the selenodiphospholes 131, which could be obtained from the treatment ofphosphaalkynes with an excess of elemental selenium in toluene in the presence of an equi-molar of Et3N, with phosphaalkynes led to the formation of a pair of regioisomers 132 and133. The removal of the selenium from the cage afforded a mixture of the tetraphosphabis-prismane 135, and the valance isomeric tetraphosphasemibullvalane 134 in a ratio of 11:3(Scheme 29) <2001HAC406>. 134 undergoes a slow and thermal isomerization leading to thebisprismane 135.
Triphosphabicyclo[1.1.1]pentane 138 was obtained in 36% yield from the reaction of phos-phavinyl Grignard reagent 136 with PCl3 in a 3:1 stoichiometry. This is presumably formedvia the bisphosphavinyl phosphorus intermediate 137, which undergoes facile phosphavinylcoupling reaction to give the bicyclic product 138 <2002MI1209>. The analogous reaction of136 with PCl3 in 1:1 stoichiometry afforded the bicyclic product 139 (Scheme 30)<2002MI1209>.
6.05.1.3 Functions Bearing Three Arsenic Atoms
There are only two reports related to this functional group since 1993. The reaction of arsaalkene141 with the lithium salt of tri(trimethylsilyl)phosphine 142 in the presence of CoCl2 gavetetraarsanecubane 140a (M¼As) in 35% yield, which on reaction with Fe2(CO)9 in THFafforded 140b (M¼As+-Fe(CO)4) in 46% yield <1993AG86, 1993AG(E)83>. The arsacubane140a reacts at room temperature with ethyl triflate to give the As-ethylated arsonium salt 140c. Asimilar reaction of 140a with benzyl triflate, generated in situ via PhCH2Cl/AgOTf, gave 140d, theAs-benzylated salt of 140a. Low-temperature protonation of 140a with FSO3H/SO2 produces amixture of arsonium ions 140e, resulting from mono- and diprotonation (Scheme 31)<1994HAC503>.
P
P P
But
ClBut
PCl3Et2O15%
PCBut
MgCl
OEt
Et
PCl3Et2O
P PP
Cl
ButBut
P
P P
Cl
ButCl
ButP
136
137 138
36%
139
1/3 equiv.
1 equiv.
Scheme 30
AsBut
OTMSTMS
(TMS)2PLiAsBut CoCl2
As
MAs
AsBut
ButBut
But 140a, M = As
140b, M = As+–Fe(CO)4
140c, M = As+ –Et
140d, M = As+–CH2Ph
140e, M = As+HFSO3
141
140
142
–
Scheme 31
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 175
6.05.1.4 Functions Bearing Group 15 Elements
6.05.1.4.1 Functions bearing two nitrogen atoms and phosphorus atom
N-benzoyl- and N-methoxycarbonyltrifluoroacetamidophosphonates 145, which could be preparedfrom the reactions of imidoyl chlorides 143 with trialkylphosphites 144, reacted with dimethylcyana-mide 146 in a [4+2]-cycloaddition to give 147 in 48–88% yields (Scheme 32) <2002HAC22>.
When 4,5-dichloro-1,3-dimesitylimidazol-2-ylidene 148 was allowed to react with phosphoruspentafluoride in toluene, 1,3-dimesityl-4,5-dichloroimidazolium-2-pentafluorophosphate 149 wasobtained in 58% yield (Scheme 33) <2000M251>.
6.05.1.4.2 Functions bearing two nitrogen atoms and one arsenic atom
The reaction of the 4,5-dichloro-1,3-dimesitylimidazol-2-ylidene 148 with arsenic pentafluoride in1,3-bis(trifluoromethyl)benzene furnished the 1,3-dimesityl-4,5-dichloroimidazolium-2-pentafluoro-arsenate 150 in 65% yield (Scheme 34) <2000M251>.
N
N
Cl
Cl
Mes
MesF
As FF
FF
1,3-(CF3)2C6H4N
N
Cl
Cl
Mes
As
MesF
FF
F
F
Mes = 1-(2,4,6-mesityl)
+–198 °C
65%
150148
+
–
Scheme 34
P N
CF3
R2
O
OR1O
R1OC NN
Me
Me
N
O
N
F3C P
R2NMe
Me
O OR1
OR1
Cl N
CF3
R2
OPR1O OR1
OR1
+
143
146147
Reflux, 6 h
44–88%
+
5–10 °C3 h
144
145
Et2O, rt, 2 days
R2 = Ph
R2 = Ph, R1
= Me, Et, Prn, Pri
R2 = OMe, R1
= Pri
Scheme 32
N
N
Cl
Cl
Mes
MesFP FF
FF
Toluene N
N
Cl
Cl
Mes
P
MesF
FF
F
F
Mes = 1-(2,4,6-mesityl)
+–198 °C58%
148 149
+
–
Scheme 33
176 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
6.05.1.4.3 Functions bearing two nitrogen atoms and one antimony atom
The reaction of the 4,5-dichloro-1,3-dimesitylimidazol-2-ylidene 148 with antimony pentafluoridein 1,3-bis(trifluoromethyl)benzene furnished the 1,3-dimesityl-4,5-dichloroimidazolium-2-penta-fluoroantimonate 151 in 75% yield (Scheme 35) <2000M251>.
6.05.1.4.4 Functions bearing two phosphorus atoms and one nitrogen atom
The reaction of imidoyl chloride 153, which can be obtained from 152 and PCl5, with diphenylphosphite 154 in the presence of triethylamine gave a mixture of 155 and tetraphenyl 2-fluoro-1-trichloroacetamido-1,1-ethylidenebis-phosphonate 156 in 35% yield (Scheme 36) <2002JFC107>.
G. Olive and co-workers prepared the tetraethyl(pyrrolidine-2,2-diyl)bisphosphonate 158 fromthe reaction of pyrrolidine 157, triethylphosphite, and phosphorus oxychloride in 58% yield(Scheme 37) <1998JOC9095, 2001MI275>.
1-Arylidineamino-1,1-diphosphonoethanes 161 were obtained by Shmarov and co-workersfrom the reaction of aromatic aldehydes 160 with tetrasodium salt of 1-aminoethane-1,1-dipho-sphonic acid 159 in 25–60% yields (Scheme 38) <2000JGU521>.
The reaction of triethyl phosphite with the various types of Vilsmeier reagents 162 preparedfrom the N,N-disubstituted formamides, acetylamides, benzoylamides, phenylacetamides, andphosphorus oxychloride afforded the tetraethyldialkylaminomethylenediphosphanates 163 in30–78% yields. The carbanion 164, generated from 163 by deprotonation with NaH, reactedwith benzyl chloride in THF to give the C-benzylated bis-phosphanate 165 in 32% yield (Scheme 39)<1999HAC271>.
+NH
OEtO P
OEt
OEt
OPCl ClCl
NH
P
P
O
O
OEtOEt
OEtOEt+
–8 °C1 h
158
58%
157
Scheme 37
N
N
Cl
Cl
Mes
MesF
Sb FF
FF
1,3-(CF3)2C6H4N
N
Cl
Cl
Mes
Sb
MesF
FF
F
F
Mes = 1-(2,4,6-mesityl)
+77%
148 151
+
–
Scheme 35
P NH
CCl3
O
OPhO
PhO
F
Cl N CCl3
OF
PPhO OPhH
O
NH
CCl3
OOF
PCl5
NH
F
CCl3
OP
P
O
OPhO
OPh
OPhPhO
+
155
154
153
Et3NEt2O
1 h
Refluxhexane6 h
152156
35%
Scheme 36
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 177
The Wittig rearrangement of the ammonium ylides 169 derived from N-allylic ammonium salts168, prepared by quaternization of the tetraethyldimethylaminomethylene-bis-phosphanate 166,<1968AG(E)391, 1976JPR116, 1982SC415, 1999HAC271> with various allylic halides 167resulted in the formation of tetraethyl bisphosphanates 170 in 35–85% yields (Scheme 40)<1999HAC281>.
P
NP Me
Me
O
OEtO
OEt
EtOOEt
R3
R2
R1
H BF4
NaH THFrt 2 h
P
NP Me
Me
O
OEtO
OEt
EtOOEt
R3
R2
R1
PNH
PMe
Me
O
OEtO OEt
EtO OEt
X R3
R2
R1
PN
PMeMe
O
OOEtEtO
OEtEtOR1
R2
R3
R1 = R2
= R3 = H
R1 = R2
= H, R3 = Me
R1 = Me, R2
= R3 = H
R1 = R2
= H, R3 = Ph
R1 = H, R2
= R3 = Me
+MeCN, AgBF4
reflux, 3–5 h
X=Cl, Br, I
[2,3]-Wittig rearrang.
35– 85%
167168
169170
166
–+
+
–
Scheme 40
OP OEtH
N
OR2
R3
R1OPCl ClCl
CH2Cl2P
NR1
PR3R2
O
OEtO OEt
EtO OEt
PN
PMeMe
O
OEtO OEt
EtO OEt
PhCH2Cl
THF
THF NaH
PNPhH2C
PMeMe
O
OEtO OEt
EtO OEtNa+ –
163
162
164
2EtO + +
30–78%
10 h
R1 = H
R2 = R3
= Me
32%
165
R1 = H, Me, Ph, CH2Ph
R2 = Me, Et, Pr
R3 = Me, Et, Pr, Ph
Scheme 39
H2NP
PMe
O
O
OHHO
OHHO
H
O
R1
R2
R3
N
R1
PMe
P
OHO OH
OHO OH
R2
R3159
+Water–EtOH
161
25–60%
160b, R1 = H, R2
= OH, R3 = NO2
160a, R2 = R3
= H, R1 = OH, Et2N, NO2
Scheme 38
178 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
[4+1]-Cycloaddition reaction of heterodienes 171 with triethyl phosphite gave the 5-phenyl-3-trifluoromethyl-2,3-dihydro-2�5-[1,4,2]oxazaphosphol-3-yl)phosphonic acid diethyl ester deriva-tives 172 (Scheme 41) <1995ZOB948>.
Beckmann rearrangement of oximes 173, in the presence of phosphorus nucleophiles, e.g., di-or triethyl phosphites, afforded the corresponding aminomethylene gem-diphosphanates 174 inmoderate yields (30–60%). The method is applicable to the synthesis of conformationallyrestricted analogs. The diphosphanate 174 (R1=Ph, R2=Me) was converted to diphosphonicacid 175 with TMSBr in CH2Cl2 in 59% yield (Scheme 42) <1994JOC7562>.
Nurgent and co-workers prepared the pyrazoline bis-phosphonates 179 and 180 from the reaction ofvinylidenephosphonic acid tetraethyl ester, 177, which was obtained from the tetraethylmethylenebis-phosphonate 176 and formaldehyde, with diazomethane, diazoacetate 178 (R=OEt), and diazoketones178 (R=Ph, Et, etc.) in ether at room temperature in 30–92% yields (Scheme 43)<1993JMC134>.
R1 R2
NOR
N CR1 R2 R1
R1
N PO
EtO OEt
EtO POEt
OEtEtO P
O
HOEt
CH2Cl2, POCl3
HN
R2
P
P
R1
OEt
OOEt
OOEt
OEt
HN
Me
P
P
Ph
OH
OOH
OOH
OH
TMSBr, CH2Cl2
R = H, Ms
173
R1 = R2
= –(CH4)–
R1 = R2
= –(CH5)–
R1 = Ph, R2
= Me
R1 = Ph, R2
= Et
R1 = 4-MeO–C6H4, R2 = Me
Beckmann
rearrangement
phosphorusnucleophiles (Pnu) =
30–60%
,Pnu
Pnu
174
R1 = Ph R2
= Me
25 °C, 12 h
17559%
+
Scheme 42
EtOP P
OEt
O
OEt
O
OEt
O
HH NHEt2
EtO P P OEtO
EtO
O
OEtCH2
+
N N
O
R
P
H
PO
O
EtO
EtO
OEtEtO
Et2O
N N
P
H
PO
O
EtO
EtO
OEtEtO
O
RN2CH
Et2O
p-TSA, MeOH
176 177
CH2N2,0 °Crt, 18 h
R = OEt, Ph, Et, But, 2-F-C6H4, 3-F-C6H4,
2-Me-C6H4, 3-Me-C6H4, 4-Me-C6H4
32178
179180
Scheme 43
OEtPEtOOEt
CCl4
Ph N
O CF3
Cl O P
NPhPCF3
O OEtOEt
R1
R2R2
+ 84%
R1 = F, Cl, EtO, PhO
R2 = EtO, PhO171 172
Scheme 41
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 179
6.05.1.4.5 Functions bearing two phosphorus atoms and one arsenic atom
Arsadiphosphabicyclo[1.1.1]pentane 182 was obtained in 41% yield from the reaction of phos-phavinyl Grignard reagent 136 with AsCl3. This is presumably formed via the bisphosphavinylphosphorus intermediate 181, which undergoes facile phosphavinyl coupling reaction to give thebicyclic product 182 (Scheme 44) <2002MI1209>.
6.05.1.4.6 Functions bearing two phosphorus atoms and one antimony atom
Two equivalents of the diphosphastibolyl ring anion 183 reacted with FeCl3 to produce anantimony containing cage compound 184 via an oxidative coupling mechanism (Scheme 37)The mechanism for the formation of 184 presumably involves an initial coupling reaction togive the intermediate 185, which then undergoes a [4+2]-cycloaddition reaction affording 184<1997JCS(D)4321, 1997CC305>. The compound 184 was also obtained from the reaction of 183with PbCl2 in 1,2-DME at �45 �C (Scheme 45) <1999JCS(D)4057>.
The reaction of 2 equiv. of 186, which could be prepared from the reaction of 188 and 189, withSiMeCl2 afforded hexahetero-cage compound 187 in moderate yield (41%) (Scheme 46)<2001JOM61>.
Sb PP
But
But
SbP
P But
But
FeCl31,2-DME18 h
[4 + 2]-cycloadditionP
P Sb
ButBut
SbP
PBut
PP
But
But
ButSb
183184
65%
185
Scheme 45
1,2-DME
–78 °C rt
–78 °C then rt
13%
P
P SbH
But But P
P SbH
But
But
K
K
186
(DME)
(DME)
SiMe3
SbMe3Si
SiMe3
SbMe3Si
Me3SiK
P COSiMe3
ButMe3Si+SiP
P
MeMe
ButBut
SbP
P But
But
+ KOBut
187
188
189 41%
188
–78 °C then rt
SiMeCl2THF
Scheme 46
P
P As
But
ClBut
PCBut
MgCl
OEt
EtAsCl3
Et2O
P AsP
Cl
ButBut
136 181 18241%
Scheme 44
180 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
6.05.1.4.7 Functions bearing two antimony atoms and one phosphorus atom
The reaction of phosphavinyl Grignard reagent 136 with SbCl3 led to an unusual heterocycliccompound 190, which quantitatively decomposes in solution to yield the known 1,2-dihydro-1,2-diphosphete 192. Although no intermediate was observed in this reaction, it seems likely that thephosphaalkene 191 initially forms (Scheme 47) <2002MI1209>.
6.05.2 FUNCTIONS CONTAINING TWOGROUP 15 ELEMENTS ANDONE GROUP13 OR 14 ELEMENTS
6.05.2.1 Functions Containing Two Group 15 Elements and One Group 13 Elements
6.05.2.1.1 Functions bearing two nitrogen atoms and one boron atom
Stable imidazol-2-ylidene-borane adducts 194 were obtained from the reaction of imidazol-2-ylidene 193 with Me2S�BH3 or Et2O�BF3 (R1=Me and R2=Me, Et, i-Pr) (Scheme 48) and(R1=H, Cl and R2=Mes) (Scheme 48) <2000M251>.
The silylation of lithium 3,5-dimethyl-1-(dimethylamino)boratabenzene 195 <1999OM5496>with chlorotrimethylsilane afforded 196 in 86% yield, which was then treated with BCl3 to givethe highly reactive chloro-compound 197. When a toluene solution of imidazol-2-ylidene wasadded to a solution of 197 at room temperature, the adduct 198 formed immediately in high yield(80%) (Scheme 49) <2000OM3751>.
The reaction of (E)-2-chlorodimethylstannyl-3-diethylboryl-2-pentene 199 <1986ZNB890>,which could be obtained via 1,1-organoboration of 1-alkynyl compounds 202, with the C-lithiatedimidazoles gave a mixture of 200 and 201, which are present in the beginning as a 1:1 mixture(Scheme 50) <1995JOM197>.
The borolylimidazolium salts 205 were prepared from the reactions of the appropriate1,3-dialkyl-4,5-dimethylimidazol-2-ylidenes with 2-bromo-2,3-dihydro-1H-1,3,2-diazaboroles 204,which were synthesized by cyclocondensation reaction of the corresponding dilithiation of com-pounds 203 with BBr3 in hexane (Scheme 51) <1997CB705>.
N
N
R2R1
R1 B
R2 X
X
X
N
N
R2R1
R1
R2
MeS
MeBH
HH
EtO
EtBF
FF
THFor+
+ –
+ –
+ –
X = H, F
194193
R1 = Me, R2
= Me, Et, Pri
R1 = H, R2
= Mes
R1 = Cl, R2
= Mes
or Et2O
Mes = 2,4,6-mesityl
Scheme 48
PSb
But
Cl ClEt2O
PMg
But
Cl OEt
Et ClSbClCl
+ SbP
PBut
Cl
ClSb
ButCl
Cl
P P
But But
136190
191
66%Solution
192
Scheme 47
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 181
Treatment of 1,4,5-trimethylimidazole with triethylborane at 0 �C led to 3-(triethylborane)-1,4,5-trimethylimidazole 206 in quantitative yield. The treatment of 206 with n-BuLi was expected to yield acarbene 207, surprisingly the rearranged compound lithium triethyl(1,4,5-trimethylimidazolyl)borate208 was obtained in 77% yield (Scheme 52) <1998MI843>. Methylation of 208 with MeI was carriedout in THF at �30 �C affording 209 in 69% yield. The reaction of 1,4,5-trimethylimidazole withBH3THF at 0 �C afforded the air-sensitive compound 3-borane-1,4,5-trimethylimidazole 210, whichwas deprotonated with n-BuLi to give 3-borane-1,4,5-trimethylimidazol-2-ylidene 211. The reaction of211 with chlorobis(dimethylamino)borane 212a, 2-bromo-1,3-di(t-butyl)-1,3,2-diazaboroline 212b,and triethylborane 212c led to 3-borane-2-[bis(dimethylamino)boryl]-1,4,5-trimethylimidazoline 213a
R2 N
N R2R1
R1 BrBBr
Br
+N
BN
R1R1
R2 R2
Br
N
N
Me
Me
R3
R3
NB
N
N
N
R3
R2
R2
R3
Me
Me
R1
R1
Br–
203
R1 = H, R2
= But
R1 = H, R2
= 2,6-Me2-C6H3
R1 = Me, R2
= Pent
Hexane
204
R3 = Me, Pri
205
+
Scheme 51
N
NMe
Me
Li+Me
MeB
NSn
NMe
Et
Et
EtMeMe
Sn B
Et
EtEt
ClMeMe
Me
MeB
NSn
NMe
Et
Et
EtMe
Sn MeCl
MeMe
EtBEtEt
202
200199
+
201
+–
+
–
+–
Scheme 50
BN
MeMe
MeMe
+Li+–
THF2 h, rt B
N
MeMe
MeMe
SiMe3 B
MeMe
SiMe3
Cl
Toluene83%
MeSiMeMe
ClBCl3
N
NMe
Me
Me
Me
N
NMe
Me
Me
Me
B
Me
Me
195 196197
91%86%
198
+
–
+ –
Scheme 49
182 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
in 72% yield <1998MI843>, 2-(1-borane-3,4,5,trimethylimidazoloyl)-1,3-di(t-butyl)-1,3,2-diazaboro-line 213b in 32% yield <1999MI789>, and 3-borane-1,4,5-trimethyl-2-(triethylborane)imidazoline213c in 96% yield, respectively (Scheme 52) <1999MI789>.
Martinez and co-workers prepared the 1,5-dimethyl-4,4,8,8-tetrahydroimidazaboles 215a(Scheme 53) <1994CB343> and 1,5-dibenzyl-4,4,8,8-tetrahydroimidazaboles 215b (Scheme 53)<1998MI1547> from N-methylimidazole-N-borane 214a and N-benzylimidazole-N-borane 214b.
The treatment of 1-alkynyl(chloro)dimethylsilane 216 with tetraethyldiborane or 9-borabicy-clo[3.3.1]nonane dimer, (9-BBN)2, afforded the (Z)-1-chloro-dimethylsilyl-1-diethylboryl-alkenes217 <1999JOM98> and (Z)-1-chloro(dimethyl)silyl-1-(9-borabicyclo[3.3.1]non-9-yl)-3,3-dimethyl-but-1-ene 218 <2000JOM45>, respectively, which were reacted with 2-lithio-1-methylimidazole to
0 °C, 2 htoluene
N
N
Me
Me
Me
B EtEt
EtLi+–
N
N
Me
Me
MeB
EtEt
Et
Me
HBH
HTHF
NB Cl
N
MeMe
MeMe
+
N
N
Me
Me
MeB
B
N
NMe
Me
Me Me
H
H
H
N
N
Me
Me
MeB
BH
HH
N
N
But
But
N
N
Me
Me
Me
EtBEt
Et
N
N
Me
Me
Me
BEt
Et
EtN
N
Me
Me
Me
BEt
Et
Et
BunLi
X
N
N
Me
Me
Me
BH
H
H
BunLi N
N
Me
Me
Me
BH
H
HLi+–
N
NB
But
But
Br
206
207
208
209210
211
99% –78 °C
77%
MeI, THF
–30 °C, 1 h69%
–78 °C
212a213a 212b
211
213b
211
+
–
–
+
–+
–
+
–
+
–
N
N
Me
Me
MeB
BH
H
H
EtEt
Et
EtBEt
Et
212c
213c
211
+
–
Scheme 52
N
BN
B
N
N
R
RH H
H H
N
NR
BH
H
H
I2,270 °C
214a R = Me214b R = CH2Ph
32%
215a R = Me215b R = CH2Ph
+
–
+
+–
–
Scheme 53
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 183
give 219–222. The treatment of 1 equiv. of B(C6F5)3 223 with 2-lithio-1-methylimidazole yields 224 in63% yield (Scheme 54) <2002MI2015>.
6.05.2.1.2 Functions bearing two nitrogen atoms and one gallium atom
The gallium compound 227 was obtained from the reaction of complex 226 <1963IC1039>,which was prepared from lithium gallium hydride and trimethylammonium chloride, with imida-zol-2-ylidene in 40% yield (Scheme 55) <1998JCS(D)3249>. The treatment of 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene with an equimolar amount of LiGaH4 in Et2O afforded thegallium complex 228 in 89% yield (Scheme 55) <2000OM4852>. The treatment of the potentiallychelating reagent bis-carbene 1,2-ethylene-3,30-di-t-butyl-diimidazol-2,20-diylidene 225 withGaH3NMe3 in a 1:1 or 1:2 stoichiometry led to the 2:1 adduct 229, which is moderately thermallystable compound (Scheme 55) <2002JCS(D)1992>.
The unusual reaction of 230 with 1,3,4,5-tetramethylimidazol-2-ylidene in toluene gave complex233 in 54% yield (Scheme 56) <2002JOM487>. A possible mechanism for the formation of 233involves the initial displacement of a [C5H5]
� and formation of an unstable adduct of thedecamethylgallocenium cation 231, which undergoes reaction with the [C5H5]
� counter ion viahydride transfer to form tetramethylfulvane 232 and 233.
6.05.2.1.3 Functions bearing two nitrogen atoms and one indium atom
The reaction of imidazole-2-ylidene with InX3 (X=Cl, Br) yielded 1:1 234 or 1:2 235 complexesdepending on the stoichiometry employed (Scheme 57) <1997JCS(D)4313>. Treatment to anethereal solution of InH3NMe3, generated in situ from LiInH4 with 2 equiv. of imidazol-2-ylideneat �30 �C led to a moderate yield (42%) of 236, which is an extremely air sensitive material(Scheme 57) <1998CC869, 1998JCS(D)3249>. The treatment of LiInH4 with 2 equiv. of imida-zol-2-ylidenes also gave 236 in 38% yield.
N
NMe
Li
N
NMe
LiEt2BH
But
H B
Si
EtEt
Me
Me
Cl
N
NMe
Li
But SiMe
ClMe
But
H B
SiMe
Me
Cl
F
F F
F
F F
F
FF
FF
F
F F F
B
9-BBN
SiN
B
N
Me
MeBut
H
Et
Et
Me
SiN
B
N
Me
MeBut
H
Me
LiB
F
F
FF
F F
F
F
F
FF
F
F F F
N
NMe
Si
NB
N
Me
MeBut
H
Et
Et
Me
Si
NB
N
Me
MeBut
H
Me
++–
+
63%
217
218
219, 80%
220, 93%
221, 20%
222, 7%
223 224
216
+
–
+ –+ –
+–
Scheme 54
184 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
Treatment of an ethereal solution of either LiInH4 or InH3NMe3 with 1 equiv. of the 1,3-dimesitylimidazol-2-ylidene 237 at �78 �C resulted in the formation of indium trihydride complex238 in high yield (Scheme 58) <2000OM4852>. Compound 238 displays a remarkable thermalstability. In solution the products of decomposition depends on the solvent used. In toluenedecomposition results in liberation of the free carbene and deposition of indium metal, in CH2Cl2,chloride abstraction occurs from the solvent to yield 240. The reaction of InH2ClNMe3 with anequimolar amount of 237 afforded 239 in 65% yield. The reaction of 0.5 or 1 equiv. of the 1,3-dimesitylimidazol-2-ylidene 237 with InBr in toluene at 25 �C led to the deposition of indium metal
Ga
MeMe
Me
MeMe
Me
Me Me
Me
MeMe
Me
Me
Me
Me N
NMe
MeMe
Me
Ga
N
N
Me Me
Me
MeMe
Me
Me Me
Me
MeMe
Me
Me
MeH
+
MeMe
Me Me
Ga
N
N
Me Me
Me
MeMe
Me
Me Me
Me
MeMe
Me
Me
MeMe
MeMe
Me
Me
+Toluene
–78 °C
rt54%
230
231
232
233
+ –
+
–
Scheme 56
H GaH
HH
LiMeNMe HMe
+ ClEt2O
–30 °C3 h
H GaH
NH
Me
MeMe
N
NMe
Me
Pri
Pri
Pri
Pri
Et2O
N
NMe
Me
Ga HH
H
N
N
Mes
MesEt2O
N
N
Mes
Mes
Ga HH
H
N
NBut
N
NBut
Et2O
NNButN N But
Ga
Ga
H
H
H
H
H
H
226
–78 °C,
227
40%
Mes = 2,4,6-mesityl
–78 °C
rt89%
228
229
–50 °C59%
225
+– + – +–
+ –
+
–
+
–
+ –
Scheme 55
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 185
and formation of the thermally robust carbene–indium complex 241 in 54% yield (Scheme 58)<2002CC1196>. The treatment of 1,3-dimesitylimidazol-2-yliden 237 with InBr3 and Et2O withcarefully resublimed InBr3 afforded 1:1 adduct 242 in 88% yield (Scheme 58) <2002JOM203>.
Treatment of bis-carbene, 1,2-ethylene-3,30-di-t-butyldiimidazol-2,20-diylidene 225, with LiInH4
or InH3NMe3 in a 1:1 or 1:2 stoichiometry led to good yields of the indium-rich 2:1 adduct 243.In contrast, the 1:1 or 1:2 reaction of 243 with InBr3 yielded the 1:1 adduct 244 in 41% yield(Scheme 59) <2002JCS(D)1992>.
N
NMes
Mes
N
NMes
Mes
InH
HH
LiInH4
InH3NMe3
InH2ClNM3
N
NMes
Mes
InCl
ClCl
N
NMes
Mes
InH
HCl
CH2Cl2
InBr
N
NMes
Mes
InBr
BrInBr
Br N
NMes
Mes
InBr3
Et2O
N
NMes
Mes
InBr
BrBr
86%
54%
65% Et2O–50 °C
–50 °C, then rt67%
toluene
25 °C54%
2 h88%
237 238
239 240
241
242
+ +––
+
–
+
–
+
–
+
–
Scheme 58
N
NMe
Me
InX
XX
THF
N
NMe
MePri
Pri
Pri
Pri
Pri
Pri Pri
Pri
Pri
Pri
In XX
X
N
NMe
Me
InX
XXN
NMe
MeInX
XX
N
NMe
Me
In HH
H
HInH
H NMe
MeMe
Et2O
HInHH
H
THF
X = Cl 74%X = Br 43%
X = Cl, 38%X = Br, 69%
1:1
1:2
–30 °C2 h, 42%
–30 °C5 h, 38%
20 °C3 h
20 °C3 h
234
235
236
+ –
+ +
+ –
+–
–
Scheme 57
186 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
6.05.2.1.4 Functions bearing two nitrogen atoms and one thallium atom
Treatment of bis-carbene, 1,2-ethylene-3,30-di-t-butyl-diimidazol-2,20-diylidene 225, with 2 equiv.of TlCl3 in THF yielded the 1:1 adduct 245 in 92% yield (Scheme 60) <2002JCS(D)1992>.
6.05.2.1.5 Functions two phosphorus atoms and one gallium atom
Phosphaalkyne (R= t-Bu) underwent spirocyclotrimerization with GaCl3 to form the betainestructure 246 in high yield (95%) (Scheme 61) <1996CB489>. When triethylgallium was reactedwith 3 equiv. of phosphaalkyne (R= t-Bu and 1-Ad) in Et2O at room temperature yielded 247in moderate yield (43–49%) (Scheme 61) <1998MI1597>. Exocyclic triethylgallium unit iscoordinated at a phosphorus atom of the polycyclic system.
R = But R = 1-Ad
49%43%
C PR
ClGaCl
ClCH2Cl2
P
PR
R
GaCl
Cl
Cl
EtGaEt
EtEt2O
P
P Ga
R
EtP
GaEt
R
Et
EtEt
Et
R
24695%R = But
48 h, rt247
+–
++
–
–
Scheme 61
H InH
HH
Li+
++
Et2O, –50 °C, 48%
Et2O, –78 °C, 58%
H InH
NH
Me
MeMe
NNButN N But NNBut
N N But
In
In
H
H
H
H
H
HInBr3
THF
N
N
But
InBr
Br
Br N
N
But
243
2 equiv.
–78 °C then rt41%
244
225
+–
–
+
–
+
–
Scheme 59
ClTlCl
Cl2NNBut
N N ButTHF
N
N
But
TlCl
Cl
Cl N
N
But
–78 °C then rt92%
+
245225
++
Scheme 60
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 187
Lithiation of 248 with 1 equiv. of n-butyllithium in THF gave the monolithium salt of theproduct 249 in 78% yield, which was then reacted with GaCl3 to furnish the compound 250 in68% yield (Scheme 62) <1999JA2939>.
The reaction of 3 equiv. of 136 with gallium(III) chloride in toluene led to the formation ofdiphosphagalliumbicyclo[1.1.1]pentane complex 253 in low yield (15%) (Scheme 63)<2001JOM109>. The mechanism of this reaction is not determined as the reaction proceedstoo rapidly to observe any intermediate by 31P-NMR spectroscopy. However, it is believed thatthe gallium chloride initially reacts with 2 equiv. of 136 to give the intermediate 251, which thenundergoes intramolecular phosphavinyl coupling reaction to afford 252, which reacts with a thirdequivalent of 136 to yield 253.
6.05.2.1.6 Functions bearing two phosphorus atoms and one indium atom
The reaction of 3 equiv. of 136 with indium(III) chloride in toluene led to the formation ofdiphosphaindiumbicyclo[1.1.1]pentane complex 256 in (42%) yield (Scheme 64) <2001JOM109>.The mechanism of this reaction is not determined as the reaction proceeds too rapidly toobserve any intermediate by 31P-NMR spectroscopy. However, it is believed that theindium chloride initially reacts with 2 equiv. of 136 to give the intermediate 254, which then
Bun
THF
LiN PSiMe
Me Ph
Ph PN Si
Me
MeMePh
PhMe
ClGa
Cl Cl
N PSiMe
Me Ph
Ph PN Si
Me
MeMePh
PhMe
N PSiMe
Me Ph
Ph PN Si
MeMe
MePh
Ph
GaCl
Cl
Me
248 249
Benzene
250
78%
68%
+
–
Scheme 62
P
P
Ga
But
But
Cl
PButP
P
Ga
But
But
P
Ga
P
ButCl
But
ClGa
Cl Cl
P
But
MgCl
OEt
Et
Toluene
136
251
15%
253
3 equiv.
252
136
Scheme 63
188 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
undergoes intramolecular phosphavinyl coupling reaction to afford 255, which reacts with a thirdequivalent of 136 to yield 256.
6.05.2.1.7 Functions bearing one phosphorus, one nitrogen, and one boron atom
The reaction of 257 with BF3OEt2 or BH3THF afforded 258, which was then treated with�,�-unsaturated esters to yield pyrazolines 259 (Scheme 65) <1991AG(E)1154>.
6.05.2.2 Functions Containing Two Group 15 Elements and One Group 14 Element
6.05.2.2.1 Functions bearing two nitrogen atoms and one silicon atom
Photolysis of a benzene solution of (1-methyl-2,3,4,5-tetraphenyl-1-silacyclopentadienyl) diazo-methane 260 in an excess of methanol yielded (1-methyl-2,3,4,5-tetraphenyl-1-silacyclopentadi-enyl)diazirine 261 and other side products 262–264 (Scheme 66) <1985OM584>.
6.05.2.2.2 Functions bearing two nitrogen atoms and one germanium atom
Triphenylgermyl-bis(3,5-dimethylpyrazol-1-yl)methane 267 could be prepared by the reaction ofbis(3,5-dimethylpyrazol-1-yl)methyllithium 266, which was generated from 265 and n-BuLi in THF,with triphenylgermanium bromide in moderate yield (48%) (Scheme 67) <2002JOM198>. Thetreatment of 267 with W(CO)5THF prepared in situ afforded complex 268 in 43% yield.
P
P
In
But
But
Cl
PButP
P
In
But
But
P
In
P
ButCl
But
ClIn
Cl Cl
P
But
MgCl
OEt
Et
Toluene
136
254
42%
256
3 equiv.
255
136
Scheme 64
PN
NPri
PriPri
Pri Pri
PriPri
Pri Pri
Pri
Pri
Pri
Cl C N NBF3OEt2
BH3THF
PN
NCl C
NN
BX X
X
OMe
O
R
N N
CO2Me
RB
P
XX
X
NCl
N
257
X = H, F
or
258
R = H, CO2Me
259X = F
+ –
+
–
+
–
Scheme 65
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 189
6.05.2.2.3 Functions bearing two phosphorus atoms and one silicon atom
The reaction of 2 equiv. of t-butylphosphaalkyne with silene 270, which was obtained thermallyfrom the disilacyclobutane 269 by [2+2]-cycloreversion, afforded diphosphatricyclobenzoheptane271 in 75% yield (Scheme 68) <1994JOM41>.
Hydrostannylation of phosphaalkene 272 with tributyltin hydride in pentane or petroleumether gave 1,3-diphosphacyclobutane 273 in low yield (7%) (Scheme 69) <1998HAC453>.
BunLi–78 °C, 1 h
PhGePh BrPh
THF
Li+–
NN N
N
Me
Me
Me
Me
NN N
N
Me
Me
Me
Me
W(CO)5THFNN N
NW CO
COOCOCMe
Me
Me
MeGePh
PhPh
NN N
N
Me
Me
Me
MeGePh
PhPh
265 266
267
48%
43%
268
Scheme 67
∆Si SiSiMe3
SiMe3
Me3SiMe3Si
Me3SiOPh
OSiMe3Ph
SiMe3Si OSiMe3
Me3Si PhC PBut
P But
SiMe3Si
Me3SiMe3SiO
PBut269 270
Toluene
75%
271
Scheme 68
Petroleum ether
20 °C, 1 daysP C
Ph
SiMe3Cl Bu3SnH
HP
PH
Ph
Me3Si
SiMe3
Ph
272
+
7% 273
Scheme 69
hνBenzeneMeOHSi
Ph
Ph
Ph
PhMe CHN2
Si
Ph
Ph
Ph
PhMe
NN
Si
Ph
Ph
Ph
PhEt OMe
+ +SiPh
PhPh
Ph
Me OMeSi
PhPh
Ph
Me OMePh
+
48%19%260
261262 263 264
7% 8%
Scheme 66
190 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
1,3-Diphosphacyclobutane-2,4-diyl 275, which can be obtained from 1,3-diphosphacyclobutane-2,4-diyl 274 by selective Cl/SiMe3 exchange, can be transformed into the protonated form 276 withn-BuLi and subsequent t-BuOH addition. Where 276 is thermally stable, irradiation induced a rapidconversion of 276 into the 1,3-diphosphabicyclo[1.1.0]butane 277, which can be transformed intothe 1,4-diphosphabutadiene 278 in 68% yield by heating 277 (Scheme 70) <1999AG(E)3028>.
The reaction of trimethylsilylphosphaacetylene, which can be prepared from dichloro(trimethyl-silyl)methylphosphane 279 in 70% yield <1991AG(E)196>, with an excess of the buta-1,3-dienes(R=H, Me) produced in a 2:1 stoichiometry the phosphatricyclooctenes 282 in 50–55% yields(Scheme 71) <1999MI363>. The Diels–Alder adduct 280 as well as the product 281 of a phospha-ene reaction are assumed to be formed as intermediates prior to the intramolecular [4+2]-cycloaddition leading to the polycyclic product 282.
The stable bis(amino)silylenes 283 underwent smooth [1+4]-cycloaddition with 2,4,6-tri-t-butyl-1,3,5-triphosphabenzene 284 to furnish 285 in 66% and 80% yields, respectively (Scheme 72)<2002JCS(D)484>.
6.05.2.2.4 Functions bearing two phosphorus atoms and one germanium atom
The compound 287 was prepared in high yield (80%) from the reaction of 286 with 1 equiv. ofGeCl2. The compound 287 was then treated with carbanion 289 to yield 288 in 75% yield(Scheme 73) <1999OM389>.
350 °C
R
R
R = H, Me
[4 + 2]Intramolecular
HP HCl
Cl TMS
C PTMSP
HTMSR
R
C PTMS
P
R
R
TMSH
TMS
P
R
R
P
TMS
TMS
279 280
281
ene reaction
50–55%
282
[4 + 2]rt, 2 h
Scheme 71
Hg(SiMe3)2 BunLi
ButOHP P
Cl
Cl
MesMes P P
Cl
SiMe3
MesMes P P
H
SiMe3
MesMes
P P
H
SiMe3
MesMes∆
P
PH
Me3Si
Mes
Mes
Mes = 2,4,6-But C6H2
274 275
97%
90%
276
277
68%
278
71%
hν3
Scheme 70
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 191
The metallation of bis(iminophosphorano)methane 290 with n-BuLi in THF gave the mono-lithium salt 291, which was then reacted with 0.5 equiv. of GeCl2 to produce bis(germavinylidene)292 in 42% yield (Scheme 74) <2001AG(E)2501>. The reaction of 292 with W(CO)5 and Cr(CO)5in THF afforded 293 in moderate yields (37% and 43%) (Scheme 74) <2003CC248>.
6.05.2.2.5 Functions bearing two phosphorus atoms and one tin atom
Reactions of the tin hydrides with an excess of the phosphaalkynes at room temperature for 2weeks gave the 2-stannyl-substituted 1,2-dihydro-1,3-diphosphetes 294 in 22–74% yields depend-ing on substituents. Reactions of the phosphaalkyne (R=But) with chlorodiorganotin hydridesproceed much less selectively than those with the triorganotin hydrides. In addition to the
HC PPh
PhPPhPh
Li+–
N
Ge
N
SiMe3
SiMe3
Me3Si
Me3Si
Et2O
NGe
SiMe3
SiMe3
Cl
Et2O
NGe
SiMe3
SiMe3
PPPh
Ph
Ph
Ph
286
GeCl2dioxane
287
80%
289
288
75%
Scheme 73
n-BuLiTHF
Et2O, dioxane
1/2 equiv. GeCl2P N
P NPh
Ph
PhPh
SiMe3
SiMe3
P N
P NPh
Ph
PhPh
SiMe3
SiMe3
Li+ – N
P
Ge Ge
PN P
P Ph
Ph
Ph
Ph
N
N
SiMe3
SiMe3Me3Si
Me3Si Ph Ph
PhPh
N
P
Ge
PPh
Ph NSiMe3
Me3Si
PhPh
M(CO)3
M(CO)5
M(CO)5THF
290 291
292
42%
M = W, 37%M = Cr, 43%
293
Scheme 74
BenzeneP P
PBut
But
But
But
P
P P
Si
But
But
[NN]
[NNSi]
283
+66–80%
284
But
But
NSi
NCH2But
CH2But
[NNSi] =N
SiN
and
285
Scheme 72
192 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
1,2-dihydro-1,3-diphosphetes 295 formed as main product with the yield (85%), numerous sideproducts were formed (Scheme 75) <1998MI235>.
6.05.2.2.6 Functions bearing two antimony atoms and one silicon atom
The chloro-bridged polymeric C-centered geminal distibine 298 was obtained in 63% yield by thethermolysis of the doubly bonded intermediate species 297, which could be prepared from 296and SbCl3 (Scheme 76) <1998CC575>.
6.05.2.2.7 Functions bearing one nitrogen atom, one phosphorus atom, and one silicon atom
[1+2]-Cycloaddition reaction of [bis(dicyclohexylamino)phosphino]trimethylsilylcarbene 299 withbenzonitrile in toluene afforded 2-phosphino-2H-azirine 300 in 85% yield (Scheme 77)<1995AG(E)1246, 1997MI1757>.
Toluene
NP
N SiMe3C NPh
NPh
Me3Si
PN
N
299
+85%
300
Scheme 77
THF–78 °C then rt
Et2O
–78 °C
Toluene 50 °C4 h
NSiMe3
Cl
NLi
N
SiMe3
SiMe3
NMe
MeMe
Me
ClSbCl
Cl
N
Sb Sb
NMe3Si
SiMe3
Cl
ClCl
NSiMe3
SiMe3
SbCl
Cl296
+
3 days297
298
63%
Scheme 76
n-Pentane2 weeks
C PR2
n-Pentane2 weeks
C PR2
85%
[2 + 2]-cycloaddition
C PR2 C PR2
R13Sn
H
P
PSnR1
3
R2
R2
C PR2 C PR2
R12ClSn
H
PP
SnClR12
R2
R2
R13SnH +
R2 = t-Bu, t-Pent, 1-AdR1
= n-Bu, Ph294
22–74%[2 + 2]-cycloaddition
R12ClSnH +
R1 = n-Pr, n-Bu
295R2 = But
Scheme 75
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 193
6.05.2.2.8 Functions bearing one phosphorus atom, one antimony atom, and one silicon atom
See compound 187 in Scheme 46 in Section 6.05.1.4.6.
6.05.3 FUNCTIONS CONTAINING ONLY ONE GROUP 15 ELEMENT
6.05.3.1 Functions Bearing One Nitrogen Atom and Two Silicon Atoms
The functionalization of imines 302, which were prepared from the reactions of bis(trimethyl-silyl)methylamine (BSMA) 301 and aldehydes, with electrophilic reagents through the formationof an intermediate 2-azaallylmetallic derivative 303 by hydrogen–metal exchange was carried outby A. Ricci and co-workers (Scheme 78) <1994SL955>. A very good control of the regioselec-tivity occurs in the deprotonation of imino derivatives of 301 followed by quenching withelectrophiles. Functionalization at C-1 or C-3 takes place selectively depending on the nature ofelectrophile and base used (304 and 305).
Bis(trimethylsilyl)methyl-isocyanate 309 and bis(trimethylsilyl)methyl-isothiocyanate 310 wereobtained from the reactions of [[bis(trimethylsilyl)methyl]imino]triphenylphosphorane 308, whichwas prepared from bis(trimethylsilyl)methyl azide 307 generated from bis(trimethylsilyl)methylchloride 306, with PPh3 in 81% and 83% yields, respectively (Scheme 79) <1995JOC6032>. Thesymmetrically substituted bis(trimethylsilyl)methyl carbodiimide 311 could be prepared in 76%yield via a Wittig-type reaction of 308 with 309. The synthesis of the unsymmetrically substitutedcarbodiimide 312 was performed by using two different procedures. The compound 312 wasobtained in a 2.5:1 mixture with the symmetrically substituted N,N0-diphenylcarbodiimide 313from the reaction of 308 with phenyl isocyanate or by the reaction of N-phenyltriphenylpho-sphinimine 314 with 309 in 82% yield (Scheme 79) <1995JOC6032>. [Bis(trimethylsilyl)methyl]-sulfinylamine 315 was prepared by the reaction of BSMA with thionyl chloride in 65% yield.
Mono- and bis(trimethylsilyl)benzyl isothiocyanates 316 and 317 were synthesized vialithiated benzyl isothiocyanates and chlorotrimethylsilane in 88% and 91% yields, respectively(Scheme 80) <1997MI232>.
The reaction of N-BOC-2-trimethylsilylpyrrolidine 318 with chlorotrimethylsilane in the pre-sence of TMEDA afforded a mixture of N-BOC-2,2-bis(trimethylsilyl)pyrrolidine 319 and N-BOC-2,5-bis(trimethylsilyl)pyrrolidine 320 in 71% yield (Scheme 81) <2001MI1061>. The use ofHMPA in place of TMEDA resulted in the formation of completely regioselective product 320 in87% yield (Scheme 81) <2002JA14824>.
The transient silenes 322, which are strongly influenced by reverse Si¼C bond polarization,were formed upon heating of tris(trimethylsilyl)silylamides 321. The silenes were trapped with
Mol. sievebenzene0 °C then rt
THFBase
E+
Me3SiNH2
Me3Si
O
HR+
Me3SiN
Me3Si H
R Me3SiN
Me3Si H
R
Me3SiN
Me3Si H
RM+–
M+ –
Me3SiN
Me3Si H
RE
Me3SiN
Me3Si H
RE
301
R = Ph, Me3Si–CH=CH, Et–CH=CH302
303
+
304 305
R = PhBase = MeLiE+
= MeI63% yield
R = PhBase = MeLiE+
= Me3SiCl60% yield
Scheme 78
194 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
2,3-dimethyl-1,3-butadiene to afford a quantitative yield of only one of the possible diastereo-mers of the functionalized cyclic allyl silanes 323 (Scheme 82) <2002MI1915>.
6.05.3.2 Functions Bearing One Phosphorus Atom and Two Silicon Atoms
The P-metallophosphiranes 325 could be prepared from the reaction of 324 <1986OM593> witharyl isocyanides in moderate yields (56–69%) (Scheme 83) <1993OM4653>.
LDA, Et2O–hexaneN C SPhH2C
N C SPh
Me3SiH
N C SPh
Me3SiSiMe3
316
1 equiv. Me3SiCl
2 equiv. Me3SiCl
88%
91%317
Scheme 80
i. BusLi, Et2O, TMEDA
i. BusLi, Et2O, HMPA
ii. Me3SiCl, 71%
ii. Me3SiCl, 87%
NCOOBut
SiMe3
NCOOBut
SiMe3
Me3Si+
NCOOBut
SiMe3
SiMe3
318
319 320
320
Scheme 81
NaN3 PPh3
THF25 °C 2 h
Benzenereflux3 h
Ph N C O
Me3Si
Me3SiCl
Me3Si
Me3SiN3
Me3Si
Me3SiN PPh3
CO2
CS2
Me3Si
Me3SiN C O
Me3Si
Me3SiN C S
Me3Si
Me3SiN C N PhPh N C O Ph N C N Ph
N PPhPh
PhPh
Et2O25 °C 5 min
81%
83%
+
56% 82%
306 307 308
309
310
Benzenereflux1 h
Me3Si
Me3SiN C N
SiMe3
SiMe3+
76%
308 309
311
308
312 313
314
Et2O
Et3N65%
Me3Si
Me3SiNH2 SOCl2
Me3Si
Me3SiN S O+
315
312:313 = 2.5:1309
Scheme 79
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 195
The reaction ofP-chloro-bis(trimethylsilyl)methylenephosphane 326with diisopropyl(trichlorosilyl)-phosphane 327 afforded 1-bis(trimethyl)methylidene-2,2-diisopropyldiphosphane 328 in 82% yield(Scheme 84) <1998ZAAC1447>. The P¼C double bond in 328 could be protected reversibly by a[2+4]-cycloaddition with cyclopentadiene resulting in the formation of a P-phosphanyl phosphannor-bornene 329, with 2,3-dimethylbutadiene produced the cyclic diphosphane 330, and with selenium gave331 which was then treated with cyclopentadiene to furnish 332.
FeOC
OC
PC
SiMe3
SiMe3
Benzene
20 °C, 2 hFeOCCO
P
N
SiMe3
SiMe3
Ar
N CAr
324
+
325
Ar = Ph, 56%Ar = 2-MeC6H4, 67%Ar = 2,6-(Me)2C6H3, 69%
+ –
Scheme 83
Pri
PriPri
Pri
Me
Me
P P
Me3Si SiMe3
PMe
Me
P
SiMe3
SiMe3
CH2Cl2P
Me3Si
Me3SiCl P
Pri
Pri
Pri
Pri
SiCl3 PMe3Si
Me3SiP
326
+
327 328
82%+ SiCl4
328 328+ +
Pentane20 °C
329
91%74%
330
Pri
Pri
PriPriSe PMe3Si
Me3SiSe P
SeP Se
Me3Si SiMe3
PSe
328 +
331332
70%
Scheme 84
∆benzene
O
Si NR2
R1
TMSTMS
TMSO
Si NR2
R1
TMS
TMS
TMSO
Si NR2
R1
TMS
TMS
TMS
Me Me
Si
MeMe
TMSO
TMS
TMSNR1R2
321 322
R1 = R2
= Ph, 97%
R1 = R2
= Me, 88%
R1 = Me, R2
= Ph, 95%
323
+
– +–
Scheme 82
196 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
The deprotonation of 6-methyl-2-bis(trimethylsilyl)methylpyridine 333 with n-BuLi in Et2O orTHF gave 334, which was then treated with PCl3 at �78 �C in Et2O to give the [6-methyl-2-bis(trimethylsilyl)methylpyridine]-phosphorus dichloride 335 in 66% yield (Scheme 85)<2000JOM213>. The reaction of 335 with LiAlH4 in THF afforded 336 in 42% yield<2000CC1961>. When the reaction was carried out in Et2O, the compound 337 was obtainedand not the expected dihydride species <1998CC547>. As seen in Scheme 85, the choice ofsolvent is crucial.
The LiBr-phosphoranylidine carbenoid 339 was obtained by treatment of dibromo species 338<1999JA5953> with 1 equiv. of n-BuLi at �78 �C. In typical carbanion fashion, 339 reacted withwater to give the bis(methylene)phosphorane 341 (Scheme 86) <2002OM4919>. The reaction ofthe dibromo compound 338 with 2 equiv. of n-BuLi afforded 340, which was then quenched withwater or MeI to furnish the product 342 in 96% yield. The dimethylated bis(methylene)pho-sphorane 342b was not stable and rearranged within days to form vinyl-substituted phosphane343 in 69% yield (Scheme 86) <2002OM4919>.
6.05.3.3 Functions Bearing One Arsenic Atom and Two Silicon Atoms
The deprotonation of 6-methyl-2-bis(trimethylsilyl)methylpyridine 333 with n-BuLi in Et2O orTHF gave 334, which was then treated with AsCl3 at �78 �C in Et2O to give the [6-methyl-2-bis(trimethylsilyl)methylpyridine]-arsenic dichloride 344 in 68% yield (Scheme 87)<2000JOM213>. The reaction of 344 with LiAlH4 in THF afforded 345 in 35% yield. Whenthe reaction was carried out in Et2O, the dihydride species 346 was obtained in 60% yield<2000CC1961>.
6.05.3.4 Functions Bearing One Antimony Atom and Two Silicon Atoms
The monochloride species 347 was obtained from the 2:1 reaction of 296 with SbCl3. Thecompound 347 is not stable and Me3SiCl elimination at room temperature occurs giving 348,
BunLi
THF, 0 °C
PCl3, Et2O
–78 °C, 6 h NSiMe3
SiMe3
Me NSiMe3
SiMe3
MeLi+–
NSiMe3
SiMe3Me
PClCl333 334
335
THF
–78 °C
–78 °C
Et2O
N
Me3SiSiMe3
Me
P H
Al
H
H
AlP
N
Me
Me3SiSiMe3H
NMeP
SiMe3Me3Si
PH
H
Me3Si SiMe3
N Me
335 + LiAlH4 336
337
66%
Scheme 85
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 197
which was then reacted with AlMe3 in THF to afford 349 in 32% yield (Scheme 88)<1997CC1183>, with Et3In in hexane at �78 �C to give 350 in 63% yield <1999OM4247>,and with Me3Ga either in THF–hexane at �78 �C to produce 351 in 73% yield <2000OM1277>or in hexane at room temperature to furnish 352 in 34% yield, which was also prepared bywarming a hexane–toluene solution of 351 to 60 �C for 4 h and allowing it to cool to roomtemperature, followed by refrigeration at 4 �C <2000OM1277>.
The deprotonation of 6-methyl-2-bis(trimethylsilyl)methylpyridine 333 with n-BuLi in Et2O orTHF gave 334, which was then treated with SbCl3 at �78 �C in Et2O to give the [6-methyl-2-bis(trimethylsilyl)methylpyridine]antimony dichloride 353 in 74% yield. When the reaction wasrun in THF at �78 �C, 354 was obtained in 58% yield (Scheme 89) <2000JOM213>.
BunLiTHF, 0 °C
AsCl3, Et2O
–78 °C, 6 h NSiMe3
SiMe3
Me NSiMe3
SiMe3
MeLi+–
NSiMe3
SiMe3Me
AsCl
Cl333 334
344
68%
THF
–78 °C
–78 °C
Et2O
N
Me3SiSiMe3
Me
As H
Al
H
H
AlAs
N
Me
Me3SiSiMe3H
NMe
AsSiMe3
SiMe3
HH
344 + LiAlH4345
346
35%
60%
Scheme 87
R = Me
Pentane4 weeks–25 °C
PBr
BrMes
Me3SiBus P
Br
Mes
Me3SiSiMe3
Li
PMes
Me3SiSiMe3
Li
Li
H2OP
Br
Mes
Me3SiSiMe3
H
PMes
Me3SiSiMe3
R
R
PMes
Me3SiSiMe3
CH2
Me
338
1 equiv. BuLi
2 equiv. BuLi
339
340
341
97%
96%
69%
343
342a R = H342b R = Me
H2O or MeI
Scheme 86
198 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
6.05.3.5 Functions Bearing One Bismuth Atom and Two Silicon Atoms
The treatment of a THF solution of 1-aza-allyllithium salt 355 <1999OM2256> with BiBr3 intoluene afforded the mono(1-aza-allyl)bismuth dibromide 356 in 69% yield, which is notstable in solution, and slowly decomposes even under inert atmosphere (Scheme 90)<2000POL471>.
6.05.3.6 Functions Bearing One Antimony Atom, One Gallium Atom, and One Silicon Atom
See compounds 351 and 352 in Scheme 88 in Section 6.05.3.4.
Et2O
–78 °C
Et3In
Hexane–78 °C
THF–78 °C
NSiMe3
SiMe3N
N
Li
Me
Me
Me
Me
ClSb
ClCl+
NSiMe3
SiMe3
SbCl N
Me3SiSiMe3
NSiMe3
SiMe3
Sb N
Me3Si
N
In
Sb
SiMe3
SiMe3
SiMe3
N
Et
Et
Et
N
GaSi
SiMe3
Me3Si SbMe
N
Me
MeMe
N
Al
Sb
Me3Si SiMe3
SiMe3
N
MeMe
Me
N
Ga
Sb
Me3Si SiMe3
SiMe3
N
MeMe
Me
296 347 348
349
2.5 equiv. AlMe3
350
63%
1.5 equiv. Me3Ga.THF
THF–Hexane–78 °C
73%
+
+
351
+ Hexanert
352
TolueneHexane60 °C4 h
32%348
348
348
348
+
Me3Ga.THF
–
Scheme 88
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 199
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THF–toluene
–78 °C then rt20 hSiMe3
NPh
Me3Si
SiMe3
Li+– BrBiBr
Br Bi
NPh
Me3SiMe3Si
BrBr
SiMe3
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355 356
Scheme 90
BunLiTHF, 0 °C
SbCl3, Et2O
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SbCl3, THF
–78 °C, 6 h
NSiMe3
SiMe3
Me NSiMe3
SiMe3
MeLi+–
NSiMe3
SiMe3Me
SbCl
Cl
SbCl3+
SbCl3+ Sb
ClSb
ClNN
SiMe3
SiMe3
Me
Me
Cl
Cl
333 334
353
74%
58%
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334
334
Scheme 89
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202 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)
Biographical sketch
Alaettin Guven is currently Associate Professor of organic chemistry atChemistry Department at Anadolu University, Eskisehir, Turkey. Hewas born in Eskisehir-Turkey, received a B.Sc. in chemical engineeringin 1976 and M.Sc. in Chemistry in 1987 from Anadolu University. Heobtained a Ph.D. in 1992 under the direction of Dr. R. Alan Jones atUEA in Norwich, England. He held postdoctoral position from 2002 to2003 in the laboratories of Professor Alan R. Katritzky at UFL inGainesville, Florida. His scientific interests are computational chemistry,acidity, conformation, and tautomerism in heterocyclic systems.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 161–203
Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 203
6.06
Functions Containing at Least One
Metalloid (Si, Ge, or B) and No
Halogen, Chalcogen, or Group 15
Elements; Also the Synthesis of
Functions Containing Three Metals
V. D. ROMANENKO and V. L. RUDZEVICH
National Academy of Sciences of Ukraine, Kiev, Ukraine
6.06.1 INTRODUCTION 2056.06.2 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION
(AND NO HALOGEN, CHALCOGEN, OR GROUP 15 ELEMENTS) 2066.06.2.1 Synthesis of Functions Containing Three Metalloids 2066.06.2.1.1 Functions bearing three silicons 2066.06.2.1.2 Functions bearing three borons 2146.06.2.1.3 Functions bearing three germaniums 2206.06.2.1.4 Functions bearing mixed metalloids 221
6.06.2.2 Functions Containing Metalloids and Metals 2266.06.2.2.1 Functions bearing silicon(s) and metal(s) 2266.06.2.2.2 Functions bearing boron(s) and metal(s) 2326.06.2.2.3 Functions bearing germanium(s) and metal(s) 2326.06.2.2.4 Functions bearing mixed metalloid(s) and metal(s) 232
6.06.3 FUNCTIONS CONTAINING THREE METALS 2356.06.3.1 Three Similar Metals 2356.06.3.2 Three Dissimilar Metals 237
6.06.1 INTRODUCTION
This chapter outlines the synthesis and reactions of compounds of the general formula(XmE)n(LkM)3�nCR (R=H or organyl; E=Si, Ge, or B; M=metal; X, L=any substituents;n=0–3) having three heteroatoms (E, M) bonded to the same carbon. Much of the importantpioneering work on these species was carried out in the 1970s and 1980s; COFGT (1995) covers thefield up to 1994 <1995COFGT(6)171>. Use of the tris(trimethylsilyl)methyl (trisyl) group,(TMS)3C, in organometallic chemistry began with the demonstration that this function can beattached to a wide range of elements by simple ligand transfer from the lithium reagent (TMS)3CLi<1970JOM(24)529>. Since that time, numerous studies have shown that organometallic com-pounds containing the bulky ‘‘trisyl’’ group adopt a range of unprecedented structures and are
205
much more chemically and thermally stable than analogous derivatives with smaller alkyl groups.This topic has been summarized in review articles<1996CCR125, 1995JOM(500)89>, both of whichemphasize the progress made between 1985 and 1995, a period in which the use of trisilylmethanes inorganic synthesis really began to grow. Within the period 1993–2003, functionalized trisilylmethanesand related compounds have emerged as uniquely useful ligand precursors<1999MI267>. It has beenshown that the range of isolable organometallic compounds can be considerably extended by the useof ligands (XMe2Si)n(TMS)3�nCH (n=1–3) in which lone pairs from groups X can occupy sites in themetal coordination sphere. Moreover, the introduction of tripodal amino ligands of the type(RNHMe2Si)3CH into coordination chemistry has enabled the stabilization of new types of organo-metallic species with novel structural and reactivity patterns. In this chapter emphasis will be placedon the rapid and continuing developments, in the period 1993–2003, in the field of synthesis andreactions of the above compounds although most of that part of their chemistry which is concernedwith the synthesis of C-hetero-substituted derivatives will be covered in Chapter 6.13. Whereas muchinformation has been published about functions containing three metalloids, relatively little attentionhas been paid to functions bearing three metals. Nevertheless, despite the relative infancy of investiga-tions directed to the use of these species in organic synthesis, attempts have been made to summarizeand classify various compounds of the general formula (MLk)3CR.
To eliminate complications introduced by the kind of E and M, the consideration is restrictedhere to compounds (EXm)n(MLk)3�nCR, where C/E and C/M are bound via a �-bond. Carbor-anes, metal clusters, and �-metal complexes, of course, will not be treated.
6.06.2 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION(AND NO HALOGEN, CHALCOGEN, OR GROUP 15 ELEMENTS)
6.06.2.1 Synthesis of Functions Containing Three Metalloids
6.06.2.1.1 Functions bearing three silicons
The various methods available for the formation of 1,1,1-trisilylalkanes can be divided into fourcategories.
(i) ‘‘Direct synthesis’’ in the gas phase involving insertion of elemental silicon into acarbon�halogen bond of polychlorinated alkane such as chloroform (Equation (1)).
Cu (cat.) SiCl2X
SiCl2XXCl2SiCl3Si SiCl2Y
SiCl2X
H+ Others+ Si
n
+Cl
ClCl
X = H or Cl; Y = CH2SiCl2X; n = 1–3
ð1Þ
(ii) Reductive silylation of trihalomethanes (the Merker–Scott procedure) (Equation (2)).
X
XX
SiR3
SiR3R3Si+ nM +
X = Cl, Br; R = alk; M = Li (n = 6), Mg (n = 3)
3 SiX3Rð2Þ
(iii) Reactions of organometallic carbon nucleophiles such as a Grignard reagent or anorganolithium compound with halo- or alkoxy-silanes (Equations (3)).
SiR23R13Si
SiR33
SiR23Si+
X = Cl, Br, OAlk; R = Alk, Ar
–
–X– R13R33SiX ð3Þ
(iv) Derivatization and rearrangement of the compounds already containing polysilylatedcarbon or silicon units.
206 Functions Containing at Least One Metalloid (Si, Ge, or B)
When applicable, the Merker–Scott procedure is usually by far the most convenient and istherefore the method of choice. However, reactions of organometallic carbon nucleophiles withhalosilanes probably represent the most general approach, which has provided various routes totrisilylmethanes not readily accessible by other methods.
(i) Trisilylmethanes and their linear C-organyl derivatives, (X3Si)3CR
Direct reaction of elemental silicon with a mixture of CHCl3 and HCl has been studied in thepresence of a copper catalyst at various temperatures in the range 280–340 �C <1997OM93>.Tris(chlorosilyl)methanes with Si�H bonds were obtained as the major products along withbis(chlorosilyl)methanes, derived from the reaction of silicon with CH2Cl2 formed by the decom-position of CHCl3 (Scheme 1). A related preparation of the compounds Cl3�nMenSiCH(SiHCl2)2and Cl3�nMenSiCH(SiCl3)2 (n=0–3) has been described starting from the dichloromethylsilanesCl3�nMenSiCHCl2 <1994USP5332849, 1995USP5399740, 2000MI1020>.
Tris(trichloromethylsilyl)methane 1 has been obtained by the one-step synthesis presented inScheme 2. When CHCl3, SiHCl3, and Bun3N are allowed to react in the ratio 1:4.5:3, (Cl3Si)2CH2
is obtained in 90% yield; however, if a large excess (9 equiv.) of SiHCl3 is introduced in thereaction medium, the compound 1 is preferentially formed, isolated in ca. 30% yield as tris(ethoxy-silyl) derivative 2 after ethanolysis. The latter could then be metallated on the central carbon atomand trapped with MeI. With CO2, insertion and rearrangement afforded the stable ketene,[(EtO)3Si]2C¼C¼O <1998JOM(562)79>.
Interest in 1,1,1-tris(organylsilyl)alkanes has also continued. Tris(trimethylsilyl)methane,(TMS)3CH, and related compounds have been intensively studied in the late 1990s and early2000s in respect of their molecular geometry, ionization potentials, conformational structure, andmolecular dynamics <1999CEJ3501, 1999MI219, 1997OM5218, 2000JCS(D)4312,1994JCS(P2)2555>. Determination of the solution acidity of (TMS)3CH supports earlier findings<1994JA8304> that this compound is a significantly weaker acid (pK 36.8) than the correspond-ing silicon analog (TMS)3SiH (pK 29.4) <2002OM3157>. Consequently, (TMS)3CLi is a signifi-cantly stronger base than (TMS)3SiLi. This suggests that silicon accommodates a negative charge
SiHCl2
SiCl3Cl3Si
SiCl3
SiCl3Cl3Si
SiH2Cl
SiHCl2Cl2HSi
SiHCl2
SiHCl2Cl2HSi
SiCl3
SiHCl2Cl2HSiCHCl3 + HCl + Si Cu/Cd
+ High boilers + Bis(chlorosilyl)methanes
12% 17%trace3%
16%45%6%
+
++300 °C +
Scheme 1
Cl
ClCl
Si(OEt)3
Si(OEt)3(EtO)3Si
Si(OEt)3
Si(OEt)3(EtO)3Si
SiCl3
SiCl3Cl3Si
[(EtO)3Si]3CMe
+ 3SiHCl3 + 3Bun3N
iii30%
1
iii iv95%
–
2
i. MeCN, –40 °C; ii. EtOH, –40 °C; iii. ButLi, THF, –80 °C; iv. MeI, THF, –80 °C
Scheme 2
Functions Containing at Least One Metalloid (Si, Ge, or B) 207
much more effectively than carbon, despite its lower electronegativity (C 2.5, Si 1.7). Reich andco-workers have prepared 13C-labeled tris(TMS)methane from commercially available 13C-para-formaldehyde (Scheme 3). This synthesis involves several in situ electrophilic traps, which takeadvantage of the differing reactivities of the starting materials, products, and electrophiles towardmetallating agents <1998MRC118>.
A modification of the Merker–Scott procedure, involving the reaction between CHBr3, R3SiCl,and BunLi has been extended to numerous sterically crowded tris(organyl)chlorosilanes; anexample is the preparation of the tris(i-propyldimethylsilyl)methane (Equation (4)). The lattercan be used to attach the bulky trisilylmethyl group to a metalloid or metal center, wasdemonstrated by treating the lithium reagent, (PriMe2Si)3CLi, with Me2HSiCl to give a 77%yield of (PriMe2Si)3CSiMe2H <1995JOM(489)181>. Other examples relate to trisilylmethanes(RMe2Si)3CH (R= o-Tol, Et) <1996JOM(510)117, 1998JOM(555)263>. Metallation of(o-TolMe2Si)3CH by MeLi in tetrahydrofuran (THF) was shown to be much slower than thatof (PhMe2Si)3CH. The lithium salt reacts with MeI to give (o-TolMe2Si)3CMe, but neither withMe2SiHCl nor with a range of other organosilicon halides <1996JOM(510)117>. A furtherextension of this type of chemistry was the development of arene-catalyzed lithiation of poly-chlorinated compounds under the Merker–Scott conditions. The reaction of 1,1,1-trichloro-alkanes with a large excess of lithium metal (1:20 molar ratio) in THF in the presence ofchlorotrimethylsilane and a catalytic amount of 4,40-di-t-butylbiphenyl (DTBB) was found toproduce 1,1,1-trisilylalkanes in good yield (Equation (5)). Conditions for preparing the mono-and disilylated compounds have also been described <1996T1797>.
Br
BrBr
SiMe2Pri
SiMe2PriPriMe2Si+ 3PriMe2SiCl + 3BunLi
60%
–78 °C, THFð4Þ
Cl3CR (TMS)3CR51–93%
TMS–Cl, Li (1:20), DTBB (5 mol.%)
R = H, D, Me, Ph
DTBB = 4,4'-di-t-butylbiphenyl
ð5Þ
The obvious thought of using combination of the Merker–Scott procedure and the reaction of anorganolithium compound with the corresponding halosilane for the synthesis of trisilylmethaneswith different silyl groups attached to the carbon atom was realized for the compounds 4 and 5<1997OM4728>. Treatment of CHBr3 at low temperature with 3 equiv. of BunLi in the presenceof 3 equiv. of Me2PhSiCl gave trisilylmethane (PhMe2Si)3CH. When 2 equiv. of Me2PhSiCl/Bu
nLiwas used, the product was bromodisilylmethane 3, and this was converted into trisilylmethane 4 bytreatment with BunLi/TMS-Cl. In the same way, the compound 5 was obtained by use of 2 equiv. ofTMS-Cl/BunLi in the first step and 1 equiv. of BunLi/Me2PhSiCl in the second step (Scheme 4). Goodyields could be obtained at each stage, provided the temperature was rigorously controlled.
The attachment of the very bulky (PhMe2Si)3C ligand or of the closely related (TMS) (Me2PhSi)2Cand (TMS)2(Me2PhSi)C ligands to a metal center made possible the isolation of a number of metalderivatives (TMS)3�n(Me2PhSi)nCM: n=1, M=Li(tetramethylethylenediamine [1,2-bis(dimethyl-amino)ethane] (TMEDA)), Li(Et2O), Na(TMEDA); n=2, M=Li(THF)2, Li(TMEDA), K; n=3,
TMSC13
SePhTMS
C13H2PhSe
PhSe
TMSC13
TMSTMS
TMSC13
SePhPhSe(C13H2O)n + PhSeH
ii iii97%
iv90%
i 100%crude yield
81%
i. BF3·OEt2,CHCl3, 0 °C, 4 days; ii. TMS–Cl, LDA, THF, –78 °C, 2 h;iii. BunLi, THF, –78 to –20 °C, TMS–Cl
Scheme 3
208 Functions Containing at Least One Metalloid (Si, Ge, or B)
M=Rb or Cs <1997OM4728>. For further details of this subject, readers are referred to thefollowing articles and references therein <1998JOM(564)215, 1997OM5653, 1996JOM(510)143>.Eaborn and co-workers have subsequently introduced the closely related dicarbanionic ligand[C(TMS)2SiMe2CH2CH2Me2Si(TMS)2C] (R-R) <1999OM2342>. Its precursor HR-RH 6 was pre-pared by the reaction shown in Scheme 5 <1996OM1651>. The compound 6 was metallated withMeLi in THF in the presence of TMEDA to give the chelated salt 7. If no TMEDA is added, a solidcompound, assumed to be [(R-R)Li], may be isolated in 80% yield from diethyl ether/hexane. Thelithium salt can be used to make cyclic derivatives of mercury <1996OM1651>, lead<1997OM5621>, potassium, zinc, ytterbium, tin <1999OM2342>, manganese, and cesium<2000OM1190>. The structurally related disiloxane [(TMS)2CHMe2Si]2O has also been prepared,and shown to undergo metallation reaction leading to a novel molecular species incorporating a cyclicorganolithate anion and disiloxane-solvated lithium cation <1998CC1277>.
The reaction of (TMS)2CHLi with hexachlorodisilane has been explored as a means of synthesiz-ing tetrachlorodisilane 8 <2001IC3766>. Starting from 8 a wide variety of 1,2-bis[bis(TMS)methyl]-substituted disilanes were prepared (Scheme 6). A reduction of 8 with LiAlH4 resulted in theformation of the disilane 9 and the metathesis with Me3SnF yielded the tetrafluorodisilane 10.The interaction of 8 with a solution of sodium in liquid ammonia at �78 �C affords the tetra-aminodisilane 11. In turn, treatment of 11 with reagents containing acidic protons (HBr, HI, orH2O) leads under elimination of NH3 to the tetrabromo- 12, tetraiodo- 13, and tetrahydroxydisilane14. The silicon�silicon bonds were not cleaved under these conditions. The disilane 14 can also beobtained directly from the reaction of tetrachlorodisilane 8 with a mixture of H2O2/H2O. However,in contrast to 8, the tetraaminodisilane 11 reacted under the same conditions to yield thetrihydroxycyclotrisiloxane 15 <2002OM3671>. The synthetic utility of 11 has also been demon-strated by the reaction with liquid H2S at �70 �C leading to the formation of a S4Si4 cagecompound 16 <2001OM1282>. The driving force for the crossover arrangement of the sulfuratoms is most likely the formation of the four five-membered rings. Finally, a somewhat similarchemistry was performed with (TMS)2CHSiCl3. The ammonolysis of this compound with ammoniawhich was not predried with sodium yielded the trihydroxycyclotrisilazane 17 while the reactionwith sodium in predried ammonia gave the acyclic tetraaminodisilazane 18 <2000EJI827>.
Br
BrBr
Br
TMSTMS
Br
SiMe2PhPhMe2Si
Li
TMSTMS
Li
SiMe2PhPhMe2Si
SiMe2Ph
TMSTMS
TMS
SiMe2PhPhMe2Siii iii
3
ii v
5
i
4
iv
i. 2PhMe2SiCl/2BunLi, THF, –80 °C; ii. BunLi, Et2O, –78 °C; iii. TMS–Cl, Et2O, –78 °C;
iv. 2TMS–Cl/2BunLi, THF, –80 °C; v. PhMe2SiCl, Et2O, –78 °C
Scheme 4
LiTMS
TMSClMe2Si SiMe2Cl
Me2Si
Li
SiMe2
TMSTMSTMSTMS
Me2Si SiMe2TMS
TMSTMS
TMS
7
6
[Li(TMEDA)2]+MeLi/ TMEDATHF, 6 h, 20 °C 69%
+THF, reflux, 4 h
82%2
Scheme 5
Functions Containing at Least One Metalloid (Si, Ge, or B) 209
Si
NH2
HN NH2Si
RH2N
NH2
RSi
NHSiHN
Si NH
R
OH
OHR
RHO
OSiO
Si OSi
R
OH
OHR
HOR
Si
Si
SS
SS
Si
SiR
R
R
R
15 16 17 18
R = (TMS)2CH
(ii) Functionalized trisilylmethanes containing an ‘‘active’’ ligand framework
The extreme exploitation of the steric demand of an Si3C function is a common feature of most ofthe early reports on trisilylmethane chemistry <1996CCR125, 1995JOM(500)89>. The emphasisin studies on trisilylmethane derivatives has moved toward polydentate compounds of the type(XMe2Si)3�n(TMS)nCH, n=0–2, in which the trisilylmethyl ligands have bulk similar to that ofthe (TMS)3C, but contain groups X bearing heteroatoms with lone pairs capable of coordinatingintra- or intermolecularly to the metal. The most prominent example of the versatility of thisconcept is the structural chemistry and chemical reactivity of a series of compounds studied byEaborn and co-workers. Those include functionalized trisilylmethanes (Me2NMe2Si)(TMS)2CH<1999OM45>, (Me2NMe2Si)3CH <1996CC741, 1997OM503, 1998OM3135>, (MeOMe2Si)(TMS)2CH <1996JOM(521)113, 1996OM4783, 1997AG(E)2815, 1997OM5653, 1998OM4322>,(MeOMe2Si)3CH <1992JCS(D)1015>. Typically the compounds (XMe2Si)3�n(TMS)nCH areobtained in several steps via the corresponding bromosilanes. Representative examples are givenin Scheme 7 <1999JCS(D)3267>. Interestingly, the reaction between compound 19 and BunLiproceeded much faster than the corresponding reaction with (TMS)3CH suggesting that it isfacilitated by initial coordination of Me2N to lithium. The compound 20 reacted with MeLi at0 �C to give a complex mixture that, after aqueous work-up, was found to contain (MeOMe2Si)(TMS)2CH, indicating that MeLi had attacked Si�OMe as well as C�H bonds. However, thereaction between 20 and Pri2NLi proceeded smoothly at �60 �C and the lithium compound(MeOMe2Si)2(TMS)CLi was isolated in good yield.
The symmetrically substituted tris(aminosilyl)methanes (RNHMe2Si)3CH are available fromthe reaction of (BrMe2Si)3CH 21 with 3 equiv. of a primary amine in the presence of an excess oftriethylamine as auxiliary base. The facile accessibility of these compounds along with thepossibility of preparing enantiomerically pure derivatives provided the motivation for the synth-esis of an extensive series of novel trisilylmethane-derived tripodal amines and the correspondingtrilithium triamides (Scheme 8). A comprehensive study into the coordination chemistry of
Si SiF
F
F
F TMS
TMSTMS
TMSSi Si
Cl
Cl
Cl
Cl TMS
TMSTMS
TMS
Si SiNH2
NH2
NH2
NH2 TMS
TMSTMS
TMSSi Si
X
X
X
X TMS
TMSTMS
TMS
LiTMS
TMS
Si SiTMS
TMSTMS
TMS
H
H
H
H
10
+ Si2Cl6 53%i ii
85%
8
12, X = Br
13, X = I
14, X = OH
v–vii
74–86%
119
iv 82%76%ii
i. toluene, reflux, 6 h; ii. LiAlH4, THF, –78 °C; iii. Me3SnF, toluene, reflux, 15 min;
iv. Na /NH3, –78 °C; v. HBr, toluene, 20 °C, 30 min; vi. HI, toluene, 20 °C, 30 min;
vii. H2O, THF, reflux, 20 h
Scheme 6
210 Functions Containing at Least One Metalloid (Si, Ge, or B)
these ligands has been carried out by Glade and co-workers <2002JCS(D)2608, 2001CEJ2563,2001EJI1425>. Interestingly, the tris(aminosilyl)methanes were found to be in equilibrium insolution with the cyclic diamines, which are generated upon ejection of one molecule of theprimary amine. Reaction of these equilibrium mixtures with 3 equiv. of BunLi affords thetrilithium triamides. It is notable that the result of the metallation is the same whether thereaction is carried out with the essentially pure tripodal amine or with a mixture of the triamineand the cyclic product in the presence of the dissociated primary amine (Scheme 9)<2001CEJ2563, 2001MI191,1994IC3064>.
Tris(diphenylphosphinodimethylsilyl)methane 22 has been prepared from the reaction of 21 andPh2PLi (yield 62%) <1999CJC1931> or Ph2PK (89%) <1999JCS(D)831>. The compound 22reacted with [Mo(CO)6] to give the complex cis-23, in which two phosphine groups are coordinatedto molybdenum and one is free and with BunLi in the presence of TMEDA to give [Li(TME-DA)2][(Ph2PMe2Si)3C] which contains discrete planar carbanions and no Li�P coordination
TMS
SiMe2PhPhMe2Si
TMS
SiMe2BrBrMe2Si
TMS
SiMe2XXMe2Sii ii or iii
19, X = Me2N
20, X = MeO
4
i. Br2/Al, petroleum, 2 h, 0 °C; ii. Me2NH, petroleum, –60 °C, 84%;
iii. MeOH/Et3N, petroleum, 20 °C, 83%
Scheme 7
H
Me2Si SiMe2SiMe2
BrBr Br
THF
MgH
Me2Si SiMe2SiMe2
HH H
H
Me2Si SiMe2SiMe2
NHNH NHRR R
R = But <1993IC2308>, Ph <1994IC3064>, 2-FC6H4 <1995IC4062>, 4-FC6H4, 2-MeC6H4,
3-MeC6H4, 4-MeC6H4 <1994IC3064>, 2-MeOC6H4 <2002EJI1968>, 4-methyl-2-pyridyl,
4,6-dimethyl-2-pyridyl <1997OM5585>, (S)-Ph(Me)CH <1994IC3064, 1996OM3637,
2001CEJ2563>, (R)-4-MeOC6H4(Me)CH <2001MI191>, (R)-1-tetralenyl <2001JCS(D)964>,
(S)-But(Me)CH <2001EJI1425>, (S)-1-(1-naphthyl)ethyl <2002PO629>, (R)-1-indanyl <2001CEJ2563>
HCBr3 + 3Me2Si(H)Cl
3RNH2, 3Et3N
21
3Br2
Scheme 8
H
Me2Si SiMe2SiMe2
NHNH NHRR R
H
Me2Si SiMe2SiMe2
N NHRR
RNH2
BunLi
H
Me2Si SiMe2SiMe2
NN NRR LiLi R
Li
R = (S)-Ph(Me)CH, (R)-1-indaryl, (R)-4-MeOC6H4(Me)CH
+
Scheme 9
Functions Containing at Least One Metalloid (Si, Ge, or B) 211
<1999JCS(D)831>. The susceptibility of 22 to cleavage of the P�Si bonds by protic reagents hasalso been described <1999CJC1931>. Hydrolysis of the P�Si bond in 22 produces principally thealcohol 24. In the presence of excess of methanol, the compound 22 is cleanly converted to thetrisilylmethane 25. Bubbling oxygen through solutions of 22 for 15min gives only trace amounts ofthe oxidation product 26 (Scheme 10).
Other examples of this type of functionalized trisilylmethanes are (Ph2PCH2Me2Si)3CH,(Ph2PCH2Me2Si)2(TMS)CH, and (Ph2PCH2Me2Si)(TMS)2CH <2000JCS(D)2183>. The conver-sion of triphosphino derivative to the corresponding lithium salt was affected by MeLi in ether.The anionic ligand in compound (Ph2PCH2Me2Si)3CLi shows a close skeletal resemblance to thetripodal ligands in silatranes, but the coordination to the metal center is provided by the lone pairof electrons of the carbanion rather than by that of the nitrogen atom.
The [dimethyl(2-pyridyl)silyl]-bis(TMS)methane, (2-PyMe2Si)(TMS)2CH, containing a nitrogenatom in its ligand periphery was synthesized by reaction of (BrCH2Me2Si)(TMS)2CH with2-lithiopyridine (yield 61%). This ligand precursor reacts with MeLi in THF to give the lithiumderivative, which could be used to obtain compounds of a wide range of metals (K, Mg, Cr, Mn,Co, Ni) <2000OM3224, 2000CC691>. Synthesis of more sophisticated trisilylmethane-basedpolydentate species is shown in Scheme 11. Preparation of the compound 27 was readily achieved byreaction of 3 equiv. of propynyl lithiumwith 1 equiv. of 21. Reaction of this precursor with an excess ofthe 4,6-di-t-butyl-1,3,2-diazaphosphinine yields intermediate 28. In a subsequent step, 28 was reactedwith trimethylsilylacetylene to give the desired ligand 29. Complex of 29 with [Mo(CO)5(THF)] hasalso been characterized <2000EJI2565>.
(iii) Compounds with an Si3C function as part of one or more ring systems
Tris(aminosilyl)methanes, HC(SiMe2NHR)3, have been shown to be valuable starting materials tobuild up compounds in which the trisilylmethane unit is part of a hetero-bicyclo[2.2.2]octanesystem. After lithiation with n-butyllithium, these amines react with early transition metals(Y <1995IC4062>, Ti <1997OM5585, 2001CEJ2563>, Zr <1995IC4062, 1999JOM(591)71,2000OM963, 2001EJI1425>, Hf <1999JOM(591)71>, Nb <1997OM5585>) as well as groups 13(Tl <2001CC899>, Sn and Pb <1995IC4069, 1995CB29, 1998POL737, 2001ZAAC(627)1417>)and 15 (Sb, Bi <2000IC3931>) metals to form complexes with tripodal amido ligands. Someexamples taken from the studies by Gade and co-workers are shown in Scheme 12. Relatedhetero-bicyclo[2.2.2]octanes containing chalcogens instead of the nitrogen atoms are formed in asmooth reaction from easily available HC(SiMe2Cl)3, RMCl3 (M=Si, Ge, or Sn), and a suspensionof Li2E (E=S or Se) in THF (Scheme 13) <2002JOM(660)27>.
A new synthetic approach toward hexasilabicyclo[2.2.2]octane system, in which three Si�Silinkages are aligned in parallel between two bridgehead carbons, is conceptually based on triplesilylation of two molecules of a trilithiomethane equivalent with three molecules of dichlorodisilanes
H
Me2Si SiMe2SiMe2
PPh2Ph2P PPh2
Mo(CO)6
H
Me2Si SiMe2SiMe2
PPh2Ph2P PPh2
(OC)4Mo
H
Me2Si SiMe2SiMe2
XX X
Toluene, reflux90%
HX or O2
Toluene, 20 °C
22 23
24, X = OH
25, X = OMe
26, X = OP(O)Ph2
Scheme 10
212 Functions Containing at Least One Metalloid (Si, Ge, or B)
HCBr3
H
Me2Si SiMe2SiMe2
Me Me Me
NP
N
But But
H
Me2Si SiMe2SiMe2
PP
MeMe
P
TMS TMSTMS
H
Me2Si SiMe2SiMe2
BrBr Br
H
Me2Si SiMe2SiMe2
PNN
P
But
Me
But
Me
NP
But
Li
Toluene, 100 °C, 3 h
27
28
Toluene, ∆
29
3Me
3
3TMS
21
i. 3Me2SiHCl, Mg, THF
ii. Br2, benzene THF, –78 °C
–3ButCN
–3ButCN
Scheme 11
H
Me2Si SiMe2SiMe2
NN NRR LiLi
R
Li
(OEt2)2 M = Sn, PbM = Sb, Bi
TlCl3 ZrCl4 MCl3
H
Me2Si SiMe2SiMe2
NN NRR
ZrR
Li(THF)n+
H
Me2Si SiMe2SiMe2
NN NRR
MR –
H
Me2Si SiMe2SiMe2
NN NRR
MR
H
Me2Si SiMe2SiMe2
NN NRR
TlR
ClLi
Cl
MCl2
Scheme 12
TMS
TMS TMS
SiMe2Cl
ClMe2Si SiMe2Cl
R-MCl3/3Li2E
Hexane, rt
45–70%
3MeCOCl/AlCl3
82%
M = Si, Ge, Sn; E = S, Se; R = Me, Ph, H2C=CH–
H
Me2Si SiMe2SiMe2
EE E
MR
Hexane, 0 °C
Scheme 13
Functions Containing at Least One Metalloid (Si, Ge, or B) 213
as illustrated in Scheme 14. Commercially available bis(phenylthio)methane was selected for atrilithiomethane equivalent because the phenylthio group facilitates deprotonation and stabilizesthe anionic center. Moreover, the group is readily removed by metallation to give rise to the lithiumderivative. Reduction of the disilane 30 with lithium radical anion and its silylation with (ClSiMe2)2lead to 1,2,4,5-tetrasilacyclohexane 31 as a stereoisomeric mixture (cis:trans=1:1). Final ringformation for hexasilabicyclo[2.2.2]octane 32 was attained by reduction of 31 and subsequentsilylation with (ClSiMe2)2 <1998CL1145>.
Functionalization of 32 at bridgehead carbon was achieved by treatment with BunLi-ButOKfollowed by a reaction with electrophile (Scheme 15). It is noteworthy that only monosilylationoccurs. Probably through-space or through-bond electrostatic interaction prevented the formationof a bridgehead dianion. Nevertheless, a stepwise procedure involving deprotonation of 32followed by electrophilic quenching allowed preparation of symmetrically or dissymmetricallydisubstituted derivatives <2000JOM(611)12, 2001CL1090>.
Further extension of this synthetic strategy is illustrated in Scheme 16. Synthesis of cagecompounds 36 and 37 containing a trisilane linkage was achieved starting from the acyclictrisilane 33. Reduction of 1,3,4,5-tetrasilacyclohexane 34 with lithium radical anion effectivelyproduced 1,3-dimetallic reagent 35 which, upon quenching with Me2SiCl2, gave pentasilabi-cyclo[3.1.1]heptane 36. Silylation of 35 with Cl(SiMe2)2Cl also proceeded successfully, givingrise to 2,3,4,6,7,8-hexasilabicyclo[3.2.1]octane 37 <2000JOM(611)12>.
The reaction of tris[dimethyl(ethynyl)silyl]methane with triethylborane was reported to proceedvia a threefold 1,1-ethylboration to give a bicyclic compound incorporating trisilylmethane unit<1995CC399>.
6.06.2.1.2 Functions bearing three borons
The first synthesis of triborylmethane derivatives was reported in 1968, by Matteson and Castle whoobtained tris(dimethoxyboryl)methane, CH[B(OMe)2]3, by treatment of (MeO)2BCl and CCl4 with
BuLi (ClSiMe2)2
(ClSiMe2)2
Li+
2 2THF, 0 °C –78 °C to rt
94%30
LDBB
LDBB
32
82%
LDBB =
-
31 (1/1 cis/trans)
LiPhS
PhS
PhS
PhSSi
PhS
PhSSi
SPh
SPh
SiSi
Si SiSPhPhSSi
Li
PhSSi
Li
SPh
SiSi
Si SiLiLi
(ClSiMe2)2
73% Si
Si Si
SiSi
Si
H
H
THF, –78 °C
Scheme 14
214 Functions Containing at Least One Metalloid (Si, Ge, or B)
lithium in THF <1968JA2194>. Subsequently, tris(dichloroboryl)methane, CH(BCl2)3, was synthe-sized by an exchange reaction of tris(dimethoxyboryl)methane with boron trichloride <1973IC2472,1995COFGT(6)171>. Siebert and co-workers have reported the synthesis of 1,1,1-tris(dichloroboryl)-alkanes and tris(boronate)esters via hydroboration of alkynylboronates using in situ generated HBCl2<2001EJI373, 2002EJI1293>. In addition, Marder and co-workers have described a catalytic route tothe tris(boronate)esters in a single step from readily accessible vinylboronates <2002JOM(652)77>.New acyclic systems bearing three dialkylboryl groups on a single carbon atom have also beenprepared <1998AG(E)1245>.
Si
Si Si
SiSi
Si
H
H
Si
Si Si
SiSi
SiMe
TMS
Si
Si Si
SiSi
Si
H
M
Si
Si Si
SiSi
Si
H
TMS
RXSi
Si Si
SiSi
Si
H
R
BunLi-ButOK
32
THF, –42 °C
i. BunLi-ButOK
ii. MeI
RX, R, yield: MeI, Me, 97%; CH2=CHCH2Br, CH2=CH–CH2, 94%;PhCH2Br, PhCH2, 85%; Me2PhSiCl, Me2PhSi, 90%;Me2[Cl(CH2)3]SiCl, SiMe2[(CH2)2Cl], 86%; Bu3SnCl, Bu3Sn, 88%;(PhS)2, PhS, 62%; I2, I, 77%
Scheme 15
Si
Si
SiSi
Li Li
Cl(SiMe2)2Cl
Si SiSi
SiH
H
SiSi
Si
Si
SiSi
PhS SPh
Me2SiCl2
Li+
Si SiSi Si
SiH
H
SiSi
Si
PhS SPh
LDBB
THF, –78 °CTHF, –78 °C
–40 °C, 62%63%, –40 °C
34 35
36 37
LDBB =
-
33
i. BuLi-ButOKii. Me2SiCl2
Scheme 16
Functions Containing at Least One Metalloid (Si, Ge, or B) 215
(i) 1,1,1-Tris(dihaloboryl)alkanes
1,1,1-Tris(dichloroboryl)-3,3-dimethylbutane 38 is now readily available on a large scale bylithiation of 3,3-dimethyl-1-butyne by n-butyllithium, followed by boron/lithium exchange withBCl3 and a double hydroboration of the boryl alkyne with dichloroborane (HBCl2) preparedin situ (Scheme 17). This reaction sequence afforded a 42% yield of 38 <2002EJI1293>. Treatmentof trimethylsilylacetylene with BunLi, BCl3, and 2 equiv. of HBCl2 provided 1,1-bis(dichloroboryl)-2-trimethylsilylethene 40 and isomeric products 41–43 (Scheme 18) <2002EJI1293>. Presumably,the hydroboration of 39 occurs regioselectively to give bis(dichloroboryl) derivative 40. Dichlor-oborane then hydroborates 40 in both directions, giving rise to the compounds 41 and 42, with theformer being favored. The mechanism of the formation of 43 is unclear.
(ii) Methanetriboronic esters
The preparation of tris(ethylenedioxyboryl)methane 45, a reagent for the homologation of alde-hydes and ketones under nonacidic conditions, was improved by avoiding the isolation of theintermediate tris(dimethoxyboryl)methane. The compound 45 is best prepared from thedimethoxyboron chloride, chloroform, and lithium dispersion by transesterification of crudemethyl ester 44 with ethylene glycol and subsequent crystallization of the product from hotTHF (Scheme 19) <1995T11219>.
i, ii iii42%
38
BCl2
BCl2
BCl2BCl2
i. BunLi, pentane, –15 °C; ii. BCl3, pentane, –78 °C;
iii. BCl3/Me3SiH (2 equiv.), pentane, –30 °C
Scheme 17
TMS TMS BCl2 +
+ +
i. BuLiii. BCl3
–LiCl
40
41 42 43
TMS
BCl2
BCl239
BCl2
BCl2BCl2
TMS BCl2
BCl2
TMS
Cl2B BCl2
TMS
Cl2BCl2B
2HBCl2
Scheme 18
+ 3ClB(OMe)2 + 6LiTHF, 0 to 70 °C 16%
44 45
Cl
Cl ClOHHO
B
B B
OO
O
O O
O
B
B B
MeO OMe
OMe
OMe
MeO
OMe–30 to 20 °C
Scheme 19
216 Functions Containing at Least One Metalloid (Si, Ge, or B)
Knowledge of the versatile reactions of boranes with unsaturated compounds prompted aninvestigation into the synthesis of methanetriboronic esters via alkynes. Siebert and co-workershave shown that the interaction of the catechol-substituted monoborylacetylene 46 withan excess of 1,3,2-benzodioxaborole (catecholborane) leads to a mixture of 1,1-bis(1,3,2-benzo-dioxaborol-2-yl)ethene 47 and a small amount of trans-1,2-bis(1,3,2-benzodioxaborol-2-yl)-ethene 48. In contrast with catecholborane, dichloroborane adds to 47 affordingtriborylethane 49, which was identified as a catechol ester 50. The direct hydroboration of 46with 2 equiv. of HBCl2 and subsequent reaction with catechol also affords 50 in 83% yield(Scheme 20) <2001EJI373>.
The transition metal-promoted catalytic diboronation of diborylacetylenes offers anothernew route to compounds containing a B3C function <1999EJI1693>. Thus in refluxingtoluene, the platinum complexes [Pt(PPh3)2(C2H4)] or [Pt(PPh3)4] catalyze the doublediboronation of the diborylacetylene 51 with the catechol-substituted diborane 52 to give thehexaborylethane 53 (Scheme 21). Reaction conditions were found to be critical; the formationof tetraborylethane 54 instead of hexaborylethane occurs by catalysis with [Pt(PPh3)2(C2H4)]or [Pt(PPh3)4] in THF at 55 �C. Moreover, the tetraborylethene 55 is obtained from 51 and 52with the base-free platinum complex [Pt(COD)2] under mild conditions in toluene. At tem-peratures above 40 �C 55 adds 52 to form hexaborylethane 53. Hexaborylethane derivativeshave also been obtained from the diborylacetylene 56 and the diborane 52. However, thereaction leads to a mixture of naphthalene- and benzo-1,3-dioxa-2-borol-2-ylethanes, in whichbetween five and two boryl substituents of 52 and between one and four substituents of 56 areincorporated. It is unclear whether the exchange occurs before or after the formation of thehexaborylethanes.
The route employing transition metal-catalyzed diboration of borylalkenes appeared to bea general method for synthesizing tris(boronate)esters, as further examples demonstrate.Diboration of the styrylboronate esters 57 with diborane 52 in the presence of a variety ofrhodium phosphine catalysts gives predominantly either 58, which contains three boronateester groups on the carbon atom, or its isomer 59. Wilkinson’s catalyst, [Ph(PPh3)3Cl], gavethe highest yield of 58, 75% and 71% for 58a and 58b, respectively, with the reactionsessentially going to completion (Equation (6)). The formation of 58 apparently involvesregiospecific insertion of the vinylboronates into a Rh�B bond followed by �-hydride
OB
O+
OHB
O
Bcat =
O–B
O
catB+
HBCl2
OH
OH
OH
OH2
–4HCl –2HCl
78%
47 48
4950
Bcat
46
MeBcat
BcatBcat
Bcat
Bcat
MeBCl2
BcatBCl2 Me
Bcat
BcatBCl2
80 °C
2HBCl2
Scheme 20
Functions Containing at Least One Metalloid (Si, Ge, or B) 217
elimination, another regiospecific insertion of the 2,2-vinyl bis(boronate) into the remainingRh�B bond followed by C�H reductive elimination leading to 2,2-diboration and a2,1-hydrogen shift <2002JOM(652)77>.
OB
O O
OB
52 57
+
58 59
Ar = Ph (a), 4-MeOC6H4 (b); Bcat =
Ar
Bcat
Ar
Bcat
BcatBcat
Ar
Bcat
Bcat
O–B
O
Rh(PPh3)3Cl (1 mol.%)
+
catB
THF, 58 °C, 12 h
ð6Þ
(iii) Tris(boryl)alkanes and boracycloalkanes involving a B3C function
1,1,1-Tris(diethylboryl)alkanes have been postulated and evidenced in many reactions of boryl-acetylenes with diethylborane <1994AG(E)2296, 1995CC1691, 1998AG(E)1245>. For example,hydroboration of trimethyl(propyn-1-yl)silane with Et2BH under ‘‘hydride bath’’ conditions (i.e.,with a large excess of diethylborane) leads to the 1-carba-arachno-pentaborane(10) derivative 64.The reaction proceeds via intermediate formation of compounds 60–63. In the hydride bath,exchange reactions between in situ generated 1,1,1-tris(diethylboryl)propane 62 and geminalbis(diethylboryl)alkane 63, take place until the carborane skeleton 64 is formed (Scheme 22)<1997CCC1254>.
A thermally stable tris(boryl)ethane has been derived from the interaction of 50 witht-butyllithium. This reaction results in the formation of 1,1,1-tris[di(t-butyl)boryl]ethane 65,which does not form any closo-C2B3 carborane by elimination of trisorganoboranes (Equation (7))<2001EJI373>.
OB
O O
OB
+(Ph3P)2Pt(C2H4)
Toluene, reflux, 24 h
71%
catB
catB
Pt(COD)2
70%
Bcat
H
BcatcatB
catB
51
5253
52 >40 °C
55
5654
OB
OB
O
O
Bcat
Bcat
catBcatB
catB Bcat
BcatBcat
(Ph3P)2Pt(C2H4)
OB
OB
O
O
Bcat =
O–B
O
H
Toluene, 40 °C, 48 h55 °C, 24 h
Scheme 21
218 Functions Containing at Least One Metalloid (Si, Ge, or B)
Me
tBu2B
Bu2B
Bu2Bt
t
Me
catB
catB
catB
50 65
Bcat = O
–BO
–3C6H4O2Li2
6ButLi
ð7Þ
Siebert and co-workers also found that cyclic tetraborylmethane 67 is formed in excellent yieldupon addition of B2Cl4 to a solution of boriranylideneborane 66 in hexane at low temperature.The substitution of the chlorine atoms of 67 by amino groups yields the triamino derivatives 68with unexpected cleavage of one of the exocyclic C�B bonds (Scheme 23) <2001EJI387>.
A route to boracycloalkanes possessing closo-C2B3 carborane structure, which may be describedas midway between classical and nonclassical, uses thermolysis of the triborylalkane 38. Onheating neat 38 at 170 �C, elimination of BCl3 occurred with formation of the compound 69.
TMS Me Et2BH
Et2B MeEt2B
MeTMS
Et2BH
Et2BEt2B
Et2BEt
Et2B
TMS
Et
Et2B
3Et2BH
BB H
B
HB
H
Et
Et
Et Et
EtEtMe2HSi
+
+
+
62 63
64
–4BEt3
60 61
Scheme 22
B2Cl4
Hexane, –85 °C 92%
HNEt2 or
TMS–NMe2 or
2LiN(CH2)4
Hexane, –30 °C32–48%
66 67 68
R2N = Me2N, Et2N, N
B BBut
TMS
TMS
ButB
B B
BTMS
TMS
Cl
Cl
ClCl
But
But
B
B H
BTMS
TMS
NR2
NR2
NR2
But
Scheme 23
Functions Containing at Least One Metalloid (Si, Ge, or B) 219
Methylation of 38 with Al2Me6 gave 70, which, on heating, was transformed into 71. The latterwas also formed by direct methylation of 69 with MeLi or Al2Me6. Treatment of 69 with3,3-dimethylbutynellithium and 2-phenylethynyllithium afforded 72a and 72b, respectively (Scheme24). Attempts to substitute the chloro atoms with OH, OMe, OBut, and catechol groups wereunsuccessful. With sterically demanding lithium, reagents such as ButLi, Pri2NLi, BunLi, and PhLionly product mixtures were obtained <2002EJI1293>.
6.06.2.1.3 Functions bearing three germaniums
Traditionally, trigermylmethane derivatives are synthesized either via condensation of the poly-lithiated hydrocarbons with chlorotrimethylgermane or via stepwise base-assisted introduction ofan R3Ge group into compounds containing an activated methyl group <1995COFGT(6)171>.
Kouvetakis and co-workers have utilized the high reactivity of dihalogermylenes towardC�Hal bonds to develop probably the most general and effective synthesis of simple trigermyl-methanes <1995IC5103, 1996CM2491, 1998JA6738>. They found that the germylene complexesGeX2
.dioxane (X=Cl, Br) undergo complete insertion into the C�Br bonds of CBr4 to give thetetrakis(trihalogermyl)methanes 73 and 74, in 79% and 94% yields, respectively. Reduction of 73with LiAlH4 in a very high boiling solvent (C30H50 squalene) in a two-phase system with a phasetransfer catalyst leads to the tetrakis(germyl)methane 75 in 20% yield. A substantial quantity(18% yield) of 76, the tris(germyl) analog, is also obtained as a by-product. The reduction of 74with LiAlH4, under conditions similar to those for the reduction of 73, leads to compounds 75and 76 in 1:1 molar ratio in approximately 12% yield each (Scheme 25) <1998JA6738>.
–BCl3
Al2Me6hexane, –78 °C 83%
–BMe3toluene, reflux, 2 h
R Li
Hexane, –78 °C 62–67%
R = But (a), Ph (b)
38
69 72a,b
71
70
Et2O, –70 °C
75%
BBB
But
But
ClCl
ClB
BB
But
But
RR
R
BBB
But
But
MeMe
Me
BMe2
BMe2BMe2
But
BCl2
BCl2BCl2
But
MeLi or
Al2Me6
170 °C, 2 h; 25%
Scheme 24
CBr4 Toluene
73, X = Cl
74, X = Br
75 76
+GeX2Br
BrX2Ge GeX2BrGeX2Br
GeH3
H3Ge GeH3GeH3
GeH3
H3Ge HGeH3
4GeX2·diox LiAlH4
Scheme 25
220 Functions Containing at Least One Metalloid (Si, Ge, or B)
A more attractive synthesis of the trigermylmethane 76 is based on the direct reduction oftris(tribromogermyl)methane. The bromide 77 in turn is prepared by direct insertion of GeBr2into the C�Br bonds of bromoform (Scheme 26) <1996CM2491>.
Trigermylmethane 76 is a stable, colorless liquid, and its relatively high volatility makes ithighly suitable for low-pressure chemical vapor deposition experiments <1999MI958>. Thestructure of this compound was determined by electron diffraction and density functional theorycalculations <1999JST29>.
6.06.2.1.4 Functions bearing mixed metalloids
There are several methods for the production of compounds of the general structure RC(E1Xm)(E2Xn) (E3Xm�n), where E1, E2, and E3=Si, B, or Ge, but three groups of reactions aremost important: (i) synthesis based on �-silyl-, boryl, or germyl-substituted organometallics;(ii) synthesis based on p�-bonded low-coordinate boron and germanium derivatives; and(iii intermolecular C–H insertions and cyclization reactions involving a stable germylene.
(i) Synthesis based on a-silyl-, boryl-, or germyl-substituted organometallics
This approach has been extensively studied and seems to be most general for preparingfunctions bearing mixed metalloids <1995COFGT(6)171>. An example provided in Equation (8)illustrates the application of this strategy for the synthesis of base-stabilized germylene containing aSi2(GeII)C function <1997OM2116, 1999OM389>.
NLi
TMSTMS
GeCl2.diox
53%
NGe
NTMS
TMS
TMSTMS
Et2O, –78 °Cð8Þ
Wiberg and co-workers have investigated the reaction of (Me3Ge)2CHLi with But2Si(H)F, which givesthe sterically overloaded digermylsilylmethane 78<1996JOM(511)239>. With bromine, 78 reacts, as dohydrosilanes, to form bromosilyl derivative 79. Coupling reaction between 79 andMeLi followed by thetreatment of a lithium intermediate 80 with MeOH lead to the silyldigermylmethane 81 (Scheme 27).
Br
Br Br
GeBr3
Br3Ge GeBr3
GeH3
H3Ge GeH3
3GeBr2.diox
Toluene, 85 °C 89%
LiAlH4
15%
77 76
Scheme 26
Li
Me3Ge GeMe3 12 h, 130 °C 77%
SiMeBut2
Me3Ge GeMe3
Br2
95%
MeLi
THF, –78 °C
MeOH
95%
78 79
80 81
SiMe3Ge
Me3Ge
H
But
But SiMe3Ge
Me3Ge
Br
But
But
SiLi
Me3Ge
Me
But
ButMe3Ge
Bu2SiHFt
CCl4, 0 °C
Scheme 27
Functions Containing at Least One Metalloid (Si, Ge, or B) 221
Silylation of 2-trimethylsilylboratabenzene salt 83 affords compounds 84 and 85 as a slowlyinterconverting equilibrium mixture of isomers (Scheme 28). When this reaction was run in THF,a mixture of the monosilylated compound 82, the expected bis(trimethylsilyl) derivatives, andmore highly silylated species were formed. When pentane was used as the reaction medium, thechemoselectivity was much improved. The product obtained was essentially an equilibriummixture of the isomers 84 and 85 in a 4:3 ratio with some 82 (10–20%) <1997OM926>.
Structurally related 1-chloro-1,2-dihydroborinines 88 and 89 were prepared according to thepathway outlined in Scheme 29. Treatment of stannacyclohexadiene 86 with lithium diisopro-pylamide (LDA) followed by chlorotrimethylsilane affords stannacycle 87 in excellent yield.Transmetallation through reaction of 87 with BCl3 then provides boracyclohexadienes 88 and 89<1997JOC8286>.
(ii) Synthesis based on p�-bonded low-coordinate boron and germanium derivatives
The scope of these reactions is restricted to the preparation of specific polyfunctional compounds.Thus, reaction of methyleneborane 90 with trimethylstannylethyne 91 affords the spiro cycliccompound 92, which upon isomerization followed by rearrangement gave compound 93. Lithiumexchange of the latter with ButLi followed by treatment with chlorotrimethylsilane result inthe formation of the cyclic compound 94 containing an B2SiC function (Scheme 30)<1994AG(E)2064>.
BMe
TMSLDA
THF, 1 h,
92%
BMe
TMSLi TMS–Cl
Pentane, rt
72%
BMe
BMe
TMSTMS
82 83 84 85
+TMS
TMS
Scheme 28
i. LDA
ii.TMS– Cl
90%
BCl3–Bu2SnCl2
55–60%BCl
TMS TMS+
86 87 88 89
BCl
TMS
TMSSnTMS
TMS
Bu BuSnTMS
Bu Bu
Scheme 29
ArMe3Sn
ButLi TMS–Cl
+
Ar = 3,5-But2C6H3, Dur = 2,3,5,6-Me4C6H
90
91
92
93 94
B BDur
TMS
TMS
DurB
BDur
Dur
ArMe3Sn
TMS
TMS
B
BC
TMS
TMS
Dur
Dur
SnMe3
Ar
B
BC
TMS
TMS
Dur
Dur
Li
Ar
B
BC
TMS
TMS
Dur
Dur
TMS
Ar
–20 °C
Scheme 30
222 Functions Containing at Least One Metalloid (Si, Ge, or B)
The tetracoordinate germanium derivative 96 is reported to be formed by intramolecularcyclization of 1-germaallene 95 (Equation (9)) <1998CL811>.
9596
Benzene, 80 °C
Tbt = 2,4,6-[(TMS)2CH]3C6H2
Ge CTbt
TbtGe
H
TMS
TMS
(TMS)2HC
Tbt
CH(TMS)2
ð9Þ
Diels–Alder and ene reactions of the germaethene Me2Ge=C(TMS)2 generated as a reactionintermediate by thermolysis of Me2GeCl-CLi(TMS)2 <1996ZN(B)838> or cycloadduct of thegermaethene and anthracene <2000CJC1412> lead to various cyclic compounds containing anSi2GeC function <1996ZN(B)838>. Similarly, thermolysis of But2SiF-CLi(GeMe3)2 at 100 �C inbenzene and in the presence of propene, isobutene, butadiene, or 2,3-dimethylbutadiene leads toene reaction products and/or [4+2]-cycloadducts of the germaethene Me2Ge=C(GeMe3)(SiMe2Bu
t2) 97 which contain a SiGe2C unit (Scheme 31) <1996JOM(519)107>.
(iii) Intermolecular C�H insertions and cyclization reactions involving a stable germylene
A great deal of chemical research has focused upon C�H and C�Hal insertions and cyclizationreactions involving divalent germylenes in the hope of developing general methods for introducingfunctionality into a variety of organic molecules <1996OM741, 1997AG(E)2514, 1996JOM(521)387,1999JA4229>. BanaszakHoll and co-workers demonstrated that bis[bis(trimethylsilyl)methyl]germy-lene 98 inserts into the �-C�H bond of acetonitrile in the presence of THF and LiCl, MgCl2, or LiBrto yield 99 quantitatively as monitored by nuclear magnetic resonance (NMR) spectroscopy. Similarreactivity was observed for propionitrile, phenyl acetonitrile, and succinonitrile (Scheme 32). Thepresence of THF and specific salts was essential for the insertion reactions. For acetonitrile, noreaction occurred over the period of a week at 20 �C when benzene, diethyl ether, or 1,4-dioxanewere used as solvents in the absence of added salts. However, when 0.5 equiv. of THFwas added to thereaction mixture in benzene, the reaction slowly proceeded to �5% completion after 3 days at 20 �C.The reaction rate was dramatically affected by added salt. In THF solvent, the reaction is completewith 2min and 20min, respectively, if � 0.2 equiv. of MgCl2 or LiCl are added <2001JA982>.
It has also been found that by the reaction of germylene 98 with an excess of trans-1,2-dichloroethene, cis-1,2-dichloroethene, or 1,1-dichloroethene, the [(TMS)2CH]2ClGe-functiona-lized ethenes 100, 102, and 104 can be obtained in quantitative yields <1996JOM(521)387>.The stereochemistry of the starting material was retained in the product, showing that thesereactions proceeded stereospecifically. When 2molar equiv. of 98 were used with 1,2-dichloro-ethenes, the reactions gave the double germylene insertion products 101 and 103 (Scheme 33).
Ge SiMe2ButMeMeGeMe3
GeSiMe2But
GeMe3
Me
Me
GeGe GeMe3
SiMe2But2
MeMe
MeMe
Me3Ge
GeH
GeMe3MeMe SiMe2But
GeH
GeMe3MeMe SiMe2But
97
77%89%
9773%
Bu t2MeSi
Scheme 31
Functions Containing at Least One Metalloid (Si, Ge, or B) 223
A stable digermacyclobutane 106 bearing (TMS)2CH groups at germanium atoms was obtainedby the interaction of 98 with ethylene (Scheme 34). This reaction presumably runs via thegermirane intermediate 105. An attempt to prepare the corresponding digermacyclobutanes bythe reaction between 98 and propene or 2-butene was unsuccessful. Nevertheless, the digermacy-clobutane 106 is a useful synthon for novel organogermanium compounds. For example, photo-lysis of 106 in carbon tetrachloride afforded 1,4-digerma-1,4-dichlorobutane 107 quantitatively,and photolysis in 2,3-dimethylbutadiene yielded 1-germacyclopent-3-ene 108 <1995OM2139>.The photolysis of 106 in a toluene solution of C60 provided the germylene and germacyclopro-pane adducts of C60, respectively. The former is possibly the first example of a closed [6,5]-bridged derivative of germacyclopropane, while the latter is a closed [6,6]-bridged fullerenederivative of germacyclopentane <2001JOM(636)82>.
Heterocyclic GeIV�O species including a conjugated triene system and Si2CHGe functions havebeen obtained from the reaction of 98 with phenones. For example, germylene 98 reacts withbenzophenone in THF at ambient temperature to produce compound 109. A number of otherphenone species yield products similar to 98 and benzophenone. The reaction occurs with bothweakly electron-withdrawing and releasing groups present on the rings. Moreover, the pattern of
Ge
TMSTMS
TMSTMS
GeH
TMSTMS
TMSTMS
PhCH2CNGe
HTMS
TMS
TMSTMS
CNCNPh
GeH
TMSTMS
TMSTMS
CNGe
HTMS
TMS
TMSTMS
CNCN Me
MeCN
MeCH2CNNC(CH2)2CN98 99
Scheme 32
Cl
Cl R2Ge
rt
R2Ge
Reflux
Cl
Cl
100 101
102 103
104
R = CH(TMS)2
Cl Cl Cl GeCl
TMSTMSTMS
TMS
Ge Ge
TMS
TMSTMS
TMS
Cl Cl
TMS
TMSTMS
TMS
Ge
Cl
TMSTMSClTMS
TMS
Ge
Ge
TMSTMSClTMS
TMSCl
TMS
TMS
TMSTMS
R2Ge
Reflux
R2Ge
rt
R2Ge
rtGe
Cl
TMSTMSTMS
TMS
Scheme 33
224 Functions Containing at Least One Metalloid (Si, Ge, or B)
reactivity of the 4,40-dichlorobenzophenone and benzophenone imine resembles that of thebenzophenone. In each case, rather than undergoing insertion, the germylene instead exclusivelyactivates the aromatic ring, forming compounds 110 and 111 (Scheme 35) <2002OM457>.
(iv) Miscellaneous
The exhaustive hydroboration of the (C�C)-groups in dimethyl-di-1-propynylsilane by addingEt2BH at room temperature is presumed to lead initially to the formation of a mixture of thethreo- and erythro-3,3,5,6-tetrakis(diethylboryl)-4,4-dimethyl-4-silaheptanes 112. The erythro-112reacts further by borane catalyzed intermolecular condensation to substituted disilatetraboratri-cyclo[6.2.16,9]dodecane 113. In contrast, the erythro-112 undergoes intramolecular, thermal elim-ination of Et3B to give the 1,2-diethyl-2,4-bis(diethylboryl)-3,3,5-trimethyl-3-silaborolane 114(Scheme 36) <1995ZN(B)439>.
Thermolysis of the silole 115 in a sealed evacuated tube without solvent at 175 �C quickly andquantitatively resulted in the formation of the 2,4-disila-1-germatricyclo[2.1.0.02.5]pentane 116.The tricyclic skeleton of 116 incorporates the two fused three-membered ring comprising alldifferent group 14 elements: C, Si, and Ge (Equation (10)) <2002JA9962>.
+
98105
106
98
106CCl4
hνhν–H2C=CH2
107 108
H
H
H
HGe
TMSTMS
TMSTMS
Ge TMS
TMS
TMS
TMS
Ge GeTMS
TMS
TMSTMS
TMSTMS
TMS
TMS
Ge TMS
TMS
TMS
TMS
GeGe
Cl
Cl
TMS
TMS
TMSTMS
TMSTMS
TMS
TMS
Scheme 34
Ge
TMSTMS
TMSTMS
PhC(=NH)Ph
PhCOPh
CO
ClCl
OGeTMS
TMSTMS TMS
Ph
NHGeTMS
TMSTMS TMS
Ph
OGeTMS
TMSTMS TMS
Cl
Cl
98 109
110111
Scheme 35
Functions Containing at Least One Metalloid (Si, Ge, or B) 225
SiSi
Ge
R
R Ph
R R
R = ButMe2Si
115 116
Si
Ge
SiR
R Ph
R H
R175 °C, 10 mm
ð10Þ
6.06.2.2 Functions Containing Metalloids and Metals
The work on functions RC(EXm)n(MLk)3�n (E=Si, Ge, or B; M=metal; R=H or organyl;X=any substituent; n=1 or 2) up to 1994 has been reviewed <1995COFGT(6)171>, and anaccount up to 1996 on compounds of elements of groups 11–13 containing (TMS)3C, (PhMe2Si)3C,and related ligands can be found <1996CCR125>. A review of the synthesis and reactions ofcompounds [(TMS)2CH]2E-E[CH(TMS)2]2 (E=Al, Ga, or In) contains much that is relevant tothis chapter <1997CCR1>. Thus, this section considers in general, besides a number of funda-mentals, the literature for 1997–2003.
6.06.2.2.1 Functions bearing silicon(s) and metal(s)
Synthesis of compounds of the general formula RC(SiX3)n(MLk)3�n, where n=2 or 1, is made byone of the following methods, which are mainly based on the standard synthetic proceduresdeveloped for the preparation of organometallic species: (i) metal–hydrogen exchange reactions ofsilylmethanes with basic metal-containing reagents; (ii) metal–halogen exchange reactions oroxidative metallation of halo(silyl)methanes; (iii) organometallic addition to vinyl silanes; (iv)synthesis via (cyclo)addition to stannaethenes; and (v) transmetallation of an already �-metalatedorganosilanes. Most of the work in the decade 1993–2003 in this area has centered on thesynthesis of specific organometallic derivatives, often with the goal of preparing new kineticallystabilized species.
SiMeMe
MeMe Me
H BEt2SiMe2R
HEt2BMe
Et2B HSiMe2R
HEt2B
BH BH
B
SiMeMe
BEt2
EtMe
Et2B
H
EtH
BB
BB
Si
Si
EtEt
MeMe
Me Me
Et
EtEt
Et
H
H
Me
H
Me
H
threo -112 erythro -112
+
113 114
–4Et3B
R = Et(Et2B)2C
–Et3B
Scheme 36
226 Functions Containing at Least One Metalloid (Si, Ge, or B)
(i) Metal–hydrogen exchange
In order to assess the potential utility of various possible metallating reagents, Seyferth andLang carried out studies of the metallation of Me3SiCH2SiMe3, (Me3SiCH2)2SiMe2, (Me3Si)2CHSi-Me2CH2SiMe3, and cyclo-(Me2SiCH2)3, using several strong organometallic bases such asButLi/TMEDA, BusLi/TMEDA, BunLi/ButOK, and BunLi/ButOK/TMEDA <1991OM551>.BunLi/ButOK was found to be the most effective metallation reagent for CH2 groups in anSiCH2Si environment. The yields of monolithium derivatives in these reactions are very good,but further metallation did not occur even when a fivefold excess of the reagent was used.
The bis(triethoxysilyl)methyl lithium 117 is simply prepared by treatment with t-butyllithium ofthe corresponding disilylmethane (Equation (11)). This compound is a very convenient startingmaterial for a variety of common disilylmethane derivatives <1998JOM(562)79>.
ButLi
117
LiSi(OEt)3
Si(OEt)3
Si(OEt)3
Si(OEt)3
THF, –65 °C ð11Þ
The 1,8-silanonaphthalene 118 has been used to generate uniquely the lithiodisilylmethane 120as indicated in Scheme 37. The addition of MeLi to 118 presumably affords ring-opened1-(8-silylnaphthyl)lithium 119, which undergoes proton migration leading to 120, a useful anionsynthon <2000OM5582>.
Lithiation of 2-[bis(trimethylsilyl)methyl]-6-methylpyridine with n-butyllithium yields lithiocar-banion 121, which reacts readily with chlorosilanes such as HSiCl3, MeSiCl3, Me2SiCl2, andMe3SiCl to form the corresponding hypervalent five-coordinate silicon species 122 (Scheme 38)<2000OM4437>.
(ii) Metal–halogen exchange
Bis(dimethylphenylsilyl)bromomethane, (Me2PhSi)2HCBr, has been reported to react withn-butyllithium in ether to give (Me2PhSi)2HCLi. The compound was isolated as solvent-freecrystals and studied by multinuclear NMR and X-ray crystallography <1997OM4728>.
MeLiTHF, rt
TMS–Cl46%
118119
120
Si TMSTMS SiTMS
TMS
LiMe
SiMe
TMS
Li
TMS
SiMe
TMS
TMS
TMS
Scheme 37
NMeTMS
TMS
BunLi
THF, 0 °CXYZSi–Cl
121
122a–d
a, X = H, Y = Z = Cl (79%)
b, X = Me,Y = Z = Cl (72%)
c, X = Y = Me, Z = Cl (94%)
d, X = Y = Z = Me (78%)
NMeTMS
LiTMS
NMe
Si
Z
YX
TMS
TMS
–78 °C
Scheme 38
Functions Containing at Least One Metalloid (Si, Ge, or B) 227
By analogy with the preparation of bis(iodozincio)methane from diodomethane and zinc, thereaction of silyl-substituted dibromomethanes, RMe2SiCHBr2 (R=Me, Ph, p-MeOC6H4), withzinc dust in the presence of a catalytic amount of lead in THF provides route to silyl-substitutedbis(bromozincio)methanes, RMe2CH(ZnBr)2 (72–80% yield) <1998SL1315>.
Yet another example of the diversity of the original reagents, which may be used to synthesizelithiodisilylmethanes by metal–halogen reactions is the interaction of polysilacyclohexanes con-taining pseudohalogen (PhS) groups with lithio radical anion (see Schemes 14 and 16)<2000JOM(611)12>.
(iii) Organometallic addition to vinyl silanes
The reactivity of 1,1-bis(trimethylsilyl)ethane 123 toward lithium metal has been re-investigated byMaercker and co-workers <1998EJO1455>. In THF, the exclusive formation of the product ofreductive dimerization 124 was observed. When hexane or diethyl ether was used as solvent, analmost quantitative yield of a 1:1 mixture of the two lithio derivatives 124 and 126 was isolated.Lithium hydride elimination from the 1,4-dilithioalkane 124 can be ruled out since mixtures of 124and 126, once synthesized, were found to be stable. Presumably, 123 adds to 125, which may begenerated as a by-product, with formation of 126. In contrast to 123, 1,1-bis(trimethylsilyl)-3,3-dimethyl-1-butene 127a reacted with lithium metal to give the 1,1-bis(trimethylsilyl)-1,2-dilithio-alkane 128a, which shows no tendency to form a dimer product. The general reaction pathway wasthe same when the t-butyl group at the �-position was replaced with a phenyl group (Scheme 39).
(iv) Synthesis via (cyclo)addition to stannaethenes
The scope of these reactions, being investigated mainly by Wiberg and co-workers, has not yetbeen well delineated. Even so, the following useful procedures have been developed.
Lithium organils (RLi) act as very active trapping reagents for Me2Sn=C(TMS)2 with for-mation of the adducts Me2Sn(R)-C(Li)(TMS)2. The insertion reactivity of RLi decreases when thebulkiness of R increases (decreasing reactivity in the order MeLi>BunLi>PhLi>ButLi;MeLi>(TMS)2CHLi>(TMS)3CLi). The influence of electronic effects is obviously smaller than
123124
125 126
127a 128a
127b 128b
2Li
123
2Li
THF
THF
Hexane or Et2O –LiH
R = But (a), Ph (b)
Li
TMSTMS
TMS
LiTMS
TMS
TMS
TMS
TMS
LiTMS
TMSTMS
LiTMS
TMS
TMS
R Li
TMS
Li
RTMS
2Li
–LiH
Scheme 39
228 Functions Containing at Least One Metalloid (Si, Ge, or B)
those of steric effects (decreasing reactivity in the order (TMS)2(Me2ClSi)CLi>(TMS)2(Me2Br-Si)CLi>(TMS)3CLi) <2000JOM(598)292>.
Reactions of the stannaethene 129 with butadiene and propene as well as their methyl andphenyl derivatives afford Diels–Alder adducts and ene products containing an SnC(TMS)2 unit(Scheme 40). The reactions are accelerated by an increasing tendency of substituents in butadieneor propene to donate electrons and retarded by increasing bulkiness of substituents in 1,4- or 1,3-positions. It is concluded that Diels–Alder and ene reactions of 129 occur in a concerted way andare orbital controlled <1998CEJ2571, 2000CJC1412>.
(v) Transmetallation reactions
A convenient route to bis(trimethylsilyl)methyl-substituted organoaluminum compounds is viatransmetallation reactions starting from [(TMS)2CH]2Zn and aluminum halides. For example,compound 130 was prepared in high yield from the reaction depicted in Scheme 41. Compound130 was reacted with Na/K alloy, which results immediately in the formation of organoalanes 131and 132 due to a disproportion reaction <2001MI225>.
The alkyl transferring properties of [(TMS)2CH]2Zn toward transition metal halides have alsobeen studied. The monosubstituted tantalum halides, (TMS)2CHTaX4 (X=Cl, Br), wereprepared by the reaction of TaX5 with [(TMS)2CH]2Zn in hexane <1999OM832>. Compounds
SnTMS
TMS
Me
Me
SnMe
TMSTMS
Me
SnMe
MeTMS
TMS
SnMe
TMSTMS
Me
SnMe
Me TMS
TMS
+
84:16
100 °C, 2 days
100 °C, 3 days
100 °C, 2 days
129
Scheme 40
ZnTMS
TMS
TMS
TMS+ 2AlCl3
Al
TMS TMS
TMS
TMSTMS
TMS + AlCl
ClCl
TMSTMS K
+ Al
Hexane, rt, 48 h
72%
130
Na /K
131 132
AlCl
AlCl
TMSTMS
TMSTMS
Cl
Cl
Scheme 41
Functions Containing at Least One Metalloid (Si, Ge, or B) 229
(TMS)2CHTiCl3, (TMS)2CHNbCl4, and (TMS)2CHNbBr4 have been isolated, respectively, fromreacting TiCl4, NbCl5, and NbBr5. In addition, the fluoride derivative (TMS)2CHNbF4 wasprepared via chlorine–fluorine metathesis employing Me3SnF as a fluorinating reagent. Thecrystal structure of (TMS)2CHNbCl4 was determined by single-crystal X-ray diffraction<2001JOM(621)310>.
The first bis(trimethylsilyl)methyl-substituted organogallium compound containing a Ga�Gasingle bond, 133, was synthesized by Uhl and co-workers according to Scheme 42<1989JOM(364)289>. Remarkably, this compound reacted with tropolone by replacement of two(TMS)2CH groups and retention of its Ga�Ga single bond <2002ZN(B)141>. As a starting com-pound for the synthesis of an alkylgallium-bridged [1,1]-ferrocenophane 135 Uhl and co-workersemployed the trichloroalkylgallate 134, which is easily available by the reaction of GaCl3 with(TMS)2CHLi in THF (Scheme 43). Treatment of the adduct 134 with 1,10-dilithioferrocene in hexaneafforded the orange-red compound 135 in 47% yield <2001JOM(637/639)300>.
The transmetallation of the bridged ditin compound 136 with (TMS)2CHLi afforded a neworganotin derivative 137, which was converted into its tetrachloro derivative 138 by stepwisereaction with Me2SnCl2 and SnCl4 (Scheme 44) <1998OM4096>. Along with this, the di- andtrimethylene-bridged ditin compounds, 140 and 141, were prepared by reaction of 139 with(TMS)2CHLi followed by treatment with mercuric chloride (Scheme 45) <1998OM4096>.
The synthetic potential of lithium bis(trimethylsilyl)methanide in transmetallation reactions isalso illustrated by the synthesis of electron-deficient monocyclopentadienylvanadium(III) dialkyl142 <1993OM2268> and vanadium(III) hydrocarbyl 143 <1999JCS(D)3345> (Equations (12)and (13)). These results provide a further demonstration that the bulky (TMS)2CH ligand maystabilize unusual metal complexes.
Ga2Br4.2 diox +
Li
TMS TMS
O
OH
133
Pentane, –70 °C 83%
Ga GaO
OO
O
TMSTMS
TMSTMS
Ga GaTMS
TMS
TMS
TMSTMS
TMSTMS
TMS
Scheme 42
GaCl3 + (TMS)2CHLi [Cl3Ga-CH(TMS)2] [Li(THF)]
62%134
Fe[CpLi(TMEDA)]2
135
Fe
Ga
Ga
Fe
TMS TMS
TMS TMS
THF/Et2O, –10 °C
THF, –80 °C
Scheme 43
230 Functions Containing at Least One Metalloid (Si, Ge, or B)
CpVCl2(PMe3)2 + 2 (TMS)2CHLi
90% 142
VTMS
TMS
TMS
TMSEt2O, 0 °Cð12Þ
+ 2Li
TMS TMS
60%
Cl
ClV V
N
N N
NTMS
TMSTMS N
TMS NTMS
TMS
VN
N
TMS
TMS NTMS
TMS
TMS
143
Toluene, –78 °C ð13Þ
Neutral alkyl derivative lanthanides, stabilized by bis(trimethylsilyl)groups, are, of course,known and interpretation of their stability in terms of steric protection appears to be generallyaccepted <1994CC2691, 1995JCS(D)3933>. Alkyl lanthanide complexes are the precursors oforganolanthanide hydrides by hydrogenolysis of the lanthanide�carbon �-bond. Bis(trimethylsi-lyl)methyl lanthanides are especially often used because they are usually hydrocarbon-solubleunsolvated species that can be straightforwardly obtained by reaction of organolanthanide halideswith (TMS)2CHLi. The synthesis of 146 and 147 illustrates this. The crude products from thereaction of [LnCl3(THF)x] (Ln=Nd, Sm) with 2,3,4,5-tetramethylphospholylpotassium, 144 and145, reacted smoothly with (TMS)2CHLi to give bis(trimethylsilyl)methyl derivatives 146 and 147in fair-to-good yields (Scheme 46). [(C4Me4P)2LaCH(TMS)2] was also obtained by the sameprocedure, but the yields were very low and inconsistent <1999EJI1041>.
Lanthanide metallocene cation [(C5Me5)2Sm][BPh4], which may be prepared from (C5Me5)2Smand AgBPh4, reacts with (TMS)2CHLi in benzene to produce (C5Me5)2SmCH(TMS)2 in over96% yield. [(C5Me5)2Nd][BPh4] similarly reacts with (TMS)2CHLi to produce(C5Me5)2NdCH(TMS)2 in quantitative yield <1998JA6745>.
2(TMS)2CHLi
Pentane, 20 °C 82%
2Me2SnCl2
110–120 °C, 30 h
SnCl4
60–70 °C, 12 h
74%
136 137
138
Sn SnMe
Me Me
MeCl
Me
MeCl Sn Sn
Me
Me Me
Me
Me
Me
TMS
TMS
TMS
TMS
Sn SnMe
Me TMS
TMSCl
Me
TMS
TMS
Cl
Me
Sn SnMe
Me TMS
TMSCl
Cl
TMS
TMS
Cl
Cl
Scheme 44
2(TMS)2CHLi
Pentane, 20 °C
4HgCl2
139
140 141
X = (CH2)n; n = 2 or 3
73–87%X
SnPh2
SnPh2
F
F
XSnPh2
SnPh2
TMSTMS
TMSTMS
XSnCl2
SnCl2
TMSTMS
TMSTMS
Scheme 45
Functions Containing at Least One Metalloid (Si, Ge, or B) 231
6.06.2.2.2 Functions bearing boron(s) and metal(s)
Important methods for the preparation of polyheteroatom species of the general formulaRC(BX2)n(MLm)3�n, where n=1 or 2, M is metal, and R=H, alkyl, or aryl, along with somerepresentatives examples, are summarized in Scheme 47. These comprise reactions: (i) via metal–hydrogen exchange (deprotonation of diorganoboranes and related compounds); (ii) via transmetal-lation; (iii) via cleavage of 1,1-diboryl- and 1,1,1-triboryl compounds; and (iv) via addition to vinylboranes and methyleneboranes.
During the years from the publication of chapter 6.06, COFGT (1995) to the end of 2003, littlefurther effort was given to expanding this chemistry. Readers are referred to the reference<1995COFGT(6)171> and review <1991COS(1)487> for more detailed information concerningsynthetic potential of the mentioned methods.
A unique method for the synthesis of compounds containing a BSn2C function utilizes the reactionof the bicyclic N-pyrrolylborane 148 with bis(trimethylstannyl)ethyne <1997JOM(545/546)297>.The interaction of 148 with 2 equiv. of Me3SnC�CSnMe3 proceeds selectively to give 149, in whichthe five-membered ring in 148 has been extended by two carbon atoms (Scheme 48).
6.06.2.2.3 Functions bearing germanium(s) and metal(s)
In contrast to the numerous reactions involving metallation of CH2 groups in an SiCH2Sienvironment, the metal–hydrogen exchange reactions have met with very limited success whenapplied to the corresponding germyl analogs <1995COFGT(6)171>.
The metal–halogen exchange reactions seem to be less limited than the direct metallation oforganogermanes. Thus, Wiberg and co-workers have described an efficient route to lithiumbis(trimethylgermyl)methide 151 starting from bromoform (Scheme 49). This approach permitsaccess to bis(trimethylgermyl)bromomethane 150, which is difficult to obtain by other methodsand produces salt-free reagent 151 in good yield. The ease with which the latter is prepared makesit a particularly attractive starting material for a variety of organic and inorganic applications.The reactivity of 151 appears roughly comparable to that of (TMS)2CHLi <1996JOM(511)239>.
Triethylgermyl-substituted bis(bromozincio)methane, Et3GeCH(ZnBr)2, has been preparedfrom the corresponding dibromide by Pb-catalyzed reaction with zinc dust in THF (30–40%yield) <2000SL495>.
6.06.2.2.4 Functions bearing mixed metalloid(s) and metal(s)
Very few species with this special ligand arrangement around the carbon atom have been reportedup to the end of 2003. In practice, they can be prepared by multiple-step procedures involvingreactions described in Sections 6.06.2.2.1–6.06.2.2.3. In particular, if mixed compounds such asXnE
1CH2E2Ym or XnE
1CH(Hal)E2Ym are available then metal–hydrogen or metal–halogenexchange reactions seem to be the most practical route to metallated derivatives. Anotherattractive and potentially general route to functions with mixed metalloid(s) and metal(s) isprovided by the reactions of heteroalkenes with organometallics. Some examples taken fromthe literature are illustrated by Equations (14)–(17).
[LnCl3(THF)x]2C4Me4PK
THF/Et2O[(C4Me4P)2LnCl2K]
(TMS)2CHLi
53–67%
144, Ln = Sm
145, Ln = Nd
146, Ln = Sm
147, Ln = Nd
LnTMS
TMS
P
P
Scheme 46
232 Functions Containing at Least One Metalloid (Si, Ge, or B)
Mes2B BMes2KH
THF
B
B BO
O O
O
OO
Li
B BO
O O
OPh3PbCl
MeLi
SnPh3
B BO
O O
OMeLi
But
Cl
ButClTMS
TMS
THF
C BMes
TMSTMSMes
Li+
B C BBut
MesMes
But
SnPh3
B LiO
O
Mes2B BMes2
K
Li
B BO
O O
O
PbPh3
B BO
O O
O
TMSTMS
K K
But
But
2Li+
Li
B BBut
Mes
But
Mes
Approaches to Forming Stable RC(BX2)n(MLm)3–n Species
Via metal–hydrogen exchange
Via transmetallation reaction
THF/ether
Via cleavage of 1,1-diboryl- or 1,1,1-triboryl compounds
THF, –70 °C
THF, –78 °C
Via addition to vinylboranes and methyleneboranes
K /Na
2ButLi – – CpH
<1982JCR(S)132>
<1976JOM(110)25
<1976JOM(110)25>
<1973JA5096>
<1985AG(E)788>
<1988AG(E)1370>
Scheme 47
Functions Containing at Least One Metalloid (Si, Ge, or B) 233
Si GeMe3But
But
H
Si GeMe3But
But
H
LiMeLi
THF
<1996JOM(511)239>
ð14Þ
TMS BO
O LiTMPTHF
TMS B
O
OLi
<1983OM230, 1991COS(1)487>
ð15Þ
B TMSMe
Me3SnCl Li+
BMe
TMS BMe
Me3Sn TMS
–+
<1997OM926>
Pentane, rt
SnMe3
ð16Þ
<1987JA931, 1991COS(1)487>
RM R M
TMSBMes2
TMS
BMes2
R = Bun, But, Ph, (R1S)2CH, ButO2CCH2, CH2=CH(CH2)4, BunCu(CN)2
ð17Þ
NB
Et
Me3SnC SnMe3
BEt
SnMe3
SnMe3SnMe3
Me3Sn
BEt
Me3Sn SnMe3
BEt
SnMe3Me3Sn
SnMe3
Me3Sn
Me3SnC SnMe3
148
149
C6D6, rt
Scheme 48
Br
Br Br
Br
Me3Ge GeMe3
Li
GeMe3Me3Ge
Me3GeCl, 2BunLi
THF, –78 °C 85%
BunLi
150 151
Et2O, –78 °C
Scheme 49
234 Functions Containing at Least One Metalloid (Si, Ge, or B)
6.06.3 FUNCTIONS CONTAINING THREE METALS
In contrast to sp2- <2000CRV2887> and sp3-1,1-bismetallic derivatives <1996CRV3241>, whichhave been intensively studied in the late 1990s and early 2000s, the chemistry of functionsRC(MLk)(M
1Ll) (M2Lm) (M, M1, M2=metal) featuring three �-bonds between carbon and metal
atoms is in its infancy. Although several structural types of sp3-geminated trismetallics are known,information about these compounds remains sparse. Little further effort has been given to expandingthis chemistry since the publication of COFGT (1995). This chapter therefore presents an illustrativesummary of the methods used for the preparation of 1,1,1-trismetallic derivatives. Methods forpreparing specific types of compounds were discussed previously <1995COFGT(6)171>.
6.06.3.1 Three Similar Metals
Isolable compounds of the type RC(MLm)3 (M=metal) are known with M=Li, Hg, Al, Sn, andPb. Table 1 outlines the synthetic approaches to these species with an example from each majormethod. The limits of the methods have certainly not been fully explored and, up to the end of2003, comparatively little has been published on work devoted to the use of trimetallomethanes asreagents for organic synthesis.
The following tentative generalizations may be useful.(i) Direct halogen–metal exchange in polyhaloalkanes by treatment with reactive metal, such as
Li or Mg, is only of limited value for the preparation of polymetalated methanes due to�-elimination of metal halide after the first step being faster than the halogen–metal exchange.However, these difficulties can be overcome by high-temperature reaction of polyhaloalkanes with
Table 1 Preparation of organometallic species of the type RC(MLm)3
Method Description General equation
Preparationequationnumber
From halides:1 Reductive
metallationwith lithiumvapor
RCX3 + 6Li ! RCLi3 + 3LiX (18)
2 Reductivedisplacementof halogen bymetallate anions
RCX3 + 3ML�m ! 3RC(MLm)3 +3X� (19)
From activeC–H compounds:
3 Lithium–hydrogenexchange
FG-RCH3 + 3MR1 ! FG-RCLi3 +3R1H (20)
4 Electrophilicmercuration
FG-RCH3 + HgX2 ! FG-RC(HgX)3 + 3HX (21)
From unsaturatedcompounds:
5 Hydrometallation(M=Al, Sn) + 3MH
M
MM
(22), (23)
Fromorganometallics:
6 Oxidative–reductivetransmetallation
RCM3 + 3M1 ! RCM13 + 3M (24)
7 Boron–mercuryexchange
RC(BX2)3 + 3HgY2 ! RC(HgY)3 +3BX2Y (25)
8 Pyrolysis reactions CHnLi4�n ! CHLi3 + � � � (n=0–3) (26)
Functions Containing at Least One Metalloid (Si, Ge, or B) 235
metal vapor (the Lagow procedure). This technique is especially suited for the preparation oforganometallics of readily ionizable metals (Equation (18)).
Cl
Cl Cl+ 6Li(g)
Li
Li Li+ Li Li
LiLi Li
Li
Li Li+ +
16% 40% 20%
19%
<1983JOM(249)1>
750 °Cð18Þ
(ii) The coupling reactions between chloroform and organostannyl- and organoplumbylmetal-lic compounds of the type R3MLi is the valuable route to the corresponding trimetallomethanes(Equation (19)). It is known that the metallate anions containing transition metals are among thestrongest nucleophiles known to chemists. However, the synthetic potential of reactions betweenpolyhaloalkanes and metallate anions of transition metals is not clear.
Cl
Cl Cl
PbPh3
Ph3Pb PbPh3
Ph3PbLi
91%
<1985CB380>
THF, –60 °C ð19Þ
(iii) Much more easily accessible than the 1,1,1-trilithioalkanes are certain perlithioalkynes, forexample perlithiopropyne (C3Li4), since alkyllithium reagents can abstract quantitatively not onlythe hydrogen atoms on sp-hybridized carbon atom, but also those of the adjacent methyl group(Equation (20)). Unlike alkynes, linear and branched alkenes upon treatment with organolithiumreagents form only mono- and dilithiated derivatives. Typical saturated hydrocarbons are not acidicenough to form the polylithiated species by metal–hydrogen exchange with basic reagents.
LiLi
LiLi
4BunLiHexane
75%
<1984AG(E)995>
ð20Þ
(iv) Metal–hydrogen exchange with Lewis acidic reagents, such as Hg(OAc)2, represents one ofthe most direct and convenient routes to 1,1,1-trimercurioalkane derivatives (Equation (21)). Themethod tends to fail, however, in cases where the C�H bonds are not sufficiently acidic.
<1974JPR557>
MeCN NCHgOAc
HgOAcHgOAc
Hg(OAc)2
93%
150 °C, 20 h ð21Þ
(v) The best way to 1,1,1-trialuminioalkanes involves bishydroalumination of alkynylalanesderived from the reaction of alkali metal acetylides with dialkylaluminum chlorides (Equation (22)).
Bun AlEt2
<1963BSF1462>
AlEt2
AlEt2AlEt2
Bun70 °C
2Et2AlH
ð22Þ
236 Functions Containing at Least One Metalloid (Si, Ge, or B)
(vi) Transmetallation reactions with other elements of the periodic table for example boron/mercury exchange (Equation (23)) can also be used for the synthesis of sp3 geminated trismetallicsbut the limits of the method have not been fully explored.
B(OMe)2
(MeO)2B B(OMe)2 THF, rt 62%
HgCl
ClHg HgCl
<1983JOM(243)245>
3HgCl2
ð23Þ
(vii) A general route to 1,1,1-tristannylalkanes involves the hydrostannation of 1,1-distannyl-1-alkenes (Equation (24)).
R = Me, Bun, Ph, PhCH2, MeOCH2, PhOCH2, PhO
Me3SnH
52–80%
<1985OM1044>
SnMe3
SnMe3SnMe3
RSnMe3
SnMe3
Rð24Þ
(viii) In practice, mercury–lithium exchange reactions represent one of the most effective routesto the trilithiomethanes (Equation (25)). Reactions using tin–lithium exchange would be evenbetter than mercury–lithium exchange, but tris(trimethylstannyl)methanes are not easily available.
HgCl
ClHg HgClLi
Li
Li Li
<1982MI47>
THF, 20 °C ð25Þ
(ix) As a preparative method to be used in practical organic synthesis, pyrolysis reactions donot yet provide advantages over conventional methods. It shows high promise, however, as amethod for preparing otherwise inaccessible species (Equation (26)).
CLi4
<1985JA5313>
8 minCLi4 + C3Li4 + C2Li4 + C2Li2
20% 40% 30% 10%
225 °C
ð26Þ
6.06.3.2 Three Dissimilar Metals
A few of the compounds of the general formula HC(MLk)2(M1Lm) have been prepared
by metallation or transmetallation reactions and examples are described in COFGT (1995)<1995COFGT(6)171>. The readily available trismetallics 152–155 <1983IZV636,1980TCC109> may prove useful in the synthesis of other compounds having three dissimilarmetals bonded to the same carbon; however, the synthetic potential of these species in transme-tallation reactions remains unexplored.
Li
Ph3Sn SnPh3
Li
Ph3Pb PbPh3
SnMe3
Ph3Pb PbPh3 AlEt2
AlEt2AlEt2
152 153 154 155
Functions Containing at Least One Metalloid (Si, Ge, or B) 237
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240 Functions Containing at Least One Metalloid (Si, Ge, or B)
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Functions Containing at Least One Metalloid (Si, Ge, or B) 241
Biographical sketch
Vadim D. Romanenko was born in Lugansk,Ukraine, in 1946. He studied at the Instituteof Chemical Technology, Dnepropetrovsk,Ukraine and received his Ph.D. degree thereunder the direction of Professor S. I. Burmis-trov. Since 1975 he has been working at theNational Academy of Sciences of Ukrainefrom which he earned his Doctor of Chemis-try degree in 1988. He became a full professorin 1991. He has been a visiting scientist at theCentre of Molecular and MacromolecularStudies, Lodz, Poland, the Shanghai Instituteof Organic Chemistry, China, the Universityof Pau & des Pays de l’Adour, France, theUniversity Paul Sabatier, Toulouse, France,the University California Riverside, USA.His research interests include a wide rangeof topics at the border between organic andinorganic chemistry, in particular the chemis-try of multiple bonded heavy main groupelements. He is the author of approximately260 papers on organoelement chemistry. He isalso author of numerous reviews and twomonographs on low-coordinated phosphoruscompounds.
Valentyn Rudzevich was born in Kazatin,Ukraine, in 1968. He received his Diplomadegree in 1992 from Taras Shevchenko KievState University, Ukraine. Since 1992 he hasbeen working at the Institute of OrganicChemistry of National Academy of Scienceof Ukraine, from which he received hisPh.D. degree under the supervision of Profes-sor V. D. Romanenko in 1997. Afterwards, hecarried out postdoctoral studies at the Uni-versite Paul Sabatier, Toulouse, France, Uni-versity of California Riverside, USA and theJohannes Gutenberg University, Germany.On his return to Kiev, he joined the Instituteof Organic Chemistry where he is presentlya Scientist Researcher. His research interestsare focused on organoelement compounds,short-lived intermediates, and coordinationchemistry.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 205–242
242 Functions Containing at Least One Metalloid (Si, Ge, or B)
6.07
Functions Containing Four Halogens
or Three Halogens and One Other
Heteroatom Substituent
A. SENNING and J. Ø. MADSEN
Technical University of Denmark, Kgs. Lyngby, Denmark
6.07.1 TETRAHALOMETHANES, C(Hal)4 2446.07.1.1 Four Similar Halogens 2446.07.1.1.1 Tetrafluoromethane 2446.07.1.1.2 Tetrachloromethane 2446.07.1.1.3 Tetrabromomethane 2446.07.1.1.4 Tetraiodomethane 244
6.07.1.2 Three Similar Halogens and One Different Halogen 2446.07.1.2.1 Trifluoromethyl halides 2446.07.1.2.2 Trichloromethyl halides 2456.07.1.2.3 Tribromomethyl halides 2456.07.1.2.4 Triiodomethyl halides 246
6.07.1.3 Two Similar Halogens 2466.07.1.3.1 Difluoromethylene dihalides 2466.07.1.3.2 Dichloromethylene dihalides 2466.07.1.3.3 Dibromomethylene dihalides 2476.07.1.3.4 Diiodomethylene dihalides 247
6.07.1.4 Bromochlorofluoroiodomethane 2486.07.2 METHANES BEARING THREE HALOGENS 2486.07.2.1 Three Halogens and a Chalcogen 2486.07.2.1.1 Three halogens and an oxygen function 2486.07.2.1.2 Three halogens and a sulfur function 2516.07.2.1.3 Three halogens and an Se or Te function 257
6.07.2.2 Three Halogens and a Group 15 Element 2586.07.2.2.1 Three halogens and a nitrogen function 2586.07.2.2.2 Three halogens and a phosphorus function 2606.07.2.2.3 Three halogens and an As, Sb, or Bi function 261
6.07.2.3 Three Halogens and a Metalloid 2616.07.2.3.1 Three halogens and a silicon function 2616.07.2.3.2 Three halogens and a boron function 2626.07.2.3.3 Three halogens and a germanium function 262
6.07.2.4 Three Halogens and a Metal Function 2636.07.2.4.1 Trihalomethyl alkali and earth alkali metals, CHal3M (M=Li, Na, K, Cs, Mg) 2636.07.2.4.2 (Trihalomethyl)aluminum, -gallium, -indium, and -thallium compounds, CHal3MRn
(M=Al, Ga, In, Tl) 2636.07.2.4.3 (Trihalomethyl)tin and -lead compounds, CHal3MRn (M=Sn(II), Sn(IV), Pb(IV)) 2636.07.2.4.4 (Trihalomethyl)zinc, -cadmium, and -mercury compounds, CHal3MR (M=Zn,
Cd,Hg(II)) 2636.07.2.4.5 (Trihalomethyl)copper, -silver, and -gold compounds, CHal3MRn (M=Cu(I), Cu(III),
Ag(I), Ag(III), Au(I), Au(III)) 2646.07.2.4.6 Miscellaneous trihalomethyl transition metal compounds, CHal3MRn (M=transition
metal) 264
243
6.07.1 TETRAHALOMETHANES, C(Hal)4
6.07.1.1 Four Similar Halogens
All four compounds CF4, CCl4, CBr4, and CI4 are commercially available.
6.07.1.1.1 Tetrafluoromethane
Two Russian patents deal with the industrial preparation of CF4 by fluorination of activatedcarbon <2002RUP2181351> and of trifluoromethane <2002RUP2181352> with F2. Accordingto a US patent, CF4 can be prepared by vapor-phase chlorofluorination of methane with Cl2 andHF in the presence of a catalyst such as CrO3 <1995USP5446218>. A similar process (fixed-bedreactor, reaction temperature 449 �C) with trichloromethane as the starting material yields CF4
with 99.8% conversion and 29.1% selectivity <1997JAP09020695>.
6.07.1.1.2 Tetrachloromethane
The formation of CCl4 by chlorination of methane with Cl2 is catalyzed by nanocrystalline MgOor nanocrystalline CaO <2000JA5587>.
6.07.1.1.3 Tetrabromomethane
No further advances have occurred in this area since the publication of chapter 6.07.1.1.3 in<1995COFGT(6)211>.
6.07.1.1.4 Tetraiodomethane
No further advances have occurred in this area since the publication of chapter 6.07.1.1.4 in<1995COFGT(6)211>.
6.07.1.2 Three Similar Halogens and One Different Halogen
6.07.1.2.1 Trifluoromethyl halides
(i) Chlorotrifluoromethane
According to a US patent, the commercially available CClF3 is one of the products of the vapor-phase chlorofluorination of methane with Cl2 and HF in the presence of a catalyst such as CrO3
<1995USP5446218>.
(ii) Bromotrifluoromethane
The boiling point of CBrF3 is 59.0�C <2001MI897>. An industrial high-temperature process for
the preparation of CBrF3 involves the treatment of CHF3 with Br2 in the presence of Cl2<1995SUP1381923>. Bromotrifluoromethane, commercially known as Halon 1301, is beingphased out as a consequence of the Montreal Protocol <1995MI8>.
244 Functions Containing Four Halogens or Three Halogens
(iii) Trifluoroiodomethane
This compound is commercially available. A method for the preparation of CF3I is based on thetreatment of solvated (trifluoromethyl)zinc bromide CF3ZnBr with ICl. The yield is 70% andcomplications with the onus of heavy metal containing wastes, typical of earlier methods, is alsoavoided <1994JFC(67)91>. A patented procedure for the preparation of CF3I calls for theinteraction of pentafluoroethane with I2 in the presence of alkali metal or earth alkali metalsalts <2000FRP2794456>. A flow reactor process carried out at �400 �C in the presence of CuIconverts a 1:1 iodine–trifluoroacetic acid mixture to CF3I <2001MI144>.
6.07.1.2.2 Trichloromethyl halides
(i) Trichlorofluoromethane
This compound is commercially available. The fluorination of tetrachloromethane with HF in thepresence of NH4AlF4 and �-Al2O3 in a high-temperature reactor yields CCl3F as the mainproduct <1990GE(E)P278473>. The cited patent is the latest in a series of closely related patents.Both trichloromethane and tetrachloromethane react slowly with XeF2 to form, inter alia, CCl3F<1993JFC(62)293>.
(ii) Bromotrichloromethane
This compound is commercially available. It can be prepared with 45% yield from CHCl3 andCBr2F2 in the presence of Bu4NHSO4 and KOH <1998PLP173916>. The air labile cubic full-erene solvate C60�12CBrCl3 and the air stable hexagonal solvate C60�12CBrCl3 have been preparedas potential superconductors <2003CM288>.
(iii) Trichloroiodomethane
No further advances have occurred in this area since the publication of chapter 6.07.1.2.2 in<1995COFGT(6)211>.
6.07.1.2.3 Tribromomethyl halides
(i) Tribromofluoromethane
This compound is commercially available. No further advances have occurred in this area sincethe publication of chapter 6.07.1.2.3 in <1995COFGT(6)211>.
(ii) Tribromochloromethane
A 43% yield of the commercially available CBr3Cl is obtained in the reaction of CBr2F2 withCHBr2Cl in the presence of benzyltriethylammonium chloride and KOH <1998PLP173916>.
(iii) Tribromoiodomethane
No further advances have occurred in this area since the publication of chapter 6.07.1.2.3 in<1995COFGT(6)211>.
Functions Containing Four Halogens or Three Halogens 245
6.07.1.2.4 Triiodomethyl halides
(i) Fluorotriiodomethane
No further advances have occurred in this area since the publication of chapter 6.07.1.2.4 in<1995COFGT(6)211>.
(ii) Chlorotriiodomethane
No further advances have occurred in this area since the publication of chapter 6.07.1.2.4 in<1995COFGT(6)211>.
(iii) Bromotriiodomethane
No further advances have occurred in this area since the publication of chapter 6.07.1.2.4 in<1995COFGT(6)211>.
6.07.1.3 Two Similar Halogens
6.07.1.3.1 Difluoromethylene dihalides
(i) Bromochlorodifluoromethane
No further advances have occurred in this area since the publication of chapter 6.07.1.3.1 in<1995COFGT(6)211>. Bromochlorodifluoromethane, formerly commercially available as Halon1211, is being phased out as a consequence of the Montreal Protocol <1995MI8>.
(ii) Chlorodifluoroiodomethane
A 9% yield of CClF2I (b.p. 31–34�C) is obtained (in admixture with other products) in the nickel
catalyzed high-temperature reaction of commercially avavailable 2,2,3-trifluoro-3-(trifluoromethyl)-oxirane (a convenient source of CF2 by thermally induced loss of (CF3)2C(¼O)) with ICl<1996JA8140>.
(iii) Bromodifluoroiodomethane
A 9% yield of CBrF2I is obtained in the nickel catalyzed high-temperature reaction of 2,2,3-trifluoro-3-(trifluoromethyl)oxirane with IBr <1996JA8140>.
6.07.1.3.2 Dichloromethylene dihalides
(i) Dichlorodifluoromethane
Dichlorodifluoromethane (b.p. �28.0 �C, <2001MI897>) is one of the minor products of thenickel catalyzed high-temperature reaction of 2,2,3-trifluoro-3-(trifluoromethyl)oxirane with ICl<1996JA8140>. Both CHCl3 and CCl4 react with XeF2 to form CCl2F2 <1993JFC(62)293>. Thereaction of CCl4 with HF in the presence of an NH4AlF4 catalyst yields CCl2F2 as the minorproduct with CCl3F as the major product <1990GE(E)P278473>. The cited patent is the latest ina series of closely related patents.
246 Functions Containing Four Halogens or Three Halogens
(ii) Bromodichlorofluoromethane
The b.p. of CBrCl2F is 52.5 �C <2001MI897>. No synthetic advances have occurred in this areasince the publication of chapter 6.07.1.3.1 in <1995COFGT(6)211>.
(iii) Dichlorofluoroiodomethane
Dichlorofluoroiodomethane can be obtained by reaction of (dichlorofluoromethyl)tris(dimethyl-amino)phosphonium chloride [(Me2N)3P(CCl2F)]Cl with I2 or ICl <1982JFC(20)89>.
(iv) Bromodichloroiodomethane
No further advances have occurred in this area since the publication of chapter 6.07.1.3.2 in<1995COFGT(6)211>.
6.07.1.3.3 Dibromomethylene dihalides
(i) Dibromodifluoromethane
This compound is commercially available. A 68% yield of CBr2F2 (b.p. 25.0 �C <2001MI897>) isobtained in the nickel catalyzed high-temperature reaction of 2,2,3-trifluoro-3-(trifluoromethyl)oxiranewith Br2 <1996JA8140>. Dibromomethane reacts with XeF2 to form CBr2F2 <1993JFC(62)293>.
(ii) Dibromodichloromethane
This compound is commercially available. A 51% yield of CBr2Cl2 is obtained in the reaction ofCHBrCl2 with CBr2F2 in the presence of Bu4NBr and NaOH <1998PLP173916>.
(iii) Dibromochlorofluoromethane
This compound is commercially available. No further advances have occurred in this area sincethe publication of chapter 6.07.1.3.3 in <1995COFGT(6)211>.
(iv) Dibromofluoroiodomethane
No further advances have occurred in this area since the publication of chapter 6.07.1.3.3 in<1995COFGT(6)211>.
(v) Dibromochloroiodomethane
No further advances have occurred in this area since the publication of chapter 6.07.1.3.3 in<1995COFGT(6)211>.
6.07.1.3.4 Diiodomethylene dihalides
(i) Difluorodiiodomethane
Up to 78% yield of the commercially available CF2I2 is obtained in the nickel catalyzed hightemperature reaction of 2,2,3-trifluoro-3-(trifluoromethyl)oxirane with I2, IBr, or ICl, respectively<1996JA8140>.
Functions Containing Four Halogens or Three Halogens 247
(ii) Dichlorodiiodomethane
No further advances have occurred in this area since the publication of chapter 6.07.1.3.4 in<1995COFGT(6)211>.
(iii) Bromofluorodiiodomethane
No further advances have occurred in this area since the publication of chapter 6.07.1.3.4 in<1995COFGT(6)211>.
(iv) Dibromodiiodomethane
This compound is still unknown.
(v) Chlorofluorodiiodomethane
This compound is still unknown.
(vi) Bromochlorodiiodomethane
This compound is still unknown.
6.07.1.4 Bromochlorofluoroiodomethane
Both the racemic compound and the two enantiomers of bromochlorofluoroiodomethaneCBrClFI have been considered in theoretical work <2000MI3811>, but no syntheses have beenreported so far.
6.07.2 METHANES BEARING THREE HALOGENS
6.07.2.1 Three Halogens and a Chalcogen
6.07.2.1.1 Three halogens and an oxygen function
(i) Trihalomethanols, CHal3OH
(a) Trifluoromethanol. No new preparative procedures for CF3OH have become known. In anion flow tube study, it was shown that CF3OH is formed from (trifluoromethyl)sulfur penta-fluoride CF3SF5 and hydroxide anions <2003MI(223-224)403>. In the environment CF3OHappears to be formed in the upper atmosphere from trifluoromethoxy radicals and ambienthydrogen donors <2001CPL(345)435>.
(b) Trichloromethanol. UV irradiation of methanol�chlorine�nitrogen gas mixtures generates,inter alia, CCl3OH, which again decomposes to C(¼O)Cl2 and HCl <2000CPL(322)97>.
(c) Tribromomethanol. The acidity of the unknown CBr3OH has been investigated by quantumchemical methods <1995JPC12151>. All other CAS references to CBr3OH appear to be in errordue to confusion with 2,2,2-tribromoethanol.
(d) Dichlorofluoromethanol. Transient CCl2FOH is formed by insertion of 1D oxygen atomsinto the C�H bond of CHCl2F <1972JPC1425>.
(e) Chlorodifluoromethanol. Transient CClF2OH is formed by insertion of 1D oxygen atomsinto the C�H bond of CHClF2 <1972JPC1425>.
248 Functions Containing Four Halogens or Three Halogens
(ii) Trihalomethyl ethers, CHal3OR
4-Amino- and 4-nitrophenol can be converted in 52–90% yield into the corresponding trifluoromethylethers CF3OAr by reaction with CCl4 or CCl3F in the presence of HF and one or several of thefollowing catalysts: KF, NaF, SbCl3, SbCl5, SnCl4 TaCl5, TiCl4<2001GEP10030090>. This is by andlarge a rediscovery of earlier findings along the same lines<1982JFC(19)553>. The aliphatic trifluoro-methyl ethers CF3OCH2CF3 and CF3OCH(CF3)2 have been prepared by treatment of the corre-sponding alcohols with CCl4 andHF in the presence of a Lewis acid catalyst. The mixed trihalomethylethers CF2ClOCH(CF3)2 and CCl2FOCH(CF3)2 were also among the products<1995USP5382704>.2-Methoxyaniline has been converted into 2-(trifluoromethoxy)aniline by protection of the aminogroup as an isocyanate (by treatment with C(¼O)Cl2), AIBN catalyzed chlorination of 2-meth-oxyphenyl isocyanate to 2-(trichloromethoxy)phenyl isocyanate (90% yield), halogen exchange withliquid HF at 100 �C, and hydrolysis of 2-(CF3O)C6H4N¼C¼O to 2-(CF3O)C6H4NH2
<1998FRP2763940>. A particularly convenient and general method for the preparation of aliphaticand aromatic trifluoromethyl ethers CF3OR 8 has been found in the shape of the conversion ofalcohols or phenols ROH 1 to the corresponding dithiocarbonates ROC(¼S)SMe 2, which in turnare converted into trifluoromethyl ethers CF3OR 8 by treatment with an N-halo imide such as 1,3-dibromo-5,5-dimethylhydantoin and the commercially available 70% HF/pyridine reagent (Olah’sreagent), cf. Scheme 1. In the case of R=secondary or tertiary alkyl or ArCH2, the milder 50% HF/pyridine reagent is required to prevent the formation of the corresponding fluoride RF. Typicalexamples of 8 thus prepared are 2-benzyloxy-1-bromo-3-(trifluoromethoxy)benzene 1-Br-3-(CF3O)C6H4 (56% yield), methyl 3-(trifluoromethoxy)benzoate 3-(CF3O)C6H4C(¼O)OMe (76%yield), 4-acetoxy-40-(trifluoromethoxy)biphenyl 4-[MeC(¼O)O]C6H4C6H4(OCF3)-4
0 (80% yield),and hexadecyl trifluoromethyl ether CF3O(CH2)15Me (95% yield). The cited papers also reviewearlier methods for the preparation of trifluoromethyl ethers 8 <2000BCJ471, 2001JOC1061,2001MI815>. With 14CS2, correspondingly labeled RO14CF3 can be obtained<2001MI815>. Fluor-ination of a methoxy to a trifluoromethoxy group takes place in the synthesis of the esterCF3CF2CF2OCF(CF3)C(¼O)OCF2CF(OCF3)CClFCClF2 from the acid fluoride CF3CF2CF2O-CF(CF3)C(¼O)F, the ester CF3CF2CF2OCF(CF3)C(¼O)OCH2CH(OMe)CHClCH2Cl, and F2
<2002WOP2002026688>.
Chlorodifluoromethyl ethers (CClF2)OR are converted into trifluoromethyl ethers CF3OR inexcellent yield and purity by treatment with BrF3 <2000JFC(102)363>. Aryl chlorodifluoro-methyl ethers (CClF2)OAr are available both by condensation of the corresponding sodiumphenoxide with CCl2F2 and by halogen exchange between the corresponding trichloromethylether CCl3OAr and liquid HF <2000JFC(103)81, 2001MI191>.
–MeSX
–SX2
8
ROCF3
7
SRO
F F
Me
XSMeRO
F F
6
F–
F–
5
SMeRO
X2S FX+
X+
SMeRO
XS F
4
F–
S
SMeRO
X
3
X+
21
ii. CS2
iii. MeI
i. NaHROH
S
SMeRO
Scheme 1
Functions Containing Four Halogens or Three Halogens 249
The selectivity of the photochlorination of aryl methyl ethers ArOMe with Cl2 to aryl trichloro-methyl ethers CCl3OAr is improved by the removal of traces of the phenol ArOH in the startingmaterial <2000WOP2000012456>. Photochlorination of the chiral methyl 1,2,2,2-tetrafluoroethylethers CF3CHFOMe yields the corresponding chiral trichloromethyl ethers CCl3OCHFCF3
<1995JOC1319>. Reaction of 2,2,3-trifluoro-2-(trifluoromethyl)oxirane with C(¼O)F2 leadsto 2,3,3,3-tetrafluoro-3-(trifluoromethoxy)propanoyl fluoride CF3CF(OCF3)C(¼O)F, which,after hydrolysis and decarboxylation, gives trifluoroethenyl trifluoromethyl ether CF3OCF¼CF2
<1997JOC6160>. Upon treatment with C(¼O)F2 and KF (the synthetic equivalent of potassiumtrifluoromethoxide CF3OK) 2,2,2-trifluoroethyl trifluoromethanesulfonate CF3S(¼O)2OCH2CF3
yields 56% 2,2,2-trifluoroethyl trifluoromethyl ether CF3OCH2CF3 <1995JAP07179385>; cf.<1995JAP07179386>.
Dichlorofluoromethyl ethers (CCl2F)OR have been prepared by treatment of trichloromethylethers CCl3OR with SbF3 and Br2 <1995JOC1319>. Upon treatment with catalytic SbCl5 and anequimolar amount of dichloroacetyl fluoride CHCl2C(¼O)F as the fluoride donor, trichloro-methyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether CCl3OCH(CF3)2 is converted into the corre-sponding dichlorofluoromethyl ether (CCl2F)OCH(CF3)2 <1999JFC(94)1>. A similar procedurewith fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (commercially available as sevo-fluran) as the fluoride donor allows the conversion of trichloromethyl ethers CCl3OR to dichloro-fluoromethyl ethers (CCl2F)OR and to chlorodifluoromethyl ethers (CClF2)OR, ofdichlorofluoromethyl ethers (CCl2F)OR to chlorodifluoromethyl ethers (CClF2)OR, and ofchlorodifluoromethyl ethers (CClF2)OR to trifluoromethyl ethers CF3OR <1998JFC(88)51>.Chlorodifluoromethyl 1,2,2-trichloro-1,2-difluoroethyl ether (CClF2)OCClFCCl2F, among otherproducts, has been obtained by photochlorination of 2-chloro-1,2-difluoroethyl difluoromethylether CHClFCHFO(CHF2) (mixture of diastereomers). Minor products of the same reaction weredifluoromethyl 1,1,2,2-tetrachloro-2-fluoroethyl ether (CHF2)OCCl2CCl2F, dichlorofluoromethyl2,2,2-trichloro-1,1-difluoroethyl ether (CCl2F)OCF2CCl3, and 1,2,2-trichloro-1,2-difluoroethyltrichloromethyl ether CCl3OCClFCCl2F <1997JFC(82)9>.
Aryl bromodifluoromethyl ethers (CBrF2)OAr have been obtained from sodium arenoxidesArONa and CBr2F2 <2001MI191>.
A series of aryl difluoroiodomethyl ethers (CF2I)OAr have been prepared in modest yields bytreatment of CF2I2 with alkyl-, methoxy-, or halo-substituted phenoxides <2000JFC(102)105>.
(iii) Trihalomethyl esters
Trichloromethyl chloroformate CCl3OC(¼O)Cl (the commercially available ‘‘diphosgene’’) has beenmade by exhaustive photochlorination of methyl formate HC(¼ O)OMe or methyl chloroformateClC(¼O)OMe <1998CNP1172102>. A manufacturing concept for bis(trichloromethyl)carbonateCCl3O(C¼O)OCCl3 9 (the commercially available ‘‘triphosgene’’) converts 9 and methanol todimethylcarbonate MeOC(¼O)OMe which is then photochlorinated to 9 of >99% purity. Thisreaction generates 3mol. 9 per mol. 9 originally consumed <2002CNP1336361>. Another patentdescribes the photochlorination of dimethylcarbonate to 9 in 99% yield <1998JAP10007623>.The ester peroxides CF3OC(¼O)OOC(¼O)OCF3 and CF3OC(¼O)OOOC(¼O)OCF3 areformed by photolysis of a mixture of TFAA, CO, and O2. Thermal decomposition ofCF3OC(¼O)OOOC(¼O)OCF3 also furnishes, inter alia, CF3OC(¼O)OOC(¼O)OCF3
<2000IC1195, 2002MI1>.Trifluoromethylnitrite CF3ONO (presumably formed in the reaction of trifluoromethoxy radi-
cals with NO) decomposes at room temperature to C(¼O)F2 and FNO. The somewhat labiletrifluoromethylnitrate CF3ONO2 has been prepared in 15% yield in a pressure reaction betweenCF3OF and NO2. It is also formed by rearrangement of the unstable trifluoromethyl peroxynitriteCF3OONO <2001ZAAC(627)655>.
(iv) Trihalomethyl hypohalites, CHal13OHal2
Three patents disclose new approaches to the synthesis of the commercially available trifluoro-methyl hypofluorite CF3OF. It can be obtained from C(¼O)F2 and F2 in the presence of metalfluorides such as KF and CsF <2003JAP2003081919> and from CO2 and F2 in the presence ofCsF <2002JAP2002003451>.
250 Functions Containing Four Halogens or Three Halogens
Dichlorofluoromethyl hypofluorite (CCl2F)OF and chlorodifluoromethyl hypofluorite(CClF2)OF have been prepared from bis(1-chloro-2,2-difluoroethenyl) ether (CF2¼CCl)2O andOF2. Chlorodifluoromethyl hypofluorite is also formed in the photolysis of a mixture of OF2 and1,3-dichloro-1,1,3,3-tetrafluoropropan-2-one <1968ZOB1410>.
Trifluoromethyl hypochlorite CF3OCl, decomposing rapidly above �78 �C, is formed by inter-action of C(¼O)F2 with ClF in the presence of CsF <1986IS58>.
Trifluoromethyl hypobromite CF3OBr, only observable at low pressure and temperature, hasbeen obtained from CF3OCl and Bu4NBr3 in unspecified yield <1997IC2147>.
Trifluoromethyl hypoiodite CF3OI has been observed as a product of the photochemicaldecomposition of the complex between CF3I and O3 <1985IC4234>.
The hypothetical trichloromethyl hypochlorite CCl3OCl has been the subject of quantumchemical calculations <2000JPC(A)9581>.
The fluorosulfenate CF3OSF has been prepared by UV irradiation of the isomeric sulfinylfluoride CF3S(¼O)F <1988IC2706>.
(v) O-Trihalomethyl peroxides, CHal3OOR
Bis(trifluoromethyl) peroxide CF3OOCF3 is commercially available. Difluorodioxirane CF2O2
reacts with C(¼O)F2 and CsF to form trifluoromethyl fluoroperformate FC(¼O)OOCF3 aswell as oligomers of the type CF3O(OCF2O)nOC(¼O)F. The detailed reaction mechanism hasbeen elucidated by 13C labeling <1999CC1671>. Trifluoromethyl peroxynitrite CF3OONO is apossible transient product of the photoreaction between CF3NO and O2 in an argon matrix<1987JPC3650>. Trifluoromethyl peroxynitrate CF3OONO2 (b.p. 0.9 �C) has been obtained in30–70% yield by photolysis of a mixture of CF3I, NO2, and O2 and removal of by-products bysubsequent treatment with O3 <1998IC6208>; cf. <2001ZAAC(627)655>. Bis(trifluoromethyl)trioxide CF3OOOCF3 (m.p. �138 �C) is most conveniently prepared in up to 87% yield by apressure reaction of CsF, C(¼O)F2, and OF2 cf. <2001ZAAC(627)655>. The possible chemistryof the hypothetical bis(trifluoromethyl) tetroxide CF3OOOOCF3 has been considered theoreti-cally <1997JCS(F)379>. The peroxide CF3OOC(¼O)OCF3 is one of the products of thephotolysis of a mixture of [CF3C(¼O)]2O, CO2, and O2 <2000IC1195>.
(vi) Trihalomethyl sulfonates, CHal3OS(¼O)2R
Trichloromethyl trifluoromethanesulfonate CF3S(¼O)2OCCl3 has been prepared in 90% yieldfrom the mixed anhydride [CF3S(¼O)2O]3B and CFCl3 <1995JFC(73)17>.
(vii) N-Trihalomethoxy compounds, CHal3ON(¼O)nR
No further advances have occurred in this area since the publication of chapter 6.07.2.1.1 in<1995COFGT(6)211>.
(viii) Metal trihalomethoxides, CHal3OM
No further advances have occurred in this area since the publication of chapter 6.07.2.1.1 in<1995COFGT(6)211>.
6.07.2.1.2 Three halogens and a sulfur function
(i) Trihalomethanethiols, CHal3SH
Trifluoromethanethiol CF3SH is formed upon irradiation of trifluoromethanethioic acidCF3C(¼O)SH in an inert gas matrix <1997JST(407)171>.
The reactivity of the hypothetical trichloromethanethiol CCl3SH has been investigated in depthby quantum chemical methods <2002JPC(A)11581>.
Functions Containing Four Halogens or Three Halogens 251
(ii) Trihalomethyl sulfides, CHal3SR
2-Biphenylyl trifluoromethyl sulfide CF3SC6H4Ph-2 has been prepared from the corresponding methylsulfide MeSC6H4Ph-2 by the standard sequence of photochlorination (to give CCl3SC6H4Ph-2)(in 82% yield) and subsequent halogen exchange with HF (86% yield) <1999JAP11049742>.
The syntheses of a large number of geminal bis[(trifluoromethyl)sulfanyl] compounds derivedfrom the ketene 2,2-bis[(trifluoromethyl)sulfanyl]ethenone (CF3S)2C¼C¼O have been described<1998JFC(89)9>.
Sodium hydroxymethanesulfinate (rongalite) HOCH2SO2Na is a useful auxiliary in thepreparation of alkyl trifluoromethyl sulfides CF3SAlk from aliphatic thiols AlkSH and CBrF3
in that it suppresses the competing formation of disulfides AlkSSAlk <2000JFC(105)41>.Trifluoromethyl sulfides CF3SAr and CF3SR have been prepared in a pressure reaction of
CF3CO2K with diaryl disulfides ArSSAr and thiocyanates RSCN, respectively <2001JFC(107)311,2002USP2002042542>. Aryl trifluoromethyl sulfides CF3SAr such as 2-chloro-5-nitrophenyltrifluoromethyl sulfide are available by heating of the corresponding diaryl disulfides ArSSAr withCF3CO2K in boiling tetrahydrothiophene 1,1-dioxide (sulfolane) <1999EP962450>.
A 70% yield of 2-thiazolyl trifluoromethyl sulfide was obtained when 2-(trimethylsilyl)thiazolewas treated with CF3SCl. The alternative reaction between 2-bromothiazole and CF3SCu wasunsatisfactory <2002PS(177)2465>.
Activated aromatic ring positions such as an unsubstituted 4-position of a pyrazole can betrifluoromethylsulfenylated to the corresponding sulfide CF3SAr with S-(trifluoromethyl)trifluoromethanethiosulfonate CF3S(¼O)2SCF3 <2002JAP2002338547>. O-(Trimethylsilyl)-2,2,2-trifluoroethanal hemiaminals CF3CH(OSiMe3)NR2, together with tetrabutylammoniumdifluorotriphenylsilicate (De Shong’s reagent) [Bu4N][Ph3SiF2], convert disulfides RSSR to thecorresponding trifluoromethyl sulfides CF3SR in good yields <2001TL2473>.
A modest yield of benzhydryl and 4,40-disubstituted benzhydryl trifluoromethyl sulfidesCF3SCHAr2 is obtained in the reaction between thiobenzophenone and 4,40-disubstitutedthiobenzophenones, respectively, and commercial trimethyl(trifluoromethyl)silane CF3SiMe3(Ruppert’s compound) in the presence of TBAF <2002HCA1644>. Trimethyl(trifluoromethyl)-silane CF3SiMe3 neatly reacts with thiocyanates RSCN (with TBAF catalysis) <1997TL65> andarenesulfenyl chlorides ArSCl (with TASF, i.e., tris(dimethylamino)sulfonium difluorotrimethyl-silicate, catalysis) <1995JFC(70)255> to form the corresponding trifluoromethyl sulfides CF3SR(30–87% yield) and aryl trifluoromethyl sulfides CF3SAr (59–72% yield), respectively.
The photolysis of mixtures of disulfides RSSR and the corresponding trifluorothioacetateCF3C(¼O)SR (available from TFAA and the corresponding thiol RSH) or trifluoromethanethio-sulfonate CF3S(¼O)2SR (available fromCF3SO2Na, RSSR, and Br2), dissolved inMeCN, constitutesamildmethod for the generation of trifluoromethyl sulfides CF3SR. In this way a highly functionalizedtrifluoromethyl sulfide such as methyl N-(trifluoroacetyl)-S-(trifluoromethyl)-L-cysteinate could beobtained in 60% yield. The reaction fails with aromatic substrates (R=Ar) <1999JOC3813>.
Aromatic diazonium tetrafluoroborates ArN2BF4 react with CF3SCu to give the correspondingaryl trifluoromethyl sulfides CF3SAr in high yields. The reaction fails when the aryl group isdonor substituted <2000CC987>. Activation of CF3SAg, CF3SCu, or (SCF3)2Hg with inorganiciodides was found to promote the formation of aryl trifluoromethyl sulfides CF3SAr in theirreactions with halonitroarenes. Quantitative yields can be achieved <2000JOC1456>. Especiallyactive salts like CF3SM (M=K, Me4N) 10, cf. Scheme 2, can be employed in this reaction<1999JFC(95)171>.
A number of derivatives (such as esters and acid halides) of 2,2-bis[(trifluoromethyl)sulfanyl]-ethanoic acid (CF3S)2CHCO2H, of 2-bromo-2,2-bis[(trifluoromethyl)sulfanyl]ethanoic acid(CF3S)2CBrCO2H, and of 2,2,2-tris[(trifluoromethyl)sulfanyl]ethanoic acid (CF3S)3CCO2H havebeen prepared by standard methods <1996CB1383>.
MeCN10
+ 2MCl
M = K, Me4N
MCF3 SMF
S
ClCl
Scheme 2
252 Functions Containing Four Halogens or Three Halogens
Mixed trihalomethyl sulfides and related compounds such as CF3SSCF3, CF3SSSCF3,CF3SCH2I, CF3SCH2SCF3, (CCl2F)SCF3, (CBrClF)SCF3, and CF3SCH2CN have been obtainedfrom copper(I) trifluoromethanethiolate CF3SCu and various halomethanes. Also, S-(trifluoro-methyl) thiocarbonates and thio-ortho-carbonates are formed <1996JFC(76)7>.
Trifluoromethanide anion, generated by treatment of CHF3 with t-BuOK at �30 �C, can besulfenylated to the corresponding aryl trifluoromethyl sulfides CF3SAr by treatment with ArS-SAr, ArSCl, or PhS(¼O)2SAr in yields ranging from 60% to 90% <1998T13771,2000JOC8848>. Tetracoordinate sulfur intermediates, formed in situ by addition of potassiumt-butoxide to CF3S(¼O)OR or CF3S(¼O)NR2, decompose with formation of CF3
�, which inturn converts aliphatic and aromatic disulfides RSSR to the corresponding sulfides CF3SR inmodest yields <2003SL233>.
1-(1-Pyrrolidino)cyclopentene and 1-(1-pyrrolidino)cyclohexene react with N-[(trifluoromethyl)-sulfanyl]phthalimide to yield the corresponding �-[(trifluoromethyl)sulfanyl]cycloalkanones<2000SC2847> �,�-Bis[(trifluoromethyl)sulfanyl]enamines such as (CF3S)2C¼CHNEt2 areformed in a complicated reaction sequence starting from CF3SCl and certain tertiary ethylaminesEtNR1R2 <1995JFC(70)45>. Trimethylsilyl enol ethers R2C¼C(R)OSiMe3 react with CF3SClto yield the corresponding �-[(trifluoromethyl)sulfanyl]alkanones CF3SCR2C(¼O)R<2002PS(177)1021>.
Aryl dichlorofluoromethyl sulfides (CCl2F)SAr have been prepared in a pressure reaction fromthe corresponding disulfides ArSSAr, sodium hydroxymethanesulfinate HOCH2SO2Na, andCCl3F <2001JOC643>.
(iii) Trihalomethyl sulfoxides and trihalomethyl sulfones, CHal3S(¼O)nR
Different stereoisomers of 3,4-dimethylhexa-1,5-diyne-3,4-diol 11 react with CCl3SCl to give, viathe corresponding bissulfenates 12, the corresponding 1,2-dimethyl-3,4-bis[(trichloromethylsulfi-nyl)methylene]cyclobutenes 13 with full stereochemical control, cf. Scheme 3 <2000TL6923>.9-Fluorenyl trichloromethyl sulfoxide CCl3S(¼O)R (R=9-fluorenyl) has been obtained by base-induced rearrangement of 9-fluorenyl trichloromethanesulfenate CCl3SOR (R=9-fluorenyl).Prop-2-enyl trichloromethyl sulfoxide CCl3S(¼O)CH2CH¼CH2 and 2-methylprop-2-enyltrichloromethyl sulfoxide CCl3S(¼O)CH2C(Me)¼CH2 can be rearranged to (E )-prop-1-enyltrichloromethyl sulfoxide (E)-CCl3S(¼O)CH¼CHMe and 2-methylprop-1-enyl trichloromethylsulfoxide CCl3S(¼O)CH¼CMe2, respectively <1997T13933>. The phosphonate (MeO)2P(¼O)-CH¼C¼CMe2 can be converted into the sulfoxide (MeO)2P(¼O)C(¼C¼CMe2)S(¼O)CCl3 bytreatment with LDA and CCl3S(¼O)Cl <2000PS(166)265>.
While the oxidation of 1,2-bis[(trifluoromethyl)sulfanyl]benzene 1,2-(CF3S)2C6H4 to the corre-sponding bissulfoxide 1,2-[CF3S(¼O)]2C6H4 is readily achieved with MCPBA the correspondingoxidation of the 1,4-isomer apparently requires a different oxidant, i.e., SELECTFLUOR,[1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)], a source ofelectrophilic fluorine <2001USP6215021>.
The insecticidal GABA-gated chloride channel blocker fipronil, 5-amino-1-[2,6-dichloro-4-(tri-fluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile 14 is an importantcommercial trifluoromethyl sulfoxide. Its industrial preparation by oxidation of the correspond-ing sulfide with trifluoroperacetic acid CF3CO3H has been fine tuned <2001WOP0130760>.
1211
C CR CC C
MeO
OMe
C R
S CCl3
SCCl3
–HCl
CCl3SClC CR C
C C
MeOH
HOMe
C R
13
C
C
Me
Me
S
R
S
R
CCl3
CCl3
O
O
Scheme 3
Functions Containing Four Halogens or Three Halogens 253
5-Amino-3-methyl-1-phenylpyrazole can be trifluoromethylsulfinylated in the 4-position by treat-ment with N-[(trifluoromethyl)sulfinyl]succinimide which in turn is obtained from N-lithiosucci-nimide and CF3S(¼O)Cl <2003EUP1331222>.
NN
NC S
NH2
Cl Cl
CF3
CF3
O
14
Protonated trifluoromethanesulfinic acid [CF3SO2H2]+ appears to be the reactive species in the
CF3SO2Na(K)�CF3SO3H mixture which converts arenes ArH with o,p-directing substituents tothe corresponding sulfoxides CF3S(¼O)Ar with predominant p-substitution. Yields rangefrom 55% to 82%. In the absence of activating substituents in the substrate, i.e., with benzene,only 24% yield can be achieved. With CF3OPh as ArH only one product, 1,4-(CF3O)C6H4[S(¼O)CF3] is formed <2001SL550>. 1-Methylpyrrole could be trifluoromethyl-sulfinylated in the 2-position with an in situ reagent [equivalent to [CF3S(¼O)]+] prepared fromCF3SO2Na and Cl3P(¼O) <1999T7243>.
Trimethyl(trifluoromethyl)silane CF3SiMe3, in the presence of catalytic amounts of TBAF,neatly reacts with arenesulfinyl chlorides ArS(¼O)Cl to form the corresponding trifluoromethylsulfoxides CF3S(¼O)Ar (53–61% yield) <1995JFC(70)255>.
Tolyl trifluoromethyl sulfone CF3S(¼O)2C6H4Me-4 has been prepared in 83% yield from4-MeC6H4S(¼O)2F, CF3SiMe3, and TASF <1995JFC(70)255>. Contrary to all other (mostlyaromatic) sulfides tested, oxidation of phenyl trifluoromethyl sulfide CF3SPh with methyl(tri-fluoromethyl)dioxirane Me(CF3)CO2 is >99% selective towards the formation of the correspond-ing sulfoxide CF3S(¼O)Ph and no trace of the sulfone is formed <2002JA9154>.
Bis(trifluoromethyl) sulfoxide CF3S(¼O)CF3 and phenyl trifluoromethyl sulfoxideCF3S(¼O)Ph have been prepared by reaction of dimethyl sulfite (MeO)2S(¼O) and methylbenzenesulfinate PhS(¼O)OMe, respectively, with CsF and CF3SiMe3 <1999JOC2873>.Dichlorofluoromethyl phenyl sulfone (CCl2F)S(¼O)2Ph is the major product (90% yield) ofthe oxidation of the sulfide (CCl2F)SPh with excess H2O2 in AcOH with the correspondingsulfoxide (CCl2F)S(¼O)Ph as the minor product (5% yield) <2001JOC643>.
Methyl methanesulfonate MeS(¼O)2OMe and methyl benzenesulfonate PhS(¼O)2OMe, givemethyl trifluoromethyl sulfone CF3S(¼O)2Me and phenyl trifluoromethyl sulfoneCF3S(¼O)2Ph, respectively, when treated with CsF and CF3SiMe3 <1999JOC2873>. The extre-mely volatile sulfone [CF3S(¼O)2]3CF has been made from the corresponding lithium salt[CF3S(¼O)2]3CLi and F2. Contrary to expectation, it does not constitute a source of F+
<2003JFC(122)233>.
(iv) S-Trihalomethyl thio- and dithioesters, CHal3SC(¼Z)R (Z=O or S)
An S-(trifluoromethyl) androstane-17-carbothioate RC(¼O)SCF3 has been prepared by trifluoro-methylation of the corresponding carbothioic acid RC(¼O)SH with CBrF3 or CClF3
<1998ILP109656>. The S-thioester (CF3S)2CHC(¼O)SCF3 has been obtained by addition ofCF3SH to the ketene (CF3S)2C¼C¼O <1998JFC(89)9>.
(v) Trihalomethanesulfenyl, -sulfinyl, and -sulfonyl halides, CHal13S(¼O)nHal2
The known compounds are listed in Tables 1–3.
254 Functions Containing Four Halogens or Three Halogens
Trifluoromethanesulfinyl chloride CF3S(¼O)Cl can be prepared in situ from the commerciallyavailable trifluoromethanesulfonyl chloride CF3S(¼O)2Cl and trimethyl phosphite (MeO)3P<2001TL1391>. An improved synthesis of trifluoromethanesulfonyl fluoride CF3S(¼O)2F,useful in lithium battery technology, has been achieved by fluorination of MeS(¼O)2F withF2 in perfluoro-2-methylpentane <2003JFC(120)105>. A low yield (18%) synthesis of
Table 1 Trihalomethanesulfenyl halides CHal3SHal
CHal3 CAS RN References
Trihalomethanesulfenyl fluorides CHal3SF
CF3 [17742-04-0] <1993JST(301)65>CClF2 [17742-03-9] <1993JST(301)65>CCl2F [17742-02-8] <1993JST(301)65>CCl3 [2712-94-9] <1981MI399>
Trihalomethanesulfenyl chlorides CHal3SCl
CF3 [421-17-0] commercially availableCClF2 [993-38-4] <1964AG807>CCl2F [2712-93-8] <1993JST(301)65>CCl3 [594-42-3] commercially availableCCl3 (35S labeled) [244082-02-8] <1999MI225>
Trihalomethanesulfenyl bromides CHal3SBr
CF3 [753-92-4] <1964AG807>CClF2 [993-37-3] <1964AG807>CCl2F [993-36-2] <1964AG807>CCl3 [993-35-1] <1964AG807>CBrF2 [993-34-0] <1964AG807>CBr2F [993-32-8] <1964AG807>CBrCl2 [993-33-9] <1964AG807>CBr2Cl [993–31-7] <1964AG807>CBrClF [753-91-3] <1964AG807>CBr3 [993-30-6] <1964AG807>
Trihalomethanesulfenyl iodides CHal3SI
CF3 [102127-62-8] <1992ZAAC(611)114>
Table 2 Trihalomethanesulfinyl halides CHal3S(¼O)Hal
CHal3 CAS RN References
Trihalomethanesulfinyl fluorides CHal3S(¼O)F
CF3 [812-12-4] <1968JA5403>CF3 (13C labeled) [115095-68-6] <1968JA5403>CF3 (18O labeled) [115095-69-7] <1968JA5403>CClF2 [63177-65-1] <1977JFC(9)233>
Trihalomethanesulfinyl chlorides CHal3S(¼O)Cl
CF3 [20621-29-9] <2001USP6316636>CCl2F [156904-01-7] <1992IC492>CCl3 [25004-95-9] commercially available
Trihalomethanesulfinyl bromides CHal3S(¼O)Br
CF3 [20621-30-1] <1988ZAAC(537)169>CCl3 [503844-33-5] <1968ACS3256>
Trihalomethanesulfinyl iodides CHal3S(¼O)I
CF3 [108863-76-9] <1988ZAAC(537)169>
Functions Containing Four Halogens or Three Halogens 255
(CClF2)S(¼O)2Cl has been achieved by reaction of zinc hydroxymethanesulfinate (HOCH2
SO2)2Zn with CBrClF2 and subsequent chlorination of the intermediate (CClF2)SO2H salt withCl2 <1989JOC2452>.
(vi) Trihalomethanesulfenic, -sulfinic, and -sulfonic derivatives, CHal3S(¼O)nZR
Benzyl trifluoromethansulfenate CF3SOCH2Ph has been prepared in a one-pot reaction byoxidation of benzyl trifluoromethyl sulfide CF3SCH2Ph with H2O2 <2001USP6316636>. Tri-fluoromethanesulfinates CF3S(¼O)OR and trifluoromethanesulfinamides CF3S(¼O)NR1R2 areavailable by reaction of the corresponding precursors ROH and R1R2NH, respectively, with anin situ reagent (equivalent to [CF3S(¼O)]+) prepared from CF3SO2Na and Cl3P(¼O)<1999T7243>. 9-Fluorenyl trichloromethanesulfenate CCl3SOR (R=9-fluorenyl) has been pre-pared in 86% yield by the standard method <1997T13933>. Potassium trifluoromethanesulfinateCF3SO2K, an important synthetic intermediate, is available from a pressure reaction betweenCF3CO2K and SO2 <2002USP2002042542>.
Propargylic alcohols HC�CCR1R2OH react with trifluoromethanesulfinyl chloride CF3S(¼O)Clto give the corresponding sulfinates CF3S(¼O)OCR1R2C�CH which in turn can be further con-verted by rearrangement into the corresponding allenyl sulfones CF3S(¼O)2CH¼C¼CR1R2
<2001TL1391>.In situ generation of trifluoromethanesulfinyl chloride CF3S(¼O)Cl from CF3S(¼O)2Cl and
(MeO)3P allows the convenient conversion of the appropriate amines RNH2 to the trifluoro-methanesulfinamides CF3S(¼O)NHR <1998SUL63>. Sodium trifluoromethanesulfinateCF3SO3Na, useful as intermediate in the synthesis of CF3S(¼O)Cl, has been obtained by thetreatment of 2-chlorocyclohexyl trifluoromethyl sulfone with NaOH <2001USP6316636>.
Trifluoromethanesulfinamides CF3S(¼O)NHR are also formed by the interaction ofN-sulfinylamines R-N¼S¼O with CF3SiMe3 and Me4NF (75–85% yield) <2002TL3029>.
Treatment of trifluoromethoxy substituted aliphatic ethers with a mixture of commerciallyavailable trifluoromethanesulfonic anhydride Tf2O and CF3SO3H leads to trifluoromethoxysubstituted trifluoromethanesulfonic esters such as CF3S(¼O)2O(CH2)2OCF3 useful as alkylatingagents <2001JOC1061>.
Trifluoromethanethiosulfonic acid S-esters CF3S(¼O)2SR, including CF3S(¼O)2SCCl3, havebeen prepared from CF3SO2Na and the appropriate sulfenyl chlorides RSCl (or bromides RSBr).Trifluoromethaneselenosulfonic acid Se-esters CF3S(¼O)2SeR are accessible with the corre-sponding selenyl chlorides RSeCl (or bromides RSeBr) as starting materials. Yields range from50% to 95% <1996JOC7545>.
Table 3 Trihalomethanesulfonyl halides CHal3S(¼O)2Hal
CHal3 CAS RN References
Trihalomethanesulfonyl fluorides CHal3S(¼O)2F
CF3 [335-05-7] <1994IC3281>CClF2 [64544-26-9] <1979S972>CBrF2 [73043-96-6] <1979S972>CF2I [73043-97-7] <1979S972>CCl3 [1495-34-7] <1970MI795>
Trihalomethanesulfonyl chlorides CHal3S(¼O)2Cl
CF3 [421-83-0] commercially availableCClF2 [1495-29-0] <1993IC5007>CCl2F [1495-33-6] <1993IC5007>CCl3 [2547-61-7] commercially availableCCl3 (35S labeled) [244082-03-9] <1999MI225>CBrF2 [146691-88-5] <1992MI274>
Trihalomethanesulfonyl bromides CHal3S(¼O)2Br
CF3 [15458-53-4] <2001WOP0127076>CBrF2 [146691-81-8] <1992MI274>CCl3 [993-51-1] <1997JCR(S)6>
256 Functions Containing Four Halogens or Three Halogens
N-[(Trifluoromethyl)sulfinyl]trifluoromethanesulfonamide CF3S(¼O)2NHS(¼O)CF3 has beenprepared in a lengthy procedure starting from bis(trifluoromethyl) disulfide CF3SSCF3,N,N-dichlorotrifluoromethanesulfonamide CF3S(¼O)2NCl2, and trifluoromethanesulfinylchloride CF3S(¼O)Cl <2002JFC(115)129>. The chemistry and the materials science aspectsof the commercially available trifluoromethanesulfonimide [CF3S(¼O)2]2NH have beenreviewed <2002JCS(P1)1887>. S,S-Dimethyl-N-[(trifluoromethyl)sulfonyl]iminodithiocarbonateCF3S(¼O)2N¼C(SMe)2, a useful intermediate for the preparation of N-[(trifluoromethyl)sul-fonyl]ureas and -guanidines, has been obtained in 85% yield by treatment of S,S-dimethyliminodithiocarbonate HN¼C(SMe)2 with Tf2O <2003JFC(124)151>.
N-Sulfinyltrichloromethanesulfonamide CCl3SO2N¼S¼O has been prepared by treatmentof the corresponding sulfonamide with SOCl2 <1982LA545>. The compoundCCl3S(¼O)N[S(¼O)2Me]2 has been prepared by trichloromethanesulfinylation of silver(I)trifluoromethanesulfonimidate [MeS(O)2]2NAg with CCl3S(¼O)Cl <1998ZN(B)734>.
(vii) Metal trihalomethanethiolates, CHal3SM
Particularly nucleophilic salts of trifluoromethanethiol 10 can be obtained by reaction in MeCNof thiophosgene C(¼S)Cl2 with anhydrous KF or Me4NF, cf. Scheme 2 <1999JFC(95)171>. Thepreparation of the trifluoromethanethiolates of copper(I), CF3SCu (commercially available),silver(I), CF3SAg, and mercury(II), (CF3S)2Hg (commercially available) and their use forthe introduction of CF3S groups into organic compounds have been reviewed<1996JFC(76)7>. The important synthetic intermediate CF3SCu has been prepared in 98%yield from CS2, AgF, and CuBr <2001USP6215021>. Bis(trifluoromethyl) disulfide CF3SSCF3
reacts with tetrakis(dimethylamino)ethene (Me2N)2C¼C(NMe2)2 to form the salt (Me2N)2C+–
C+(NMe2)2�2CF3S� the anion of which can be alkylated or arylated to give trifluoromethyl
sulfides such as CF3SCH2Ph, CF3SC5NF4, and CF3SC6H3(NO2)2-2,4 in 80–95% isolated yield<2000JCS(P1)2183>.
6.07.2.1.3 Three halogens and an Se or Te function
(i) (Trihalomethyl) selenium compounds, CHal3SeR
Tetramethylammonium trifluoromethaneselenolate [Me4N][CF3Se], a useful synthetic intermedi-ate, is available in 65% yield from red selenium, CF3SiMe3, and Me4NF <2003JFC(123)183>.
The syntheses of a large number of geminal bis[(trifluoromethyl)selanyl] compounds derivedfrom the ketene 2,2-bis[(trifluoromethyl)selanyl]ethenone (CF3Se)2C¼C¼O have been described<1998JFC(89)9>. O-(Trimethylsilyl)-2,2,2-trifluoroethanal hemiaminals CF3CH(OSiMe3)NR2,
together with tetrabutylammonium difluorotriphenylsilicate [Bu4N][Ph3SiF2], convert aromaticdiselenides ArSeSeAr to the corresponding trifluoromethyl selenides CF3SeR in good yields<2001TL2473>. Trifluoromethanide anions, generated from CHF3 in different ways, react withdiphenyl diselenide PhSeSePh to give phenyl trifluoromethyl selenide CF3SePh in fair yield<2000JOC8848>.
Trimethyl(trifluoromethyl)silane CF3SiMe3, in the presence of catalytic amounts of TBAF,neatly trifluoromethylates selenocyanates RSeCN to the corresponding trifluoromethyl selenidesCF3SeR (58–75% yield) <1997TL65>. A large number of new trifluoromethylselanyl compoundssuch as (CF3Se)3CF, (CF3Se)3CCl, (CF3Se)3CBr, (CF3Se)3CC(SeCF3)3, and (CF3Se)2C¼C(SeCF3)2have been obtained from tris[(trifluoromethyl)selanyl]methylium hexafluoroarsenate [(CF3Se)3C][AsF6]as the common precursor <1996CB1383>.
N-[(Trifluoromethyl)selanyl]succinimide has been prepared from trifluoromethaneselenyl chlor-ide CF3SeCl and silver(I) succinimidate <1996CB1383>.
A particularly mild method for the preparation of phenyl trifluoromethyl selenide CF3SePh in58% yield consists of the photolysis of Se-phenyl trifluoromethanselenosulfonateCF3S(¼O)2SePh (prepared from CF3SO2Na, PhSeSePh, and Br2) in the presence of equimolarPhSeSePh <1999JOC3813>. Bis(trifluoromethyl) selenoxide CF3Se(¼O)CF3 has been preparedin 84% yield from dimethyl selenite (MeO)2Se(¼O), CsF, and CF3SiMe3 <1999JOC2873>. Thesame selenoxide CF3Se(¼O)CF3 has also been prepared from bis(trifluoromethyl) selenideCF3SeCF3 and hypofluorous acid HOF <2000JFC(102)301>.
Functions Containing Four Halogens or Three Halogens 257
(ii) (Trihalomethyl)tellurium compounds, CHal3TeR
The chemistry of (trifluoromethyl)tellurium compounds has been reviewed. The key compoundsdescribed as useful intermediates are CF3TeCF3, CF3TeTeCF3, CF3TeI, and (CF3Te)2Hg<2001PS(171-172)113>. Aromatic Te-(trifluoromethyl) tellurocarboxylates ArC(¼O)TeCF3
are available by reaction of the corresponding acyl chlorides ArC(¼O)Cl with trifluoromethyltrimethylstannyl telluride CF3TeSnMe3. This same tellurium reagent replaces two of the threechlorine atoms of 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride) with (trifluoromethyl)telluranylgroups.
The reaction between CBr4 and CF3TeSnMe3 is assumed to give tetrakis(trifluoromethyl)tellur-ium (CF3)4Te which decomposes spontaneously to bis(trifluoromethyl) ditelluride CF3TeTeCF3
and tetrakis[(trifluoromethyl)telluranyl]ethene (CF3Te)2C¼C(TeCF3)2 <1999JFC(94)195>.Bis(trifluoromethyl)tellurium dichloride (CF3)2TeCl2 reacts with AgNSO to yield the labile tell-urium compound (CF3)2Te(NSO)2 <2000JFC(102)301>.
6.07.2.2 Three Halogens and a Group 15 Element
6.07.2.2.1 Three halogens and a nitrogen function
(i) Trihalomethylamines, CHal3NR2
(a) Primary trihalomethylamines. No further advances have occurred in this area since thepublication of chapter 6.07.2.2.1 in <1995COFGT(6)211>.
(b) Secondary trihalomethylamines. The serendipitous formation of a secondary trifluoro-methylamine was observed when the attempted simple halogen exchange of 2-(trichloromethyl)-phenyl isocyanate 15 with HF yielded 2-[(trifluoromethyl)amino]benzoyl fluoride 16 rather thanthe expected 2-(trifluoromethyl)phenyl isocyanate 17 <1982JFC(19)553>.
N
CCl3
C
O
NH
C
CF3
F
O
1516
HF
HF
17
N
CF3
C
O
(c) Tertiary trihalomethylamines. Electrochemical fluorination of methyl 2-methyl-3-(dimethyl-amino)propanoate leads to 2% of the perfluorinated product (CF3)2NCF2CF(CF3)C(¼O)OCF3,together with, inter alia, 36% (CF3)2NCF2CF(CF3)C(¼O)F and 5% (CF3)2NC3F7. Similarresults were seen in the electrofluorination of methyl 3-(dimethylamino)butanoate<1994JFC(66)193>. Solution-phase fluorination with F2 of TMEDA in the presence of NaFgives a 20% yield of the perfluorinated product (CF3)2NCF2CF2N(CF3)2 <2003JFC(123)233>.Secondary amines R1R2NH can be converted into the corresponding tertiary trifluoromethy-lamines CF3NR1R2 by treatment with BuLi, CS2, and MeI, and subsequent fluorination of theresulting methyl dithiocarbamate with [Bu4N][H2F3] and 1,3-dibromo-5,5-dimethylhydantoin.Labeled compounds 14CF3NR1R2 are obtained with 14CS2 <2001MI815>. A large number oftertiary trifluoromethylamines such as perfluoro-1,4-dimethylpiperazine CF3N(CF2CF2)2NCF3
258 Functions Containing Four Halogens or Three Halogens
have been obtained by electrofluorination of 1-[2-(methoxycarbonyl)ethyl]-4-methylpiperazineMeN(CH2CH2)2NCH2CH2C(¼O)OMe and related compounds <2001JFC(108)21>. Hexakis-(trifluoromethyl)tetrazane (CF3)2NN(CF3)N(CF3)N(CF3)2 is formed in 90% yield upon photolysis ofN-chloro-N,N0,N0-tris(trifluoromethyl)hydrazine (CF3)2NN(Cl)CF3 <1995AG(E)586>.
(ii) N-(Trihalomethyl)amides, CHal3NRC(¼O)R
The imines CF3N¼CF(CF3) and CF3N¼CF(C2F5) react with AcOH with loss of acetylfluoride to yield the N-(trifluoromethyl)amides (CF3)NHC(¼O)CF3 and (CF3)NHC(¼O)C2F5,respectively <1988IZV833>.
(iii) Trihalomethyl isocyanates, CHal3N¼C¼O; trihalomethyl isocyanide dihalides,CHal3N¼CHal2 and N-(trihalomethyl)carbodiimides, CHal3N¼C¼NR
All known trihalomethyl isocyanates CHal3N¼C¼O (Hal¼F, Cl, Br) have been shown to existin equilibrium with their halotropic isomers, the halocarbonyl isocyanide dihalidesCHal2¼NC(¼O)Hal with the latter strongly predominating <1996ZOB1715>.
(a) Trifluoromethyl isocyanate. No further advances have occurred in this area since thepublication of chapter 6.07.2.2.1 in <1995COFGT(6)211>.
(b) Trichloromethyl isocyanate. This compound is listed in the 2003–2004 Aldrich catalog.However, early as well as more recent work has shown that its equilibrium with chlorocarbonylisocyanide dichloride Cl2C¼NC(¼O)Cl lies completely to the right <1996ZOB1715>.
(c) Tribromomethyl isocyanate. No further advances have occurred in this area since thepublication of chapter 6.07.2.2.1 in <1995COFGT(6)211>.
(d) Triiodomethyl isocyanate. There is no record of this compound.(e) Fluorodichloromethyl isocyanate. The isomeric fluorocarbonyl isocyanide dichloride
Cl2C¼NC(¼O)F is available from Cl2C¼NC(¼O)Cl and AgF <1968AG(E)630>.(f) Bromodifluoromethyl isocyanate. Photochemical insertion of CO into the N�Br bond of
CF2¼NBr gives a 55% yield of (CBrF2)N¼C¼O. No halotropic equilibrium withCF2¼NC(¼O)Br or other isomers has been reported <1988JOC4443>.
(g) Trifluoromethyl isocyanide difluoride. Pyrolysis of alkali metal 2-[bis(trifluoromethyl)-amino]-2,2-difluoroethanoates such as (CF3)2NCF2CO2Na gives, among other products,difluoro-N-(trifluoromethyl)methanimine CF3N¼CF2 <1999JFC(95)161>. The defluorinationof CF3N¼CF2 with Ph3P proceeds smoothly to yield 80%–90% trifluoromethyl isocyanideCF3NC <1995IC3114>.
(iv) N-Halo(trihalomethyl)amines, CHal13NRHal2
N,N-Dichlorotrifluoromethylamine CF3NCl2 is available by addition of ClF to ClCN in thepresence of catalytic CsF <1991IC2699>. Addition of ClF to the hydrazone (CF3)2NN¼CF2
produces N-chloro-N,N0,N0-tris(trifluoromethyl)hydrazine (CF3)2NN(Cl)CF3 <1995AG(E)586>.
(v) N-(Trihalomethyl)hydroxylamines, CHal3NR1OR2; trihalonitrosomethanes CHal3NO,trihalonitromethanes, CHal3NO2, and related compounds
N,N-Bis(trifluoromethyl)-O-fluorohydroxylamine (CF3)2NOF is available from difluoro-N-(trifluoromethyl)methanimine CF3N¼CF2 and OF2 in the presence of CsF, but decomposesspontaneously to trifluoronitrosomethane CF3NO and CF4. If the same reagents are used in theratio 2:1 the hydroxylamine derivative 1,1,3,3-tetrakis(trifluoromethyl)-2,1,3-oxadiazane(CF3)2NON(CF3)2 is formed in 77% yield <1999JFC(99)145>. In the presence of CsF trimethyl(tri-fluoromethyl)silane CF3SiMe3 reacts with NOCl to form trifluoronitrosomethane CF3NO in92% yield and with excellent purity <2002CC1818>. Another possibility for the preparation ofCF3NO is the reaction of (CF3)2Cd with NOCl (yield 98%) <1995JFC(73)273>.
Trichloronitrosomethane CCl3NO can be prepared on a commercial scale by photonitrozationof CHCl3 with NOCl <2001JAP2001002625>.
Functions Containing Four Halogens or Three Halogens 259
Tribromonitrosomethane CBr3NO and the mixed trihalonitrosomethanes CClF2NO,CCl2FNO, CBrCl2NO, and CBr2ClNO are on record in the older literature (with the extremelyhazardous mercury(II) fulminate as the most common ultimate synthetic precursor)<1980SA(A)75> as is CBrF2NO <1953JCS2075>.
A substantially simplified synthesis of trifluoronitromethane CF3NO2 has been achieved in theshape of the photoreaction of CF3I with NO2 (35% yield; only highly volatile by-products areformed which can be readily removed by treatment with excess CsF). This method could also beused to prepare the labeled CF15
3 NO2 <2002JFC(117)181>. A yield of 47% CF3NO2 is achievedin the reaction of isopropyl nitrate Me2CHONO2 with (trifluoromethyl)zinc bromide CF3ZnBrand AlCl3 <1995JFC(73)273>.
Trichloronitromethane (chloropicrin) CCl3NO2 is commercially available as a versatile C1 reagent.Tribromonitromethane (bromopicrin), along with bromonitromethane and dibromonitromethane,
has been obtained by bromination of nitromethane with t-butyl hypobromite Me3COBr in thepresence of hex-1-ene (yield 71%) <1976JOC1285>. Treatment of nitromethane with a Br2/Cl2mixture in the presence of water and NaOH yields 33% CBrCl2NO2, 35% CBr2ClNO2, 13%CCl3NO2, and 18% CBr3NO2 <1964USP3159686>.
Neither triiodonitrosomethane CI3NO nor triiodonitromethane CI3NO2 are known except for atheoretical treatment of CI3NO2 <1972JST321>.
Chlorodifluoronitromethane CClF2NO2 has been prepared by oxidation of chlorodifluoroni-trosomethane CClF2NO <1953JCS2075>. The compounds CClF2NO2 and CBrF2NO2, respec-tively, have been obtained by treatment of difluoronitroethanoic acid with XeF2 and Cl2 or Br2.Corresponding treatment of chlorofluoronitroethanoic acid with XeF2, Cl2 and Br2, respectively,gives CCl2FNO2 and CBrClFNO2 <1988IZV2639>. The compounds CCl2INO2 and CF2INO2
have been considered theoretically <1972JST321>.
(vi) N-(Trihalomethyl)sulfenamides, CHal3SNR1R2
Simple trifluoromethanesulfenamides CF3SNR1R2 have been prepared from CF3SCl and second-ary aliphatic amines <1995JFC(70)45>. Several imide type heterocycles have been N-sulfenylatedwith CCl3SCl <2000PS(161)213>.
(vii) Metal (trihalomethyl)amides, CHal3NRM
No further advances have occurred in this area since the publication of chapter 6.07.2.2.1 in<1995COFGT(6)211>.
(viii) Miscellaneous compounds
Trifluoromethyl azoxy compounds have been reviewed. In the case of (Z)-1-fluoro-2-(trifluoro-methyl)diazene 2-oxide (Z)-CF3N(¼O)¼NF, obtained from the reaction of trifluoronitro-somethane CF3NO with tetrafluorohydrazine N2F4, the structure could be confirmed bygas-phase electron diffraction although quantum chemical calculations showed the corresponding1-oxide to be more stable by 12 kcalmol�1. Apparently, the energy of activation for thecorresponding isomerization is of considerable magnitude <2002IC6125>.
6.07.2.2.2 Three halogens and a phosphorus function
When triphenyl phosphite (PhO)3P is treated with excess CBrF3 and (Et2N)3P, an 85% yield oftris(trifluoromethyl)phosphine (CF3)3P is obtained <1996JFC(79)103>. Dichlorophosphines RPCl2react with equivalent amounts of CBrF3 and tris(diethylamino)phosphine (Et2N)3P to give thecorresponding bis(trifluoromethyl)phosphines (CF3)2PR 18, which upon further elaboration yieldbis(trifluoromethyl)-substituted phosphoranes. The phosphines 18 can be methylated with methyltrifluoromethanesulfonate CF3S(¼O)2OMe to give the corresponding phosphonium sulfonates[(CF3)2P(R)Me][CF3SO3] <2002HAC650>. When bis(trifluoromethyl)phosphine (CF3)2PH istreated with tetraethylammonium cyanide Et4NCN, the bis(trifluoromethyl)phosphanide anion
260 Functions Containing Four Halogens or Three Halogens
[(CF3)2P]� 19 is formed (with evolution of HCN). The phosphanide anion 19 is only stable
below �30 �C, but can be considerably stabilized as a CS2 adduct, [(CF3)2PCS2]� <2002IC2260>.
Alkylation of 19 with ethylene ditosylate 4-MeC6H4S(¼O)2OCH2CH2OS(¼O)2C6H4Me-4leads to the bisphosphine (CF3)2PCH2CH2P(CF3)2 <2001IC3113>. Solution-phaseperfluorination of 1,2-bis(dimethylphosphino)ethane Me2PCH2CH2PMe2 affords thebisphosphorane (CF3)2P(F2)CF2CF2P(F2)(CF3)2 <2000JFC(102)333>. A poor yield (15%) of1,2-bis[bis(trifluoromethyl)phosphino)]ethane (CF3)2PCH2CH2P(CF3)2 has been obtained upontreatment of 1,2-bis(dichlorophosphino)ethane Cl2PCH2CH2PCl2 with CBrF3 and (Et2N)3P<1992TL7601>. Both the tetraphosphetane [(CF3)P]4 and the pentaphospholane [(CF3)P]5decompose to bis(trifluoromethyl)diphosphene (CF3)P¼P(CF3) which can be trapped incycloadditions with alka-1,3-dienes <1995ZN(B)189>.
The bis(trichloromethyl)phosphine 2,4,6-Me3C6H4P(CCl3)2 can be prepared in good yield byreaction of the phosphorane 2,4,6-Me3C6H4P¼CCl2 with CCl4 and (Et2N)3P <1992ZOB948>.
6.07.2.2.3 Three halogens and an As, Sb, or Bi function
Trihalomethylarsines such as (CF3)3As, (CF3)2As(CClF2), and CF3As(CF2Cl)2 can be obtainedfrom solvent-free (CF3)2Cd and AsCl3. Also the corresponding dihaloarsoranes R1R2R3AsHal1Hal2
are formed <1995JOM(503)C51>.Trifluoronitrosomethane CF3NO reacts with trifluoromethylarsine (CF3)AsH2 to form the
hydroxylamine derivative (CF3)As[ONH(CF3)]2 and with bis(trifluoromethyl)arsine (CF3)2AsHto give the analogous (CF3)2AsONH(CF3). The latter reacts with bis(trifluoromethyl)nitroxylradicals (CF3)2NO to give, inter alia, (CF3)2AsON(CF3)2 <1996JFC(79)111>.
The metal complex (CF3)2AsMn(CO)5 can be made from tetrakis(trifluoromethyl)diarsane(CF3)2AsAs(CF3)2 and pentacarbonylmanganese(I) iodide Mn(CO)5I <2002ZAAC(628)2523>.
The cycloarsanes [(CF3)As]4.5 decompose to bis(trifluoromethyl)diarsene (CF3)As¼As(CF3)which can be trapped in cycloadditions with alka-1,3-dienes <1995ZN(B)189>.
Tris(trifluoromethyl)antimony (CF3)3Sb has been prepared in 61% yield from (CF3)PbPh3 andSbI3 <2000OM2603>.
Ligand exchange of the bismuthane compounds ArBiBr2 and Ar2BiCl with (CF3)2Cd yields(CF3)2BiAr and (CF3)BiAr2, respectively. The former rapidly disproportionates to (CF3)BiAr2and (CF3)3Bi <1994JFC(69)219>. Tris(trifluoromethyl)bismutane (CF3)3Bi and copper(II) acetatereact with each other to form (CF3)2BiOAc and CF3Bi(OAc)2. This mixture can be used intrifluoromethylations, for instance of [Bu4N][SPh], where CF3SPh is formed in undeterminedyield <2000JFC(106)217>.
6.07.2.3 Three Halogens and a Metalloid
6.07.2.3.1 Three halogens and a silicon function
Trimethyl(trifluoromethyl)silane (CF3)SiMe3, trimethyl(trichloromethyl)silane (CCl3)SiMe3, andtrichloro(trichloromethyl)silane (CCl3)SiCl3 are commercially available. The silanes (CClF2)SiMe3and (CBrF2)SiMe3 are available by interaction of CBrClF2 and CBr2F2, respectively, withaluminum and Me3SiCl <1997JA1572>.
Catalytic thermal decarboxylation of silyl trichloroacetates CCl3C(¼O)OSiMe2R gives thecorresponding trichloromethylsilanes (CCl3)SiMe2R <1995IZV150>. Insertion of diaminosily-lenes (R1R2N)2Si into a C�Cl bond of CCl4 gives the corresponding amino-substituted1-chloro-2-(trichloromethyl)disilanes (R1R2N)2Si(CCl3)Si(Cl)(NR1R2)2 <2002JA4186>.
A minuscule yield (3%) of 2,2-dibromo-1,1,3,3,5-pentamethyl-5-(tribromomethyl)-1,3,5-(trisila-cyclohexane) 21 has been obtained by photobromination of 1,1,3,3,5,5-hexamethyl-1,3,5-trisila-cyclohexane 20 <2000CJC1388>.
Me2Si
SiMe2
SiMe2 Br2
hν
2021
Me2Si
Si
SiMe2
Br Br
Me CBr3
Functions Containing Four Halogens or Three Halogens 261
6.07.2.3.2 Three halogens and a boron function
Potassium tetrakis(trifluoromethyl)borate K[B(CF3)4] is available via treatment of ammoniumtetracyanoborate NH4[B(CN)4], dissolved in liquid HF, with ClF3 or ClF. The primary step inthis conversion is assumed to be an addition to the C�N triple bond, cf. Scheme 4<2001CEJ4696>. As a rule of thumb trifluoromethyl derivatives of tricoordinate boron areunstable while those of tetracoordinate boron are much more accessible. Thus, whiletris(trifluoromethyl)borane (CF3)3B still eludes its isolation and characterization, its impressivelystable adduct with carbon monoxide (CF3)3BCO (m.p.�9 �C) has been prepared by partialhydrolysis of the salt K[B(CF3)4]. When (CF3)3BCO is dissolved in CD3CN at room temperatureCO is evolved and the acetonitrile adduct (CF3)3B�NCCD3 is formed <2002JA15385>.(Dimethylamino)bis(trifluoromethyl)borane (CF3)2BNMe2 22 reacts with N-sulfinylcarboxamidesRC(¼O)N¼S¼O by [2+4]-cycloaddition leading to 23 and with N-sulfinylcarbamatesROC(¼O)N¼S¼O by concomitant [2+4]- and [2+2]-cycloaddition leading to 24 and 25,respectively, cf. Scheme 5 <2002ZAAC(628)2299>.
6.07.2.3.3 Three halogens and a germanium function
Iodotris(trifluoromethyl)germane (CF3)3GeI is commercially available.The compound (CF3)GePh3 has been prepared from Ph3GeCl and (CF3)2Cd�glyme
<2000OM2603>. When CF3I is heated with GeBr4 and copper bronze at 180 �C, tribromo(tri-fluoromethyl)germane (CF3)GeBr3 is formed <2001MI765>.
The phosphaethene HP¼C(F)NEt2 has been converted into (CF3)3GeP¼C(F)NEt2 by treat-ment with (CF3)3GeI and Et3N <2000ZAAC(626)1141>. Displacement reactions of (CF3)3GeIand (CF3)2GeI2 with Hg(NSO)2 lead to (CF3)3GeNSO 26 and (CF3)2Ge(NSO)2 27, respectively.Compound 26 suffers loss of SO2 with formation of sulfur diimide (CF3)3GeN¼S¼NGe(CF3)328. The corresponding condensation of 27 leads to the medium sized heterocycle(CF3)2Ge(N¼S¼N)2Ge(CF3)2 29, cf. Scheme 6 <1999JFC(96)147>.
NH4[B(CN)4]ClF
HF K[B(CF3)4]
R C N ClF
R CF2
NCl2 HFR CF3 + HNCl2
Scheme 4
(CF3)2BNMe2
22
RC(=O)N=S=O
ROC(=O)N=S=O
N
OB(CF3)2
NMe2S
R
O
23
S
N B(CF3)2
NMe2
O
ROC(=O)
24
N
OB(CF3)2
NMe2S
RO
O
25
+
Scheme 5
262 Functions Containing Four Halogens or Three Halogens
6.07.2.4 Three Halogens and a Metal Function
6.07.2.4.1 Trihalomethyl alkali and earth alkali metals, CHal3M (M=Li, Na, K, Cs, Mg)
A transient species, tentatively identified as (triiodomethyl)magnesium chloride (CI3)MgCl,has been observed in the reaction system triiodomethane–isopropylmagnesium chloride<2001OM5310>.
6.07.2.4.2 (Trihalomethyl)aluminum, -gallium, -indium, and -thallium compounds, CHal3MRn
(M=Al, Ga, In, Tl)
Tris(trifluoromethyl)indium(III) (CF3)3In is available by cocondensation of trifluoromethyl radi-cals with indium vapor <1986MI701>.
Phenylbis(trifluoromethyl)thallium(III) (CF3)2TlPh and bis(trifluoromethyl)thallium(III) acetate(CF3)2Tl(OAc) have been prepared from (CF3)2Cd�glyme and PhTl(OAc)2 and Tl(OAc)3,respectively <1989IC2816>.
6.07.2.4.3 (Trihalomethyl)tin and -lead compounds, CHal3MRn (M=Sn(II), Sn(IV), Pb(IV))
The reaction of trimethyltin chloride Me3SnCl with solvent-free (CF3)2Cd gives a 90% yieldof (CF2Cl)SnMe3 and (CF3)SnMe3 in a 2:1 ratio <1995JOM(503)C51>. The compounds(CF3)SnPh3, (CF3)2SnPh2, (CF3)PbPh3, (CF3)2PbPh2, and (CF3)3PbPh are available by treatmentof the corresponding halo(phenyl)metal compounds with (CF3)2Cd�glyme <2000OM2603>.
6.07.2.4.4 (Trihalomethyl)zinc, -cadmium, and -mercury compounds, CHal3MR (M=Zn, Cd,Hg(II))
The chemistry of (trifluoromethyl)zinc bromide (CF3)ZnBr, especially with regard to the prepara-tion and utilization of complexes, has been reviewed <1996JPR(338)283>.
Donor-free bis(trifluoromethyl)cadmium (CF3)2Cd is formed in quantitative yield from Et2Cdand CF3I <1995JOM(503)C51>.
The mercury(I) compound CF3HgHgCF3 has not been observed yet in keeping with itstheoretically predicted instability. Apparently other factors counteract the expectedly stabilizingeffect of the strongly electronegative CF3 groups on the strength of the Hg�Hg bond<1995JST(358)195>.
(CF3)3GeI (CF3)3GeN=S=O
26
26
(CF3)3GeN=S=O–SO2
–SO2
(CF3)3GeN=S=NGe(CF3)3
28
(CF3)2GeI2Hg(NSO)2
Hg(NSO)2
CF3
Ge NN
CF3
S O
SO
27
27
CF3
Ge NN
CF3
S O
SO
N S NGeGe
N S N CF3
CF3CF3
CF3
29
Scheme 6
Functions Containing Four Halogens or Three Halogens 263
6.07.2.4.5 (Trihalomethyl)copper, -silver, and -gold compounds, CHal3MRn (M=Cu(I),Cu(III), Ag(I), Ag(III), Au(I), Au(III))
Tris(trifluoromethyl)silver(III) (CF3)3Ag has been used as a starting material for heterolepticargentates(III) containing trifluoromethyl groups. The anions tetrakis(trifluoromethyl)cuprate(III)[Cu(CF3)4]
�, tetrakis(trifluoromethyl)argentate(III) [Ag(CF3)4]�, and tetrakis(trifluoromethyl)-
aurate(III) [Au(CF3)4]�, available by oxidation of lower-valency (trifluoromethyl)metal compounds,
have been employed in the construction of superconducting BEDT-TTF salts <1999CCR(190-192)781>. (Trifluoromethyl)gold(I) phosphine complexes (CF3)AuPR3 have been prepared fromCF3SiMe3 and the corresponding alkoxides Au[OCH(CF3)2]PR3. The analogous reaction withCCl3SiMe3 leads to the corresponding labile products (CCl3)AuPR3. Starting from the gold(III)compound (CF3)Me2Au(OPh), CF3SiMe3, and a ligand PR3 the gold(III) complexes(CF3)Me2AuPR3 are obtained <2000ICA(309)151>.
6.07.2.4.6 Miscellaneous trihalomethyl transition metal compounds, CHal3MRn (M=transition metal)
Attempts at oxidative addition of CCl4, CBr4, and CI4 to the Rh(I) complex RhCl(CO)(PPh3)(H-NEt2) failed to yield the corresponding trichloromethyl-, tribromomethyl-, and triiodomethyl-substituted Rh(III) complexes, halogenation being observed instead <1998OM4966>.
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Functions Containing Four Halogens or Three Halogens 267
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268 Functions Containing Four Halogens or Three Halogens
Biographical sketch
Alexander Senning Born 1936 in Riga, Latvia,Alexander Senning studied chemistry inMunich, Germany (1954–1959) and Uppsala,Sweden (1960–1962). He obtained a Ph.D. inorganic chemistry from Uppsala University1962, joined the Department of Chemistry,Aarhus University, Denmark as assistant pro-fessor (1962–1965) and served as associateprofessor during 1965–1993. During a sabba-tical leave (1973–1975), he was head of theresearch laboratory of the drug companyA/S Alfred Benzon, Copenhagen, Denmark.He joined the Danish Engineering Academy(DIA), Lyngby, Denmark, later part of TheTechnical University of Denmark (DTU),Lyngby, Denmark, as professor of organicchemistry in 1993, until his retirement in2003. Research interests: organic sulfur chem-istry, medicinal chemistry. Extensive activitiesas book and journal editor. A detailed chemi-cal autobiography is available in Sulfur Rep.,2003, 24, 191–253.
Jørgen Øgaard Madsen Born 1940 in Aars,Denmark, Jørgen Øgaard Madsen studiedchemistry in Aarhus, Denmark (1962–1971)and received an M.Sc. (1967) and a Ph.D.(1972) in organic chemistry from AarhusUniversity, Denmark. He held an assistantprofessorship at the Department of Chemis-try, Aarhus University, Denmark (1967–1971)and joined the Department of Organic Chem-istry (later Department of Chemistry) of theTechnical University of Denmark (DTU) asassociate professor (1972 to present).Research interests: heterocyclic enamines,stereospecific syntheses with baker’s yeast,natural product chemistry, analytical organicchemistry (HPLC, MS).
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 243–269
Functions Containing Four Halogens or Three Halogens 269
6.08
Functions Containing Two
Halogens and Two Other
Heteroatom Substituents
G. VARVOUNIS and N. KAROUSIS
University of Ioannina, Ioannina, Greece
6.08.1 INTRODUCTION 2726.08.2 TWO HALOGENS AND TWO CHALCOGEN FUNCTIONS 2726.08.2.1 Two Halogens and Two Oxygen Functions 2726.08.2.1.1 Difluoro compounds 2726.08.2.1.2 Dichloro and dibromo compounds 274
6.08.2.2 Two Halogens and Two Sulfur Functions 2746.08.2.2.1 Difluoro compounds 2746.08.2.2.2 Dichloro, dibromo, and diiodo compounds 277
6.08.2.3 Two Halogens, an Oxygen, and a Sulfur Function 2786.08.2.4 Two Halogens and Other Chalcogen Functions 278
6.08.3 TWO HALOGENS AND ONE CHALCOGEN FUNCTION 2796.08.3.1 Two Halogens, a Chalcogen, and a Nitrogen Function 2796.08.3.1.1 Oxygen compounds 2796.08.3.1.2 Sulfur compounds 280
6.08.3.2 Two Halogens, a Chalcogen, and Other Functions 2806.08.4 TWO HALOGENS AND TWO GROUP V ELEMENT FUNCTIONS 2816.08.4.1 Two Halogens and Two Nitrogen Functions 2816.08.4.1.1 Diamines and their derivatives 2816.08.4.1.2 Cyclic compounds 281
6.08.4.2 Two Halogens and Two Phosphorus Functions 2826.08.4.2.1 Bis(phosphonates) 2826.08.4.2.2 Cyclic compounds 2846.08.4.2.3 Miscellaneous compounds 285
6.08.4.3 Two Halogens, a Nitrogen, and a Phosphorus Function 2876.08.5 TWO HALOGENS AND ONE GROUP V ELEMENT FUNCTION 2886.08.5.1 Two Halogens, a Phosphorus, and a Metalloid or Metal Function 2886.08.5.2 Two Halogens, a Nitrogen, and a Metalloid Function 289
6.08.6 TWO HALOGENS AND TWO METALLOID FUNCTIONS 2906.08.6.1 Two Halogens and Two Silicon Functions 2906.08.6.1.1 Linear carbosilanes 2906.08.6.1.2 Cyclic carbosilanes 291
6.08.7 TWO HALOGENS AND TWO METAL FUNCTIONS 292
271
6.08.1 INTRODUCTION
Compounds or functionalities that consist of a central carbon atom attached to two halogens andtwo other heteroatoms that include chalcogens (O, S, Se, or Te), group V elements (N, P, As, Sb,Bi, B, Si, or Ge), main group metals (Sn, Pb, Al, Ga, In, Tl, Be, Mg, Ca, Sr, Ba, Li, Na, K, Rb, orCs), and transition metals (Cu, Ag, Au, Zn, Cd, Hg, Ti, Zr, Hf, Cr, Mo, W, Mn, Fe, Co, Ni, Pd,or Pt) are generally rare. The most frequently encountered halogen is by far fluorine, withchlorine in the second place. One example of a mixed halogen is known whereas mixed hetero-atoms are quite common. The most common heteroatom combinations are two oxygen, twophosphorus, and two sulfur atoms.
6.08.2 TWO HALOGENS AND TWO CHALCOGEN FUNCTIONS
6.08.2.1 Two Halogens and Two Oxygen Functions
6.08.2.1.1 Difluoro compounds
Fluorocarbonylhypofluorite, FC(O)OF, is a relatively unstable product prepared in low yieldfrom the UV irradiation of a mixture of F2 and bis(fluoroformyl)peroxide. The reactions ofFC(O)OF have been limited to the preparation of difluorodioxirane, bis(fluoroxy)difluoro-methane, and chloroxyfluoroxydifluoromethane <1995COFGT(6)249>. The yield of FC(O)OFwas greatly improved by using a 12W low-pressure UV lamp in place of a 350W medium-pressure Hg lamp, as reported in the literature. Furthermore in the reaction of FC(O)OF withClF, the yield of chloroxyfluoroxydifluoromethane was improved by using CsF doped with H2Oinstead of dry CsF <1995IC6221>. The chemistry of this compound has not yet been investi-gated. Difluorodioxirane is one of the most stable dioxiranes known. It was originally preparedby passing a 1:1 (v/v) mixture of FC(O)OF and ClF over a CsF catalyst <1995COFGT(6)249>.An improvement over this method has been achieved by using Cl2 and the new catalyst KHF2;difluorodioxirane was obtained in moderate but higher yields <1999CC1671>. The O�O bondlength in difluorodioxirane is 157.6 pm, and is the longest O�O bond ever calculated andmeasured. This theoretically explains why it is a powerful oxidant and can readily undergoreactions that are typical of dioxiranes. It transfers oxygen to alkenes, forming epoxides andCOF2 in high yield. Its reaction with 13COF2 in the presence of CsF was used to show that itreacts by ring opening of the O�O bond (Equation (1)). A reasonable mechanistic proposal(Scheme 1) predicts trifluoromethoxy anion attack on the dioxirane peroxide bond to giveCF3OOCF2O
�, which loses fluoride to form 1 or reacts further with dioxirane to form newoligomeric peroxides 2–4. The 13C distribution makes it clear that the predominant reaction isattack of CF3O
� on the dioxirane at oxygen and not at the more electropositive carbon.
CsF + 13COF3 13CF3OOC(O)F + 13CF3O(OCF2O)nOC(O)F
–50 °C, 16 h
70% 13C 7% 13C67% 13C10% 13C67% 13C
1 2–4 (n = 1–3)
OO
F
F
ð1Þ
Bis(fluoroxy)difluoromethane reacts with tetrafluoroethylene and trans-1,2-dichloroethylene togive bisethers of formula (RO)2CF2. Bis(fluoroxy)difluoromethane also reacts thermally andphotochemically with perfluoro Dewar benzene; the reaction products were mainly complexcopolymer mixtures, whereas a structure containing 1,1-difluoro-1,3-dioxolane was isolated in6% yield <1995COFGT(6)249>. Previous preparations of halogenated 2,2-difluoro-1,3-dioxo-lanes used multistep processes but often in low or inconsistent yields <1976USP3978030>.Later the addition of bis(fluoroxy)difluoromethane to halogenated alkenes (CX2¼CX2) gavea better yield of 2,2-difluoro-1,3-dioxolanes <1995COFGT(6)249>. This method was furtherimproved by carrying out the reaction of bis(fluoroxy)difluoromethane with halogenatedalkenes (CF2¼CFCF3, CF2¼CFOCF2CF3, CF2¼CHCF3, CF3CF¼CFCl, CFBr¼CFBr,
272 Functions Containing Two Halogens and Two Other Heteroatom Substituents
CCl2¼CCl2, CHCl¼CHCl, CH2¼CHCl, CF2¼CFCl, (CF3)2CFCF¼CFCF3, CF2¼CFBr,and CF2¼CF2) in the presence of halogenated inert solvents (CF2Cl2, CFCl3, and perfluoropo-lyethers) as well as in neat olefin. The halogenated 2,2-difluoro-1,3-dioxolanes were obtained in43–95% yields, together with 1,2-difluorotetrahalogenoethanes as side products. Continuous,semicontinuous or batch procedures were used depending on the physicochemical properties ofthe olefin <1995JFC(71)111>.
4-(2,2-Difluoro-1,3-benzodioxol-4-yl)-1H-pyrrole-3-carbonitrile 5 is a fungicide which ismetabolized by poultry into the N-hydroxy derivative. The latter has been synthesized inseven steps and 23% overall yield from 2,2-difluoro-1,3-benzodioxole-4-carboxylic acid 6<1989EUP333685>. The 2,2-difluoro-1,3-benzodioxole ring remains intact throughout the synth-esis <1995JOC4302>. 6,6-Difluoro-1,3-dioxolo[4,5-f]benzimidazole-2-thione 7 was converted intothe 2-chlorodioxolobenzimidazole 8 by chlorine (Scheme 2) <2001GEP10005277>. Apparently8 was also prepared by heating dioxobenzimidazol-2-one 9 with phosphoryl chloride under HCl.Compound 9 is an intermediate for the preparation of compounds with fungicidal activity<2001GEP10005277>.
N
O
O
NC
F
F
H
O
O F
F
CO2H
5 6
2,2-Difluorobenzo[1,3]dioxole-4-carbaldehyde 13 (Scheme 3) was prepared in three stepsfrom 4-methylbenzo[1,3]dioxole 10. The latter and 2,20-azobisisobutyronitrile (AIBN) were heatedwith chlorine at 70 �C and then at 150 �C to induce chlorination to both C-2 and the methylgroup. 4-Dichloromethyl-2,2-dichlorobenzo[1,3]dioxole 11 thus obtained was fluorinated by HFat �15 �C to give 2,2-difluoro derivative 12, in high yield. Conversion of the CHCl2 group in 12into an aldehyde group in 13 required heating in formic acid <1997EUP759433>.
O
OF
F N
NS
H
H
O
OF
F N
NCl
HO
OF
F N
NO
H
H
Cl2, MeOH, 0 °C96%
POCl3, HCl, ∆
7 9
85%
8
Scheme 2
OO
F
F
13CF3OOC(O)F
O
OFF
13COF2 F– 13CF3O–
13CF3O– 13CF3OOCF2O– – F
–
– F
–13CF3(OCF2O)nOCF2O– 13CF3(OCF2O)nOC(O)F
2–4 (n = 1–3)
1
n
+
Scheme 1
Functions Containing Two Halogens and Two Other Heteroatom Substituents 273
A process for producing fluorinated alkyl ethers 15 from fluorinated alcohols 14, by the actionof HF in the presence of BF3, is claimed in a patent (Equation (2)) <1995USP5382704>.
C
H
OHRR
HF, BF3, CCl4
RC
OC
OC
R
F
F
H RR H
R = CF2CF3, (CF2)2CF3, or (CF2)3CF3
14 15ð2Þ
6.08.2.1.2 Dichloro and dibromo compounds
The synthesis and reactions of these compounds remains an area very little investigated. Interestwas focused in developing more efficient methods to synthesize dichlorodiphenoxymethane 17and dichloroformals 19 <1995COFGT(6)249>. It has been claimed in a patent that the yield of17 may be increased over the previous methods, by heating 16 in a mixture of PCl3 and POCl3 at160–175 �C, while passing chlorine into the reaction mixture (Equation (3)) <1998JAP10182538>.Another patent claims that TiCl4 as catalyst in the reaction between thionocarbonates 18 andSO2Cl2 increases the efficiency in the synthesis of dichloroformal derivatives 19, where R is CCl3,CF3, C(NO2)3, C(NO2)2Me, CF(NO2)2, CF2CF3, CF2NO2, or CCl(NO2)2 (Equation (4))<1997USP5631406>.
OPh
Ph Cl2, 160–175 °C Cl
Cl
PhO
PhO+ PCl3 + POCl3 91%
16 17
ð3Þ
Cl
Cl
RCH2O
RCH2OS
RCH2O
RCH2O TiCl4
1918
+ SO2Cl2 ð4Þ
6.08.2.2 Two Halogens and Two Sulfur Functions
6.08.2.2.1 Difluoro compounds
Bis(trifluorothio)difluoromethane was first observed as a by-product in electrochemical fluorina-tion (ECF) of carbon disulfide. Later it was shown that this compound could be prepared in highpurity by direct fluorination of CS2. Oxidative additions to the SF3 groups and controlled BF3-catalyzed solvolysis in liquid SO2 to give difluoromethanedisulfinyldifluoride 20 have beendescribed. The chemistry of the latter with nitrogen nucleophiles has been investigated in detail
O
O
O
O Cl
Cl
CHCl2Me
AIBN, Cl2
O
O F
F
CHCl2
O
O F
F
CHO
10 11
13
70 °C then 150 °C
Anhyd. HF, –15 °C
12
HCO2H
100 °C
Scheme 3
274 Functions Containing Two Halogens and Two Other Heteroatom Substituents
<1995COFGT(6)249>. This work has been extended to the preparation of difluoromethane-bis(sulfinic acid) 21 by allowing moist air to come into contact with 20 for 3 weeks (Equation (5)).In this reaction no detectable amounts of the anhydride 23, expected as an intermediate, werefound. Single crystals of the anhydride 23 were isolated after salt 22 was hydrolyzed slowly by tracesof moisture while stored at 8 �C (Equation (6)) <1998JFC(89)55>.
F S
F S
FF
O
O
F S
F S
OHOH
O
O
Moist air
–78 °C, 3 weeks
20 21
ð5Þ
Cs [F2C(SF3)2F]F
F
S
SO
O
O
Traces of moisture
8 °C, 2–3 weeks22
23
–+ð6Þ
While ECF in anhydrous HF was used to prepare bis(fluorosulfonyl)difluoromethane fromCH2(SO2F)2 <1997JFC(83)145>, the preparation of F2C(SO2Ph)2 required first the reaction ofPhSO2CHF2 and NaOH in a two-phase system to give PhSO2CF2SPh, and second oxidation ofthe latter with H2O2 <1995COFGT(6)249>. Recently, F2C(SO2Ph)2 was prepared fromPhSCHF2 by reaction with PhSO2Cl in the presence of aqueous NaOH, followed by oxidationof the product PhSO2CF2SPh with H2O2 <2002IC6118>. Bis(trifluoromethylsulfonyl)methane 24was first prepared by reacting methylmagnesium halides with trifluoromethanesulfonylfluoride inEt2O <1956JCS173>. Later the synthesis was improved by simply replacing Et2O by THF. ECFof 24 in anhydrous HF gave difluoromethyl derivative 25 in 25% yield, together with 5% ofCF3SO2F (Equation (7)) <1998JFC(91)9>. Compound 25 was first obtained in traces by thetreatment of 26 with elemental fluorine <1994JFC(67)27>.
H2C(SO2CF3)2 F2C(SO2CF3)2 + CF3SO2FAnhyd. HF, e–
ECF
24 25 (25%) 5%
ð7Þ
S
S
SO
O
O
O
OO
26
The condensation of BrCF2Cl with sodium thiophenoxides 27 gave bis(thiophenol)difluoro-methanes 28 in good yields. The authors postulated an ionic mechanism for the reaction(Equations (8) and (9)) <1981TL1997>.
4-XC6H4SNa + BrCF2ClDMF, –40 °C F
F
SC6H4X-4
SC6H4X-4
27 28
X = Cl or NO2ð8Þ
4-XC6H4SCF2 + 4-XC6H4SBr 28X = Cl or NO2
–ð9Þ
The related reaction of sodium thiophenoxide with BrCF2Cl in dimethyl formamide (DMF) at�40 �C gave four products, the bromo and hydrogenated derivatives 29 and 30 and the chloroand bis(thiophenol)difluoromethane derivatives 31 and 32, in 60% overall yield (Equation (10)).Repetition of this reaction in the presence of nitrobenzene, a known inhibitor of electron-transferprocesses, greatly reduced the yield of 32 (Equation (11)). This result indicates that 32 is formedthrough a radical chain mechanism. The condensation between dichlorodifluoromethane CF2Cl2
Functions Containing Two Halogens and Two Other Heteroatom Substituents 275
and sodium thiophenoxide under UV irradiation produced three products, 30 and 31 as minorproducts with 32 as the major product (Equation (12)). These facts strongly indicate thatthe reactions leading to 32 occur through a radical mechanism as depicted in Scheme 4<1983JOC1979>.
F
F
SPh
SPh
DMFPhSNa + BrCF2Cl PhSCF2Br + PhSCF2H + PhSCF2Cl +
–40 °C29 (9%) 30 (3%) 31 (5%) 32 (43%)
ð10Þ
DMFPhSNa + BrCF2C + PhNO2 29 + 30 + 31 + 32
–40 °C52% 2% 2% 5%
ð11Þ
PhSNa + CF2Cl2DMF, –40 °C
hν30 + 31 + 32
6% 6% 22%
ð12Þ
The reaction of CF2Cl2 with PhSK 33a and 4-MeC6H4SK 33b in DMF under 2 atm pressuregave sulfides 34 as major products while 35 and difluoromethylbis(arylsulphides) 36 as minorproducts (Equation (13)) <1984CC793>.
DMF, 2 atm F
F
SAr
SArArSK + CF2Cl2
a, Ar = Phb, Ar = 4-MeC6H4
ArSCF2Cl + ArSCF2H +
34a (62%)34b (44%)
35a (8%)35b (8%)
36a (7%)36b (6%)
33 ð13Þ
The work on the reactivity of dichlorodihalomethanes with thionate anions has been extendedto CF2I2. Sodium 4-chlorothiophenoxide 37 and CF2I2 react in a 2:1 ratio in diglyme at roomtemperature to afford bis(4-chlorothiophenol)difluoromethane 38 in 43% yield (Equation (14)).Repeating the reaction by changing the molar ratio of 37 to CF2I2 into 1:2 resulted in a drasticdrop of the yield of 38 to 9% and the formation of two major products disulfide 39 anddifluoromethane 40 (Equation (15)). Even better, 38 was formed in 60% yield by the action of37 on 4-ClC6H4SCF2I in DMF <2000JFC(102)105>.
F
F
SC6H4Cl-4
SC6H4Cl-4
Diglyme
ratio 2:137
38
4-ClC6H4SNa + CF2I2
43%ð14Þ
37 + CF2I2Diglyme
ratio 1:239 (28%) 40 (35%) 9%
4-ClC6H4SSC6H4Cl-4 + 4-ClC6H4SCF2I + 38 ð15Þ
Halogen exchange reactions occur when bis(pentafluorothiophenol)dichloromethane 41 isheated with SbF3, SbF5, or CsF. Reaction of 41 with an excess of SbF3 at 150 �C gave dithio-carbonate 43 as the main product and small amounts of bis(pentafluorothiophenol)difluoro-methane 44 and disulfide 42 (Equation (16)). The reaction of 41 with SbF5 at 90 �C resulted inan increase in the formation of difluoromethyl derivative 44 but the main product was thedisulfide 42. (C6F5S)2CClF, C6F5SCF3, and dithiocarbonate 43 were also identified among the
PhSCF2Cl PhSCF2 Cl–
PhSCF2 PhS– PhSCF2SPh
PhSCF2SPh BrCF2Cl PhSCF2SPh BrCF2Cl
32
+
+
+ +
–
–
–
–
Scheme 4
276 Functions Containing Two Halogens and Two Other Heteroatom Substituents
reaction products. At 225 �C the reaction of 41 with excess anhydrous CsF without solvent gavedifluoromethane 44 and polysulfides 46 as major products together with disulfide 42 and chloro-fluoromethane 45 as minor products (Equation (17)). All these compounds were difficult toobtain pure so were identified by 19F-NMR and GC-MS data <1999JFC(98)17>.
SbF3 F
F
SC6F5
SC6H5150 °C(C6F5S)2 + (C6F5S)2CO +
41 42 (6%) 43 (75%) 44 (16%)
(C6F5S)2CCl2 ð16Þ
CsF F
Cl
SC6F5
SC6H5
F
X
SC6F5
S(C6F4S)nC6H5225 °C
41
45
42 + 44 + +
46 X = Cl or F n = 1, 2, or 3
ð17Þ
6.08.2.2.2 Dichloro, dibromo, and diiodo compounds
In this category of compounds, the major interest has been the synthesis and reactions of haloge-nated 1,1,3,3-tetraoxo-1,3-dithietanes, halogenated 1,1,3,3,5,5-hexaoxo-1,3,5-trithianes, halogenated[1,3]dithioles, [1,3]dithiole-1,1-dioxides, and [1,3]dithiole-1,1,3,3-tetraoxides, dichloromethanedisul-fenyl chloride, and bis(alkyl or arylsulfonyl)dihalogenomethanes <1995COFGT(6)249>.
An interesting rearrangement of chloromethylsulfenylchloride 47 into 1-adamantylsulfonyldichloromethyl pentachlorophenyl disulfide 48 occurred when 47 was left in CHCl3 for a fewdays (Equation (18)). In addition, refluxing an ethereal solution of 47 led to a quantitative yield ofthiosulfonate 49 (Equation (19)). These reactions are postulated to occur via concerted mechan-isms supported by AM1 calculations and from an experimental point of view, as the reactionstake place in solvents of low polarity <1994JCS(P1)1251>.
SC
S Cl
ClS
O
O R1
R2
SC
S S
Cl
ClO
O R1
R2
CHCl3, 5 d
R1 = 1-adamantyl, R2
= C6Cl547 48
ð18Þ
SC
S R2
ClS
O
O R1
Cl
ClC
S SR1
Cl
SR2
OOEt2O, ∆, 40 min
R1 = 1-adamantyl, R2
= C6Cl5
47 49
ð19Þ
Bis(substitutedsulfonyl)dihalogenomethanes for all four halogens have been known for overhundred years. Methods of synthesis include direct chlorination or bromination of gem-disul-fones, halogenation of potassium salts of monohalogenated gem-disulfones, and the halogenationof benzeneiodonium ylides with halosuccinimides <1995COFGT(6)249>. An improved synthesisof bis(trifluoromethylsulfonyl)methane 50 was accomplished by the action of methylmagnesiumchloride on trifluoromethanesulfonylfluoride. The reaction of N-chlorosuccinimide (NCS),N-bromosuccinimide (NBS), and N-iodosuccinimide (NIS) in carbon tetrachloride with 50 leadsto the formation of the corresponding dihalogenomethanes 51 (Equation (20)) <1998JFC(91)9>.
CCl4 X
X
SO2CF3
SO2CF3
H
H
SO2CF3
SO2CF3 X = Cl, Br or I
50 51a, X = Cl 76%51b, X = Br 78%51c, X = I 39%
N
O
O
X+ 2
ð20Þ
Functions Containing Two Halogens and Two Other Heteroatom Substituents 277
A study of the interaction of pentafluorothiophenol 52 and CCl4 in the presence of AlCl3 led tothe conclusion that at room temperature, 60 �C, or 80 �C and irrespective of the amount of CCl4and AlCl3 used, dichloromethane 53 was formed as the main product together with minorproducts chloromethane 54 and disulfide 55 (Equation (21)). The origin of observed products isdepicted in Scheme 5. The stability of compound 53 toward hydrolysis or further reaction withstarting material and compound 54 is attributed to the inefficient stabilization of the adjacentcarbocationic center that is involved in these reactions <1999JFC(98)17>.
AlCl3, CCl4 Cl
Cl
SC6F5
SC6F552
+ (C6H5S)3CCl + (C6F5S)2
5354 55
C6F5SHð21Þ
6.08.2.3 Two Halogens, an Oxygen, and a Sulfur Function
Earlier work on this category of compounds is represented only by MeOCCl2SCl synthesized by theaddition of chlorine to either MeOC(S)SMe or MeOC(S)SSC(S)OMe or MeOC(S)SSC(S)OMe<1995COFGT(6)249>.
Treatment of phenols or alcohols ROH with NaH, CS2, and then with MeI led to high yields ofdithiocarbonates 55. Oxidative desulfurization–fluorination of dithiocarbonates 55 was carriedout using tetrabutylammonium dihydrogentrifluoride (TBAH2F3) with NBS in CH2Cl2 to afforddifluoro(methylthio)methylethers 56 (Scheme 6). Methyl ethers 56 were converted readily intotrifluoromethyl ethers ROCF3 by reaction with 70% HF in pyridine and 1,3-dibromo-5,5-dimethylhydantoin <2000BCJ471>.
6.08.2.4 Two Halogens and Other Chalcogen Functions
Tetrahalogeno 1,3-diselenetanes, 1,3-ditelluretanes, and 1,3-selenatelluretanes are known, mostcommon being the tetrafluoro derivatives. Iodo derivatives are unknown <1995COFGT(6)249>.Several difluoro(phenylseleno)methylethers 60 have recently been reported. Difluoromethylben-zene selenide 57 was prepared by the treatment of diphenyl diselenide with NaBH4 in a 2:1 ratio of
AlCl3
Cl–
AlCl3
Cl–
52
C6F5SH + [CCl3...Cl...AlCl3]
53 54
δ+ δ–
C6F5SCCl2...Cl...AlCl3δ+ δ–
52 δ+ δ– 52
C6F5SCCl3
(C6F5S)2CCl2 (C6F5S)2CCl...Cl...AlCl3 (C6F5S)3CCl
Scheme 5
RO SMe
STBAH2F3
NBS, CH2Cl2R O SMe
FF
55 56
R Yield (%)
4-n-C6H13C6H4 364-MeOC6H4 334-PhCH2OC6H4 434-PrnOC(O)C6H4 423-MeOC(O)C6H4 324-BrC6H4 43
R Yield (%)
4-MeC6H4 644-PrnC6H4 584-BrC6H4CH2CH2 19PhCH2CH2CH2 15n-C16H33 94-PhC6H4 234-(4-BrC6H4)C6H4 28
Scheme 6
278 Functions Containing Two Halogens and Two Other Heteroatom Substituents
EtOH/DMF and then with CF2Br2. Oxidation of 57 led to the formation of oxide 58 (Scheme 7).Compound 58 was reacted with acetic anhydride in the presence of cyclic ethers 59 in refluxingCH2Cl2 to give difluoro(phenylseleno)methyl compounds 60 (Equation (22)). The reaction ofselenoxide 58 with Ac2O and (4-MeOC6H4Se)2 in THF provided AcOCH2CH2CH2CH2OCF2SePhand AcOCH2CH2CH2CH2OCF2SeC6H4Me-4 <1995JOC370>.
Z
H
Rn58 +
Ac2O, CH2Cl2 F
F
Z(CH2)nCH(R)OAc
SePh
59 60
R Z n Yield (%)
Me O 1 34H O 2 60H O 3 87Me O 3 56H O 4 74H S 3 53
ð22Þ
6.08.3 TWO HALOGENS AND ONE CHALCOGEN FUNCTION
6.08.3.1 Two Halogens, a Chalcogen, and a Nitrogen Function
6.08.3.1.1 Oxygen compounds
Several compounds of the general formula X2C¼N-R (where X is F or Cl and R=F, Cl, CF3,or CF2CFClY where Y is F, Cl, or Br) proved to be good electrophiles. They reacted withsubstrates such as FSO2OX, F5SOCl, and F3CO2H to give the corresponding addition productsFSO2OCF2NFX, F5SOCCl2NCl2, F3COOCF2NHCF3, and F3COOCF2NHCF2CF2CFClX(where X=F, Cl, or Br). The synthesis and reactions of 3,3-difluoro-3-(trifluoromethyl orpentafluorothio)oxaziridines have also been described <1995COFGT(6)249>.
The difluorocarbimide double bond in 61 is saturated in 20 min at room temperature by SF6OClto give difluoromethane derivative 62 (Scheme 8). The reaction of difluorocarbimide 64 with(CF3)3COCl is much slower and requires 1 day to give difluoromethane derivative 65 (Scheme 9).Irradiation of 62 and 65 gives rise to tetrazanes 63 and 66, respectively <1995IC5049>.
(PhSe)2
i. NaBH4, EtOH, DMFF2HCSePh
H2O2, CH2Cl2SePhF2HC
O
57 58ii. CF2Br
Scheme 7
CF3(C3F7)NN=CF2 + SF5OCl
F
F
OSF5
NN
CF3F3C
ClF
F
OSF5
NN
CN
NCF3
C3H7
FFOSF5
C3H7
F3C
20 min
61
62 63
hν
Scheme 8
(CF3)2NN=CF2 + (CF3)3COCl
F
F
OC(CF3)3
NN
CF3F3C
ClF
F
OC(CF3)3
NN
CN
NCF3
CF3
F FOC(CF3)3
F3CF3C
1 day
64
65 66
hν
Scheme 9
Functions Containing Two Halogens and Two Other Heteroatom Substituents 279
6.08.3.1.2 Sulfur compounds
Representatives of this category of compounds are F5SCF2NF2, FSCF2NF2, Et3N+CF2SO2
�,R+CF2SCF2SO2
� (where R is quinucidine), and FCl(SCl)NCS <1995COFGT(6)249>.Isocyanatodifluoromethanesulfonyl fluoride 69 was prepared in good yield from azidocarbonyldi-
fluoromethanesulfonyl fluoride 68, which was obtained by the reaction of sodium azide with chlor-oformyldifluoromethanesulfonylfluoride 67 (Scheme 10). Compound 69 is extremely sensitive tomoisture. Autocatalytic fragmentation is observed with water (Scheme 11) <1997JFC(84)135>.
6.08.3.2 Two Halogens, a Chalcogen, and Other Functions
Generally, work on this category of compounds is very limited. Most of it is focused ondifluoromethanes (such as F3CPHCF2OMe and C2F5PHCF2OMe) derived respectively fromF3CP¼CF2 and C2F5P¼CF2 by the addition of methanol. Sulfinic salt (EtO)2P(O)CF2SO2Nawas formed from (EtO)2P(O)CF2Br and sodium sulfite or sodium dithionite, andPhSO2CX2HgPh was synthesized by the addition of the anion of halogenated sulfonesPhSO2CHX2 to PhHgCl (where X is Cl or Br) <1995COFGT(6)249>. Recently, the reaction ofpolyfluorinated ether 70 with hexaethylphosphorus triamide (HEPT) and chlorotrimethylsilane inbenzonitrile as solvent was described to give the stable silane 71, in a reaction where the silyl etherwas used as a transfer reagent (Equation (23)) <1995IC13>.
F
F
OC6F5
SiMe3
PhCNC6F5OCF2Br + HEPT + Me3SiCl
7071
ð23Þ
Phenyl(trimethylsilyl)difluoromethyl sulfide 73 can be prepared in 85% yield by the reaction ofbromodifluoromethylphenyl sulfide 72 with magnesium metal and Et3SiCl in DMF at 0 �C. Sulfide 73was oxidized with 3-chloroperoxybenzoic acid (m-CPBA) in dichloromethane to afford sulfone 74(Scheme 12) <2003JOC4457>.
HOOCNHCF2SO2F–CO2
–HF
–HF
N CSO2F N C OSFO
69 HN=CFSO2F
Scheme 11
ClCCF2SO2F
O
NaN3CCF2SO2F
O
F
F
N=C=O
SO2F
∆
67 68 69
N3
Scheme 10
Mg
DMF
F
F
SPh
SiMe3
F
F
SO2Ph
SiMe3
PhSCF2Br + Me3SiCl + PhSSPh
m-CPBA
CH2Cl2, 0 °C
72 73 85%
74
51%
Scheme 12
280 Functions Containing Two Halogens and Two Other Heteroatom Substituents
6.08.4 TWO HALOGENS AND TWO GROUP V ELEMENT FUNCTIONS
6.08.4.1 Two Halogens and Two Nitrogen Functions
6.08.4.1.1 Diamines and their derivatives
Representatives of this class of compounds are quite large in number. Difluoromethyldiamines,RNCF2NR1, were prepared by the addition of fluorine and cesium fluoride or chlorine to thenitrile function of cyanamides R3NC�N. Addition of SF4, F4SO, Br2, and HgF2 or Cl2 andHgF2 to the latter has produced sulfur containing amine derivatives. DihalogenodinitromethanesCX2(NO2)2 are derived from the treatment of PhI¼C(NO2)2 with Cl2, Br2, NCS or NBS,difluorodiazirine with N2O4 under UV irradiation, and Br2C(NO2)2 by reaction with ammoniaand then with chlorine. UV irradiation of polyhalogenated diamines such as (CF3)2NCF2Rproduced the corresponding difluoromethylene gem-diamines. (Me2N)2CF2 was prepared by fluor-inating tetramethylchloroformaimidinium chloride with KF in CH3CN. Bis(dialkylamino)difluor-omethanes, (R2N)2CF2, are easily available via chlorination of tetraalkyl urea derivatives withoxalyl chloride followed by the fluorination of (R2N)2CCl
+Cl� salts with KF in CH3CN or 1,3-dimethyl-2-imidazinone solutions <1995COFGT(6)249>.
Recently, bis(dialkylamino)difluoromethanes have been used as precursors for fluorinatedhexaalkylguanidinium salts. For example, the reaction of (Me2N)2CF2 75 with (dimethyl- ordiethylamino)trimethylsilanes in CH3CN afforded the salts 76 (Equation (24))<1999EUPO949226, 2002IC6118>.
F
F
NMe2
NMe2
R2NSiMe3[(Me2N)2CNR2] [Me3SiF2]
R = Me or Et
7675
+ –
ð24Þ
Previously 75 was formed by treating tetramethyl urea with COF2 in the presence of NaF<1995COFGT(6)249>. Recently a high-yield preparation of 75 involved the straightforwardfluorination of salt 77 using anhydrous Me4NF in dichloromethane (Equation (25)). Compound75 reacts with Me2NSiMe3 in CH3CN to give hexamethylguanidinium chloride, (Me2N)3C
+F�,which in turn reacts with Me3SiCF3 in monoglyme to provide easy access to (Me2N)3CCF3
<2000JFC(103)159>.
F
F
NMe2
NMe2
CH2Cl2, 0 oC(Me2N)2CCl+ Cl–
77
95%
75
+ M4NF ð25Þ
6.08.4.1.2 Cyclic compounds
In this category of compounds three-, five-, and six-membered halogenated azirine, 1,3-diazoli-dine, and 1,3,5-triazolinane derivatives are known. Difluoroazirine, for example, was prepared bythe reaction of Bu4N
+I� on F2C(NF2)2 <1995COFGT(6)249>.Halogen exchange between 2-chloro-1,3-dimethylimidazolinium chloride 78 and NaF in
CH3CN gives the difluoroimidazolidine 79 in 77% yield (Equation (26)) <1999EUP895991>. Asimilar preparation of 79 uses KF and 1,3-dimethyl-2-imidazinone as solvent in the reaction with78 (Equation (26)) <1999EUP895991, 1999EUPO949226, 2000JAP(K)200053650, 2002IC6118>.
N
NMe
Me
Cl.HCl
H
N
NMe
Me
O, 85 °C
N
NMe
Me
F
FNaF, MeCN, 80 °C
or KF,
78 79
ð26Þ
Functions Containing Two Halogens and Two Other Heteroatom Substituents 281
Difluoroimidazolidine 81 was prepared from 1,3-bis(2-methoxyethyl)-2-imidazolidinone 80 uponreaction with oxalyl chloride at 40 �C, followed by AgF in CH3CN at 50 �C (Equation (27))<2002JAP(K)2002322156>.
NN
O
OO NN OHHO
FF
80 81
i. (COCl)2, 40 °C
ii. AgF, MeCN, 50 °C ð27Þ
2-Chloro-1,3-dimethyl-2,3-dihydro-1H-benzoimidazole 82 was converted into the difluoro deri-vative 83 with KF at 85 �C (Equation (28)). Compound 83 is an efficient fluorinating agent usedto transform benzyl alcohol, at ambient temperature, into benzyl fluoride in 54% yield<2001JAP(K)2001322984>.
N
NMe
Me
H
Cl KF, 85 °C
8382
N
NMe
Me
F
F
ð28Þ
Cyclic difluoro gem-diamines 79 and 81 are efficient fluorinating agents. Compound 79 was usedin the fluorination of cyclohexanone into 1,1-difluorocyclohexane (20%) and 1-fluorocyclohexane(68%) <2002PCT0266409>, of thioester PhCS(OMe) into the a,a-difluoroether PhCF2(OMe) in89% yield <2002JAP(K)200215015>, and of 2-trimethylsiloxyoctane into 2-fluorooctane in91% yield <2002JAP(K)2002104999>. Furthermore, compound 81 converted 1-octanol inton-octylfluoride in 81% yield <2001JAP(K)2002322156>. Difluoromethane 79 when reacted with(dimethyl- or diethylamino)trimethylsilane in CH3CN at �30 �C gave (2-dialkylamino)-1,3-dimethylimidazolinium trimethyldifluorosiliconates 84 in high yield (Equation (29)) <2002IC6118>.
N
NMe
MeN
NMe
Me
F
FNR2[Me3SiF2]
R2NSiMe3
MeCN, –30 °C
8479 R = Me or Et
+ –
ð29Þ
6.08.4.2 Two Halogens and Two Phosphorus Functions
6.08.4.2.1 Bis(phosphonates)
The interest in this category of compounds rests upon (dichlorophosphonomethyl)phosphonicacid Cl2C(PO3H2)2, a substance used in the treatment of increased bone resorption and malignanthypercalcemia, and also upon the diverse biological properties of ATP analogs. A general route to(dihalogenophosphonomethyl)phosphonic acids X2C(PO3H2)2 is halogenation of appropriatetetraesters H2C(PO3R2)2 to give (dihalogenophosphonomethyl)tetraesters X2C(PO3R2)2.Although for the hydrolysis step heating in concentrated hydrochloric acid was widely used,conversion of tetraesters X2C(PO3R2)2 into silyl derivatives X2C(PO3-TMS2)2, and hydrolysiswith water was more convenient. Mixed tetraesters containing silyl esters were also synthesized inorder to selectively hydrolyze the silyl ester groups. However, little is known about selectivepreparation of partial methylbis(phosphonate esters), due to the difficulties in obtaining purecompounds having exactly one, two, or three ester substituents. Nucleoside analogs have resultedfrom the coupling of X2C(PO3H2)2 with 50-phosphoromorpholidate of adenosine. By an analo-gous manner, the CF2 analog of 30-azido-3-deoxythymidine triphosphate was obtained. Severalother nucleoside analogs were reported <1995COFGT(6)249, 1995T6805>.
A general and selective method for the synthesis of dichloromethylbis(phosphonic acid) partialalkylesters 86 and 87 from tetraesters 85 makes use of tertiary or secondary amines as dealkylatingreagents (Scheme 13) <1996TL3533>. The degree of demethylation was found to depend on
282 Functions Containing Two Halogens and Two Other Heteroatom Substituents
the type of amine and the length of the alkyl chains in the amine used. Treatment of tetraesters 85(where R1=R2=R3=R4=Me and R1=R2=Pri, R3=R4=Me) with Bu3N at 50 �C led to theformation of the corresponding partial esters 86 (where Z+ is Bu3N
+Me) in quantitative yield. Treat-ment of tetraesters 85 (where R1=R2=R3=R4=Et, Pri, or Hex) with pyridine at 115–120 �Cafforded the respective partial esters 86 (where Z+ is C5H5N
+Et, C5H5N+Pri, or C5H5N
+(n-C6H14))in 80–85% yield. Reaction of tetraesters 85 (where R1=R2=R3=R4=Me, Et, or allyl, andR1=R2=Bu or Et, R3=R4=Pri or Me) with piperidine at 105–110 �C resulted in the formationof the corresponding partial esters 87 (where Z+ is C5H10N
+H) in yields ranging from 36% to 100%.When tetraesters 85 (where R1=R2=R3=R4=Me, Et, Pri, n-C5H12, cyclopentane, or n-C6H14)were heated at 105–110 �C with morpholine, the corresponding partial esters 87 (where Z+ isO(CH2CH2)2N
+H) were formed in 20–80% yields. The mechanism of the reaction can be understoodby considering that the tetraester acts as an N-alkylating agent (Equation (30)).
PO
OR3O
R4
RNR'
RMeCN
PO
OR3O– RNR'
RR4++ ð30Þ
The synthesis of partial esters 91 uses tetraalkylesters 88 as starting materials (Scheme 14).Tetraester 88 (where R is Me) was treated with Bu3N while the other three were treated with pyridineto give ammonium salts 89. The latter are converted into the corresponding sulfonic mixed ‘‘anhy-drides’’ 90 by reaction with mesyl chloride, and then treated with aqueous base in acetone toprecipitate partial esters 91. The reaction mechanism of these products can be tentatively rationalizedas depicted in Scheme 15. The obtained ammonium cation, R3N
+R0, possesses a very powerfulelection-withdrawing effect that probably attracts the chlorine of MsCl thus facilating sulfonation atP�O�. In the resulting intermediate, the PO�R bond is additionally weakened by the MeSO2-moeityallowing easy cleavage of the PO�R bond by the chlorine anion of the ammonium salt that leadsto the product <1996TL3533>.
OR2
CP
P
OR1O
OR3
O–O
Cl
Cl
OR2C
P
P
OR1O
OR3
OR4O
Cl
Cl
O–
CP
P
OR1O
OR3
O–O
Cl
Cl
R3N
MeCN
R2NH
MeCN
Z+ Z+
Z+
86 85 87
Scheme 13
ORC
P
P
ORO
OR
O–O
Cl
Cl
ORC
P
P
ORO
OR
ORO
Cl
Cl
ORC
P
P
ORO
OSO2Me
O–O
Cl
Cl
NaHCO3, H2O
or NaOH, H2O
MeSO2ClBu3N
R R
ORC
P
P
ORO
O–
O–O
Cl
Cl
Na+
Na+
Z+ Z+
88 89 90
or pyridine
91
R = Me, Et, Pri, or n-C6H14; Z R = Bu3N Me, C5H5N Et, C5H5N Pri, or C5H5N n-C6H14
+++++
Scheme 14
Functions Containing Two Halogens and Two Other Heteroatom Substituents 283
Two nonnucleoside triphosphate analogs 96 and 97 were synthesized as substrates for terminaldeoxynucleotidyl transferase. Their preparation required activation of fluorenylmethoxycarbonyla-minoethylphosphonic acid (Fmoc–aminoethyl–phosphonic acid) 92 by 1,10-carbonyldi(1,2,4-triazole)93 in DMF and then addition of MeOH followed by bis(tri-n-butylammonium)difluoromethylene-diphosphate 94 to give ammonium salt 96 or bis(tri-n-butylammonium)dibromo-ethylenediphosphate95 to give ammonium salt 97 (Scheme 16) <2000MI1787>.
6.08.4.2.2 Cyclic compounds
Diphosphiranes (X2CP(R)P(R)) were produced by reacting ylides (Ph3P+C�X2) with Ph3P, and by
reacting trans-diphosphene (ArP�PAr) with dichloro and dibromocarbenes (CHX3) in the presenceof KOH. 1,3-Diphosphetanes X2CP(R)P(R)CX2 have been prepared by treating Cl2PCHCl2 withEt3N; by thermolysis of Me3SnP(CF3)2 gave, along with 1,3-diphosphetane F2CP(CF3)P(CF3)CF2,the trimer 2,4,6-tris(trifluoromethyl)-1,3,5-triphosphorin; and by heating Me2NP(SnMe3)CF3 at500–600 �C at 0.001 torr. 1-t-Butyl-2,4-dichloro-3,3-difluoro[1,2,4]azadiphosphetidine was preparedfrom the reaction of Cl2P(S)CF2P(S)Cl2 and butylamine <1995COFGT(6)249>.
1,2-Dihydro-1,3-diphosphetes 99 were formed as formal [2+2]-cycloaddition products by thereaction of perfluoro-2-phosphapropene 98 with phosphalkynes of the type RC�P. Instead of thenot isolable aminophosphalkynes Me2NC�P and Et2NC�P, the precursors HP¼C(F)NR2
were successfully used as synthetic equivalents (Equation (31)) <1997JOM(529)177>.
F
FPCF3
RC P
HP C(F)R PPF
F
R
CF3
+–78 °C
or
98 99
R = But, Me2N, Et2N, or Pr i2N
ð31Þ
RN
R'RRP
OO
O R
O
SO
Me Cl
PO
O
O R
SO
OMe
RN
R'RRCl–
–RClPO
O
O–
SO
OMe
RNR'
RR+
+
+–
Scheme 15
FmocNHCH2CH2P(OH)2
N NNN N
N
O
, DMF
[F2CHOP O POH]O
O–
O
[Br2CHOP O POH]
O
O– O–
O–
O
FmocNHCH2CH2P O P X P
OH
OO
OH
O
O–
O– [Bu3NH]2
i.
ii. MeOH93
iii. [Bu3NH]2
or [Bu3NH]2
92 94
95
96, X = F2C (15%) 97, X = Br2C (16%)
O
+
+
+
Scheme 16
284 Functions Containing Two Halogens and Two Other Heteroatom Substituents
Treatment of dichloromethane derivative 100 with 1 equiv. of N,N0-dimethyl-N,N0-bis(tri-methylsilyl)urea 101 at low temperature led to the formation of 1,5-diaza-2,4-diphosphorinane-6-one 102 (Equation (32)). Further reaction of 102 with another equivalent of 101 resulted in theformation of a mixture of symmetric bicyclic products 103 and 104. It was found that compound103 rearranges slowly into thermodynamically more stable 104 (Scheme 17) <1993HAC565>.
Cl
Cl PCl2
PCl2N N
O
Me3Si SiMe3
Me Me NP P
N
O
Me Me
Cl ClCl Cl
+
100 102
–2Me3SiCl
–15 °C
101
ð32Þ
The substitution of the chlorine atoms bonded to phosphorus in 102 by fluorine, alkoxy, orphenoxy groups could be realized with the formation of the corresponding P,P0-disubstitutedderivatives 105 (Equation (33)) <1993HAC565>.
NP P
N
O
Me Me
Cl ClCl Cl
NP P
N
OMe Me
R RCl Cl
102 105
R = F, MeO, EtO, PriO, or PhO
ð33Þ
When compound 102 was allowed to react with catechol, 2,3-dihydroxynaphthalene, tetrabro-mocatechol, resorcinol, saligenin, or 3,5-di-t-butylcatechol in the presence of Et3N, bridgedcompounds 106 to 110 were formed (Scheme 18). Whereas the catechol derivative 106, thenaphthol derivative 107, and the tetrabromocatechol derivative 108 could be easily obtained,the saligenin derivative 109 and the 3,5-di-t-butylcatechol derivative 110 were found to be stableonly in solution. The reaction of 102 with 1,2,4,5-tetrahydroxybenzene led to the pentacyclicderivative 111. In addition, reaction of hydroquinone with 102 afforded the polycyclic structure112 (Scheme 18) <1997HAC165>.
During the first hours, reaction between 113 and 101 produced a mixture of products 114 and115 that were found by NMR spectroscopy to be in the ratio 10:1. Isomer 114 rearranged after6 days into isomer 115 (Scheme 19) <2002ZAAC(628)1903>.
6.08.4.2.3 Miscellaneous compounds
In this category the phosphorus atoms of linear compounds R-P�CX2�P-R are substituted byvarious atoms or groups. For example, Cl2P(S)CF2P(S)Cl2 was treated with PriOH, SbF3,TMS�NMe2, and PhPCl2 to afford the corresponding derivatives (PriO)2P(S)CF2P(S)(OPri)2,
NP P
O
NMe
Cl
Cl
N NMe Me
O
NP P
N
OMe Me
Cl
Cl
N NMe Me
O
Me
–2Me3SiCl
20 °C102 + 101
Rearrangement
103 104
Scheme 17
Functions Containing Two Halogens and Two Other Heteroatom Substituents 285
F2PCF2PF2, (Me2N)2PCF2P(NMe)2, and Cl2PCF2PCl2. Dialkylphosphines R2PH reacted withmonomeric F2C¼PCF3 to give R2PHCF2PHCF3 derivatives, which upon heating with elementalsulfur afforded R2P(S)CF2PHCF3 derivatives <1995COFGT(6)249>.
Trifluoromethyl-1,3-diphosphane 117 is formed regioselectively in almost quantitative yield bythe addition of t-butylphosphane to perfluoro-2-phosphapropene 116 as a mixture of two diaster-eoisomers (Scheme 20).
Compound 117 reacts with nickel tetracarbonyl to give the binuclear complex 118 as the onlyisolable product. The mixture contains four of the eight possible isomers. One of them wasisolated in pure form by crystallization from n-pentane and its structure deciphered by X-raycrystallography (Equation (34)) <1993ZN1203>.
ClCl
P
PN N
O
Me3Si SiMe3
Me Me NP P
N
O
Me MeCl
ClCl
Cl
NP P
O
NMe
Me
Cl Cl Cl Cl
ClClCl Cl+
113 114
–2Me3SiCl
101 115
Rearrangement
Scheme 19
OOPP
N NMe
O
Me
ClCl
O
O
P
P N
NMe
O
Me
ClCl
O
O
P
P N
NMe
O
Me
ClCl
BrBr
BrBr
OOPP
N NMe
O
Me
ClCl
But
But
OOPP
N NMe
O
Me
ClCl
OO
PP
N NMe
O
MeCl Cl
OOPP
N NMe
OMe
Cl Cl
OOPP
N NMe
OMe
ClCl
OOPP
N NMe
O
Me
Cl Cl
OH
OH
OH
OH
OH
OH
Br
Br
Br
Br
OH
OH
OH
OH
OH
OH
HO
HO
OH
OH
But
But
102
106 107
108
109
110
111
112
Scheme 18
286 Functions Containing Two Halogens and Two Other Heteroatom Substituents
117Ni(CO)4 P
(OC)2NiP
P
Ni(CO)2
PF3CH
F F H
H FF
HCF3
118
–2COð34Þ
Reaction of compound 100 with catechol and Et3N led to the formation of compound 119involving two benzodioxaphospholane rings connected via a CCl2 group (Equation (35)).
Cl
Cl PCl2
PCl2 OH
OH
Et3N
OP
OC
OP
O
Cl
Cl+
100 119
ð35Þ
Reaction of 119 with 1 equiv. of tetrachloroorthobenzoquinone 120, led to the formation of amixture of 121, 122, and 123. The insolubility of isomer mixture 122/123 enabled easy separationfrom 121, but neither of the two structures could be assigned unambiguously to one isomer(Scheme 21) <1997CB1479>.
6.08.4.3 Two Halogens, a Nitrogen, and a Phosphorus Function
(E)/(Z)-2,2,4,4-Tetrafluoro-1,3-bis-trifluoromethyl[1,3]diarsetane and 2,2,4,4,6,6-hexafluoro-1,3,5-tris-trifluoromethyl[1,3,5]triarsinane were two compounds obtained when Me3SnAs(CF3)2 wasthermolyzed <1995COFGT(6)249>. Reductive debromination of N-bromodifluoromethyl-4-dimethylaminopyridinium bromide 124 with tetrakis(dimethylamino)ethene (TDAE) lead tocarbanionic species 125, which in the presence of Ph2PCl and Me3SiOTf provided the watersoluble 1-(difluorodiphenylphosphanylmethyl)-4-dimethylaminopyridinium triflate 126 in 67%yield (Scheme 22). The imidazole-N-difluoromethylanion 128 was generated in situ from1-bromodifluoromethylimidazole 127 using (Et2N)3P under Marchenko–Ruppert reaction condi-tions and trapped in the presence of Ph2PCl to afford (imidazol-1-yl)difluoromethyldiphenylphos-phine 129 in 78% yield (Scheme 23) <2001JFC(109)173>.
F
F
P
P
H
But
F3C
H
F
F
P
P
H
But
F3C
H
F
F
P
P
H
But
F3C
H
F
F
P
P
H
But
F3C
H
116 117
(R ),(R )/(S ),(S )-racemate (S ),(R )/(R ),(S )-racemate
F3CP=CF2 + ButPH2 But(H)PCF2P(H)CF3
Scheme 20
Functions Containing Two Halogens and Two Other Heteroatom Substituents 287
6.08.5 TWO HALOGENS AND ONE GROUP V ELEMENT FUNCTION
6.08.5.1 Two Halogens, a Phosphorus, and a Metalloid or Metal Function
In this category, various phosphonates and their salts such as Cl2C(TMS)P(O)(OEt)2, (TMS)(Clor F)2CP(O)(OEt)2, (Bu3Sn)F2CP(O)(OEt)2 PhHgCF2P(O)(OEt)2, (Li+ or BrCd+)�CX2P(O)(OEt)2, (BrCd+ or BrZn+)�CF2P(O)(OEt)2, and (Cd2+)[�CF2P(O)(OEt)2]2 have been synthe-sized <1995COFGT(6)249>.
The silylated phosphonate (Me3Si)CF2P(O)(OEt)2 132 was readily prepared in 92% yield bydirect silylation of (Br)CF2P(O)(OEt)2 130 using n-BuLi and Me3SiCl in THF at �78 �C<1996T165>. Under similar reaction conditions, 130 was treated at low temperature in THFwith PriMgCl (Scheme 24). This magnesium–bromine exchange reaction gave organomagne-sium compound 131 that was stable for several days at low temperature. Compound 131 is morestable than the organolithium analog (Li+)F2C
�P(O)(OEt)2 133, when by contrast the organo-cadmium (BrCd+)�CF2P(O)(OEt)2 134 and the organozinc (BrZn+)�CF2P(O)(OEt)2 135
NCF2BrMe2N
Br–
TDAENMe2N CF2
i. Ph2PCl, TDAE
ii. Me3SiOTfNCF2PPh2Me2N
–OTf
124 125 126
+++ –
Scheme 22
OP
OC
OP
O
Cl
Cl
O O
Cl
ClCl
Cl
OP
OC
Cl
Cl
OO
Cl
ClCl
Cl
OP
O
O O
Cl
ClCl
Cl
OP
OC
OP
O
Cl
ClO
O
O
O
Cl
Cl
Cl
Cl
Cl
ClCl
Cl
O
O
ClCl
ClCl
120119
121
or
122 123
Scheme 21
N
NCF2Br
N
NCF2
N
NCF2PPh2
P(NEt2)3 Ph2PCl
127 128 129
–
Scheme 23
288 Functions Containing Two Halogens and Two Other Heteroatom Substituents
compounds are stable even at room temperature. With Me3SiCl, magnesium reagent 131 wasconverted into the silylated compound 132 in 90% yield <1997JOM(529)267>. Compound 132was prepared less efficiently by electrochemical reduction of 130 in DMF and Me3SiCl, using azinc anode at a current density of 10mA cm�2 <1997JFC(85)127>.
Salt (Li+)�CF2P(O)(OEt)2 133 was used on route to prepare (a,a-difluoroalkyl)phosphonates<1993JOC6174>, 50-deoxy-50-difluoromethylphosphonate nucleotide analogs <1995JOC2563>, and1,1,6,6-tetrafluorohexane-1,6-bisphosphonic acid <2000HAC470>. Salt (BrCd+)�CF2P(O)(OEt)2134 underwent CuCl coupling with aryl iodides to give (a,a-difluorobenzylic)phosphonates<1996TL2745>. Mimetic L-4-[diethylphosphono(difluoromethyl)]phenylalanine derivatives were pre-pared from appropriately protected L-4-iodophenylalanine by esterification with diazomethane fol-lowed by a CuCl-mediated coupling with 134 <1997T11171>. Salt (BrZn+)�CF2P(O)(OEt)2 135 wasregioselectively cross coupled in a CuBr-mediated medium with methyl 2,5-diiodobenzoate<1999BMCL3109>, with various iodobenzene derivatives but with sonication <2000JCS(P1)2591>,and with �-halo-�,�-unsaturated carboxylic acid derivatives <2000JOC4888>.
6.08.5.2 Two Halogens, a Nitrogen, and a Metalloid Function
Me3SiCl was able to trap intermediate 125 followed by the exchange of fluoride for triflate ascounterion providing water-soluble 1-(difluorotrimethylsilylmethyl)-4-dimethylaminopyridinium tri-flate 136. The latter was reacted with benzaldehyde to give pyridinium triflate 137 (Scheme 25). Theimidazol-N-difluoromethyl anion 129 and 2-methyl-1-difluoromethylbenziimidazole anion 141 weregenerated using (Et2N)3P in CH2Cl2 at �70 �C under Marchenko–Ruppert reaction conditions from127 and 1-difluoromethyl-2-methylbenzimidazole 140, and then trapped by Me3SiCl to yield imida-zol-1-yltrimethylsilane 138 and benzimidazol-1-yltrimethylsilane 142 derivatives. Compounds 138and 142 were also produced from 127 and 140 by the Grobe method, that is, using Al powder inN-methylpyrrolidinone (NMP) at 20�40 �C to generate the anions 129 and 141 followed by trappingwith Me3SiCl. The heteroaryl-N-difluoromethyltrimethylsilanes 138 and 142 were quantitativelyconverted into their respective heteroarylium derivatives 139 and 143 (Scheme 26)<2001JFC(109)173, 2001SL374>.
130 131
132
Br C P(OEt)2
F
F O
ClMg C P(OEt)2
F
F O
Me3Si C P(OEt)2
F
F O
THF, –78 °C
Zn anode, 2e,Me3SiCl, DMF
40%
Me3SiCl, THF
–78 °C90%
PriMgCl
Scheme 24
125i. Me3SiCl
NCF2SiMe3Me2N
136
PhCHO
Me4NF–NCF2CMe2N
H
O– NMe4
137
ii. Me3SiOTf –OTf F–
+
+
+
+
Ph
Scheme 25
Functions Containing Two Halogens and Two Other Heteroatom Substituents 289
6.08.6 TWO HALOGENS AND TWO METALLOID FUNCTIONS
6.08.6.1 Two Halogens and Two Silicon Functions
6.08.6.1.1 Linear carbosilanes
Perchloro-1,3-disilapropane Cl2C(SiCl3)2, prepared by photochlorination of Cl3SiCH2SiCl3, wasconverted into Cl2C(SiF3)2, reduced to Cl2C(SiH3)2, and transformed into Cl2C(SiCl3) (SiMeCl2).Several other compounds in this category, for example, Cl2C(TMS)2, Cl2C(TMS) (SiMe2Cl),Cl2C(TMS) (SiMeCl2), Cl2Si(CCl2SiCl3)2, Cl2Si(CCl2SiF3)2, Cl2C(SiCl3) (SiMeCl2), F3SiCCl2-SiF2CH2SiF3, and F3SiCCl2SiF2CHClSiF3, have been prepared by various methods. Dihaloand dimethoxycarbosilanes of the general formula (XMe2Si)2 reacted with difluorocarbene togive difluoromethylsilane derivatives F2C(SiMe2X)2. Further reactions of F2C(SiMe2F)2 withGrignard and organolithium compounds have been reported <1995COFGT(6)249>.
Reaction of 1,1,1,2,2-pentamethyl-2-chloromethyldisilane 144 with AlCl3 in pentane led to therearrangement product 145 in 65% yield (Equation (36)) <1996IZV1511>. The dibromide,Br2C(SiMe3)2, was prepared on a multigram scale and in near quantitative yield by the additionof methylene dibromide to lithium diisopropylamide in the presence ofMe3SiCl at�110 �C. The use ofexcess Me3SiCl may prevent decomposition of the presumed intermediate carbenoids [LiCHBr2and BrLiC(SiMe3)2] before silylation and/or prevent C�C formation between BrLiC(SiMe3)2 andBr2C(SiMe3)2. Compound 145 was used in the chromium(II)-mediated transformation of a variety ofaldehydes into vinylbis(silanes), RCH¼(SiMe3)2 <1997JCS(P1)2279>.
Me3Si Si CCl3
Me
Me
C Si ClMe
MeClMe3Si
ClAlCl3, pentane
65%
144 145
ð36Þ
N
NCF2Br
N
NCF2
N
NCF2SiMe3
(Et2N)3P, CH2Cl2, –70 °C
Me3SiCl
127 129
138
R or Al, NMP, 20–40 °C R
R = H or Ph
RMeOTf
pentane
N
NCF2SiMe3
R
Me–OTf
139
N
NMe
CF2Br
N
NMe
CF2
(Et2N)3P, CH2Cl2, –70 °C
or Al, NMP, 20 – 40 °C
Me3SiCl N
NMe
CF2SiMe3
MeOTf
Pentane
N+
NMe
CF2SiMe3
Me–OTf
140 141
142 143
+
Scheme 26
290 Functions Containing Two Halogens and Two Other Heteroatom Substituents
Electroreduction of a mixture of ClF2C(SiMe3)2 and Me3SiCl in the THF/hexamethylphos-phoramide (HMPA) solvent system and in the presence of Bu4NBr as an electrolyte support,resulted in the formation of Me3SiCF2SiMe3 148 (anion-derived product), as major product, andMe3SiCF2CF2SiMe3 147 (radical-derived product), as minor product. Compound 148 difluoro-methylates aldehydes through the action of a difluoromethylene dianion, CF3
2�, equivalent
<1997JA1572>.Difluoromethylbis(phenyl sulfone) 146, obtained by the oxidation of PhSO2CF2SPh with H2O2,
and sulfone 74 reacts with Mg and TMSCl in DMF to produce 147 as the major product togetherwith 148 as the minor product (Equation (37)) <2003JOC4457>.
(PhSO2)2CF2
Mg, TMSiCl
DMFMe3SiCF2CF2SiMe3
F
F
SiMe3
SiMe3
74
146147 148
70%25%
79%8%
+ ð37Þ
Methylene dibromide reacts with lithium aluminum hydride (LDA) in THF at �78 �C and thenwith diphenylmethylsilyl chloride 150 gave, via the lithium salt 149, the dibromosilylmethane 151.The latter was deprotonated by LDA under the same conditions and the resulting lithium salt 152was silylated with Me3SiCl to yield the dibromodisilylmethane 153 (Scheme 27). By a similar typeof reaction, CB4 and silyl chloride 150 reacted in the presence of 2 equiv. of n-BuLi to yieldBr2C(SiMePh2)2 in 75% yield <2001CL956>.
6.08.6.1.2 Cyclic carbosilanes
In this category, representative compounds are five-membered rings 1,1,2,2,3,3,4,4,5,5-decachloro[1,3]disilolane and 1,1,2,2,3,3,4-heptachloro-5-trimethylsilanyl-2,3-dihydro-1H-[1,3]disiloleand the six-membered ring 1,1,2,2,3,3,4,4,5,5,6,6-dodecachloro[1,3,5]trisilinane. Several derivatives ofthese compounds have been synthesized and their chemistry explored <1995COFGT(6)249>.
Photobromination of trisilacyclohexane 154 with NBS in CCl4 led to the formation of amixture containing trisilacyclohexanes 155 and 156 in a ratio of 1:1 and about 10% of compound157. Isolation of 155 and further photobromination afforded 156 in 90% yield (Scheme 28).Compound 157 was obtained in 70% yield by reacting 155 with ICl and treating the intermediate158 with LiCBr3 (Scheme 29) <2000CJC1388>.
Br H
HBr
Br
HBr
–Li+LDA, THF
–78 °C
Br SiMePh2
HBr
Br
SiMePh2Br Br SiMePh2
SiMe3Br–Li+
LDA, THF
–78 °C
149 151
152153
85%
Me3SiCl
Ph2MeSiCl 150
Scheme 27
Si Si
Si
Me
Me
Me
Me
Me
Me N
O
O
BrCCl4
hν+
Si Si
Si
Me
Me
Me
Me
Me
Me
Br Br
Si Si
Si
Me
Me
Me
Me
Me
Me
BrBr
+
154 155 156 157
Br Br
Si Si
Si
Me
Me
Me
Me
CBr3
Me
Br Br
+
Scheme 28
Functions Containing Two Halogens and Two Other Heteroatom Substituents 291
6.08.7 TWO HALOGENS AND TWO METAL FUNCTIONS
Several compounds in this category are represented by the general formula X2C(SnR3)2 and areprepared by the insertion of dichlorocarbene into tin derivatives R3Sn–SnR3. However, com-pound Br2C(SnMe3)2 could also be prepared by coupling of Me3SnCBr2�TMS withMe3SnCBr2MgCl <1995COFGT(6)249>.
The reaction of Na2[Fe2(CO)8] with Br2CF2 in pentane generates (CO)3Fe(�-CO)2(�-CF2)Fe(CO)3 159. Compound 159 reacts with PPh3 with replacement of two CO ligands toform Fe2(CO)6(�-CF2)(PPh3)2 160. Both complexes 159 and 160 were characterized by singlecrystal X-ray diffraction. A simplified structure of 159 and 160 extracted from the molecularstructure is depicted below <2001ZAAC(627)1859>.
CFe FeF
FOC
OCC
C
OC COCO
CO
O
O
Fe Fe
FF
PPh3
PPh3OCOCOC CO
COCO
159
160
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Si Si
Si
Me
Me
Me
Me
Cl
Me
Br Br
155 157LiCBr3
70%
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Scheme 29
292 Functions Containing Two Halogens and Two Other Heteroatom Substituents
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2591–2599.2000JFC(102)105 Y. Guo, Q.-Y. Chen, J. Fluorine Chem. 2000, 102, 105–109.2000JFC(103)159 A. A. Kolomeitsev, G. Bissky, P. Kirch, G.-V. Roschenthaler, J. Fluorine Chem. 2000, 103,
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Functions Containing Two Halogens and Two Other Heteroatom Substituents 293
Biographical sketch
George Varvounis was born in Alexandria,Egypt, in 1953. He received his B.Sc. degreein chemistry and biochemistry in 1977 at thePolytechnic of Central London, UK, hisM.Sc. degree in applied heterocyclic chemistryin 1979 and Ph.D. degree in organic chemistryin 1982 at the University of Salford, UK. Hebecame a Lecturer at the University of Ioan-nina, Greece in 1982, an Assistant Professorin 1990, and an Associate Professor in 2001.He spent several short periods on sabbaticalleave working with Dr. G. W. H. Cheeseman atQueen Elizabeth College, University of Londonin 1983–1987, with Professor H. Suschitzky andDr. B. J. Wakefield at the University of Salford,and, with Professor J. A. S. Smith andDr. C.W.Bird at King’s College London, University ofLondon in 1988–1994. His research interestsinclude the synthesis and properties of hetero-cyclic compounds, especially benzo- andnaphtho-fused tricycles containing nitrogen,nitrogen and oxygen, or nitrogen and sulfur.
Nikolaos Karousis was born in Athens,Greece, in 1971. He received his B.Sc. degreein chemistry in 1995 and his Ph.D. degree inorganic chemistry in 2003 under the supervi-sion of Associate Professor Varvounis. Duringthe period 2000–2002 he served in the Greekarmy. He is now working as postdoctoralfellow on the synthesis of analogs of the pyr-rolo[2,1-c][1,4]benzodiazepine group of antitu-mor antibiotics.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 271–294
294 Functions Containing Two Halogens and Two Other Heteroatom Substituents
6.09
Functions Containing One Halogen
and Three Other Heteroatom
Substituents
S. V. YARLAGADDA and R. MURUGAN
Reilly Industries Inc., Indianapolis, IN, USA
6.09.1 INTRODUCTION 2966.09.2 ONE HALOGEN AND THREE CHALCOGENS 2966.09.2.1 One Halogen and Three Oxygen Functions 2966.09.2.2 One Halogen, Sulfur, and Oxygen Function 2966.09.2.2.1 One halogen and three sulfur functions 2966.09.2.2.2 One halogen, two sulfurs, and one oxygen function 298
6.09.2.3 One Halogen, Selenium, and Sulfur Function 2986.09.3 ONE HALOGEN AND TWO CHALCOGENS 2986.09.3.1 One Halogen, Two Chalcogens, and a Nitrogen 2986.09.3.2 One Halogen, Two Sulfurs, and a Phosphorus Function 2986.09.3.3 One Halogen, Two Sulfurs, and a Metal Function 299
6.09.4 ONE HALOGEN AND ONE CHALCOGEN 2996.09.4.1 One Halogen, One Chalcogen, and Two Group 15 Elements 2996.09.4.1.1 One halogen, one oxygen, and two nitrogen functions 2996.09.4.1.2 One halogen, one sulfur, and two nitrogen functions 2996.09.4.1.3 One halogen, one chalcogen, and two phosphorus functions 300
6.09.4.2 One Halogen, One Sulfur, and Two Silicon Functions 3006.09.5 ONE HALOGEN AND THREE GROUP 15 ELEMENTS 3006.09.5.1 One Halogen and Three Nitrogen Functions 3006.09.5.1.1 Halonitromethanes 3006.09.5.1.2 Miscellaneous halonitromethanes 3006.09.5.1.3 Halotriaminomethanes 3016.09.5.1.4 (Difluoroamino)fluorodiazirine 3016.09.5.1.5 Fluorine-containing diaziridines 301
6.09.5.2 One Halogen, One Nitrogen, and Two Phosphorus Functions 3016.09.5.3 One Halogen and Three Phosphorus Functions 301
6.09.6 ONE HALOGEN AND TWO GROUP 15 ELEMENTS 3026.09.6.1 Metal Halodinitromethides 3026.09.6.2 Metal Bis(phosphonyl) Halomethides 302
6.09.7 ONE HALOGEN AND ONE GROUP 15 ELEMENT 3026.09.8 ONE HALOGEN AND METALLOID FUNCTION (THREE, TWO, OR ONE, TOGETHER
WITH METALS) 3026.09.8.1 One Halogen and Three Metalloid Functions 3026.09.8.1.1 Three silicon functions 3026.09.8.1.2 Two silicons and a germanium function 3036.09.8.1.3 Two silicons and a boron function 3036.09.8.1.4 Three boron functions or two borons and a metal function 303
6.09.8.2 One Halogen, Two Metalloids, and One Metal Function 303
295
6.09.1 INTRODUCTION
The literature search done for this chapter showed that little work has been done in this area.Many subsections of the corresponding chapter in COFGT (1995) <1995COFGT(6)271> had norelevant work done during the period 1993–2003 as shown by a literature search and confirmedby a search of authors, whose groups were researching in this area. Where no literature wasfound, a summary of the work reported in the corresponding sections of COFGT (1995)<1995COFGT(6)271> is provided. In addition, we have included a summary for a better com-parison of the functional group transformations. Chalcogens is a term used for group 16 elementsor the oxygen family.
6.09.2 ONE HALOGEN AND THREE CHALCOGENS
6.09.2.1 One Halogen and Three Oxygen Functions
These functional groups are called halo orthoformates. In COFGT (1995) <1995COFGT(6)271>,halo orthoformates were made by halogenation of orthoformates or carbonates, and by displace-ment by substituted oxygen nucleophilies on carbon tetrachloride. Halogen exchange on a haloorthoformate has also been used in preparing such compounds.
Huang and DesMarteau have reported an interesting work on fluorination and reactions of afew fluoro compounds to give the fluoro orthoformates <2001JFC363, 1999CC1671>. Thereaction of bis(fluoroformyl) peroxide with fluorine in the presence of cesium fluoride or potas-sium fluoride produces FOCF2OOC(O)F in 60% yield along with a small amount ofFOCF2OOCF2OF. The hydrolysis of difluorofluoroxymethyl fluoroperformate gaveFOCF2OOC(O)OOCF2OF, which on fluorination gave the corresponding fluoro orthoformate(Equation (1)).
O
O OO
CF2OFO
FOF2C O O
O
CF2OFO
FOF2C
F OFF2 ð1Þ
6.09.2.2 One Halogen, Sulfur, and Oxygen Function
6.09.2.2.1 One halogen and three sulfur functions
The approaches to halo thioorthoformate derivatives are very similar to those used for thecorresponding oxygen compounds, halo orthoformates as shown in COFGT (1995)<1995COFGT(6)271>. However, sulfur can show more than two valencies and this leads todifferent types of halo thioorthoformates. Halo thioorthoformates can be acyclic or cyclicand the sulfur can be in sulfide, sulfoxide, or sulfone oxidation states. Halogenation ofthiocarbonates either with halogens or with sulfenyl halides leads to halo thioorthoformates.Halogen exchange can also convert one halo thioorthoformate into another halo thioortho-formate.
During the decade 1993–2003, little work was reported in this category. Senning and co-workersdescribed the reactions of sulfenyl chlorides, in particular, chloro[(4-methylphenyl)sulfonyl](phenylthio)-methanesulfenyl chloride 1, and chloro[(4-chlorophenyl)sulfonyl][(1-methylethyl)thio]methanesulfenyl chloride 2 <1998SUL19, 1999SUL73, 1994PS(86)239> withthiobenzoic acid, 4-amino-ethylbenzene, and aniline. Compound 1 is dehalogenated by potassiumiodide to a trithiocarbonate derivative (Equation (2)).
1
Me
SCO
O
PhS
ClClS
296 Functions Containing One Halogen and Three Other Heteroatom Substituents
2
Cl
SO
OCSPr-i
ClSCl
Me
SCO
O
SPhS
KI, MeCN
Me
SCO
O
SClS
Cl
Ph
1
ð2Þ
Tris(perfluoroorganochalcogenyl)methyl compounds are useful starting materials in organicchemistry. Thus (F3CS)3CCN easily undergoes hydrolysis in the presence of H2SO4 to thecorresponding amide and reacts with oxalyl chloride to give the tris(trifluoromethylthio)methylisocyanate. A number of methods are available for the synthesis of (F3CS)3CCN, however, thenucleophilic substitution of bromide in (CF3S)3CBr with silver cyanide is the most simple andconvenient of them all (Equation (3)) <1994CB449>.
(CF3S)3CBr (CF3S)3CCNAgCN ð3Þ
Tris(trifluoromethylselenyl or sulfuryl)carbenium, (CF3Z)3C+, (Z=Se or S) moieties are sui-
table synthons for the preparation of (CF3Z)3C halides <1996CB1383>. The carbenium ionsprepared by the reaction of (CF3Se)3CF with arsenic pentafluoride in liquid SO2 medium ontreatment with potassium halides provide (CF3Se)CX, (X=F, Cl, Br). The same approach is notextendable to the iodo analog as it gives the diseleno derivative and other olefinic compounds.Arsenic pentafluoride oxidizes tetra(trifluoromethylthio)methane, (F3CS)4C, to yield a stablesalt, (F3CS)3C
+ AsF6�. This salt reacts with halide ions to form halo
tris(trifluoromethylthio)methane, (F3CS)3CX (X=F, Cl, Br) as mentioned above for the equiva-lent selenium compound. In the case of iodide, it is oxidized to iodine with the formationof (F3CS)3CC(SCF3)3 <1994CB597, 1996JFC7>. Tris(trifluoromethylthio)carbonium arsenic hex-afluoride, (F3CS)3C
+ AsF6�, easily abstracts a fluorine from 2,2,4-trifluoro-4-(trifluoromethylthio)-
1,3-dithietane to give (F3CS)3CF and 2,2-difluoro-4-(trifluoromethylthio)-1,3-dithietanehexafluoroarsenate (Equation (4)).
SS
FF
FSCF3
F
F3CSF3CS
SCF3 SS
FF
SCF3++
(F3CS)3C+ AsF 6–
AsF6–
ð4Þ
Cyclic diaryliodonium salts fall under this category of halo thioorthoformate where all threesulfurs are in the sulfone form. These compounds showed generally poor reactivity towardsnucleophilic substitution reactions. This surprisingly poor reactivity of cyclic diaryliodoniumsalts with nucleophiles was solved, shedding light on its mechanism <2000CSR315>. Bozopoulosand co-workers have determined the crystal structure of 2,20-biphenyleneiodonium (methylsulfo-nyl) bis(phenylsulfonyl) methylide 3 <1994MI528>. The crystal structure of 3 showed that thetwo iodine carbon bonds and the two iodine oxygen secondary bonds to different sulfonyl groups,form a distorted planar tetragonal co-ordination around the iodine atom. Another feature ofinterest is the delocalization occurring in the carbanion and its planarity.
3
IC SS
S MeOO
OPh
O
OPh
O
Functions Containing One Halogen and Three Other Heteroatom Substituents 297
El-Sayed and co-workers have studied the effect of reaction conditions on the chlorotropicrearrangement of (1-adamantylsulfonyl) (pentachlorophenylthio)chloromethanesulfenyl chloride<1994JCS(P1)1251> (Scheme 1). The starting sulfenyl chloride gives (1-admantylsulfonyl)dichloro-methyl pentachlorophenyl disulfide if left in CHCl3 for a few days, whereas it forms S-[(pentachloro-phenylthio) dichloromethyl] adamantane-1-thiosulfonate when refluxed in ether or left standing inCHCl3 for a much longer time.
6.09.2.2.2 One halogen, two sulfurs, and one oxygen function
Halo dithioorthoformates have been obtained by the halogenation of dithiocarbonates<1995COFGT(6)271>. No new reports on the preparation of these halo dithioorthoformatesfor the review period 1993–2003 were found.
6.09.2.3 One Halogen, Selenium, and Sulfur Function
Halo selenothioorthoformates have been obtained by halogenation of diselenothiocarbonate and bythe reaction of either selenyl or sulfenyl chloride with selenothiocarbonates <1995COFGT(6)271>.No new synthetic approach has been reported during the period 1993–2003 on this class of haloselenothioorthoformates.
6.09.3 ONE HALOGEN AND TWO CHALCOGENS
6.09.3.1 One Halogen, Two Chalcogens, and a Nitrogen
These compounds, referred to as substituted halomethane derivatives, in COFGT (1995)<1995COFGT(6)271> are made by the addition of peroxides to cyanogen chloride, and by eitheraddition of diazonium salts, or adding a nitration mixture to halo diarylsulfonylmethanes. Thenitrogen part of this functional group can also be an azide. Crawford and co-workers havesynthesized the interpseudohalogen, ClCS2N3, by chlorination of cyclic pseudohalogen (CS2N3)2(Equation (5)) <1999ICA68>.
CSS
CSS
N3 N3
Cl
N3
SS
Cl2 ð5Þ
6.09.3.2 One Halogen, Two Sulfurs, and a Phosphorus Function
No new preparative methods were reported under this category in the decade 1993–2003. InCOFGT (1995) <1995COFGT(6)271>, the synthesis of halodisulfonylmethyl phosphonates byhalogenation of phosphonium salts, like triethoxyphosphonium bis(diphenylsulfonyl)methylide,was described. These phosphonates have also been prepared by nucleophilic displacement with asulfur nucleophile on trihalomethylphosphonate ester.
CCl
S
S
S ClR2
R1OO
CCl
S
S
Cl S
R1OO
R2
CCl
S
Cl
SR2
SO
O
R1
R1 = 1-Ad
R2 = C6Cl5
CHCl3,
Ether Reflux longer time
5 days
rt
rt
98%
96%CHCl3
Scheme 1
298 Functions Containing One Halogen and Three Other Heteroatom Substituents
6.09.3.3 One Halogen, Two Sulfurs, and a Metal Function
No new preparative methods for this class of compounds have appeared in the period after 1999–2003The metallo halo disulfonylmethanes reported in COFGT (1995) <1995COFGT(6)271> were pre-pared from bis(sulfonyl)halomethanes by treatment with either sodium hydroxide or by other strongbases like alkyllithiums.
6.09.4 ONE HALOGEN AND ONE CHALCOGEN
6.09.4.1 One Halogen, One Chalcogen, and Two Group 15 Elements
No preparations have been reported in the period 1993–2003 for this class of compounds, wherethe two group 15 elements are phosphorus and the chalcogen is sulfur.
6.09.4.1.1 One halogen, one oxygen, and two nitrogen functions
The most cited compounds in this category are oxaziridines. In general, the oxaziridines areprepared by the oxidation of perfluoroimines with aromatic peroxides or hydrogen peroxide. Thereaction of polynitrohalomethane with t-butyl-1-adamantane carboxylate gave an oxaziridinederivative (Equation (6)) <1994ZOR704>.
XO2N
O2N NO2t-BuO
O
ONO
O2N
X
X = -F
37–39%+
-Cl
ð6Þ
Moss and co-workers have reported the improved synthesis of alkoxychlorodiazirines<2002JPC12280> by a procedure similar to one reported by Smith and Stevens mentioned inCOFGT (1995) (Scheme 2) <1995COFGT(6)271>. A mixture of octanol, cyanamide, and anhy-drous trifluoromethanesulfonic acid was heated in chloroform under nitrogen, to give octylox-yisouronium trifluoromethane sulfonate (Step 1). This was then treated with LiCl in dimethylsulfoxide and pentane as solvent, and subsequently with sodium hypochlorite to give the octylox-ychlorodiazirine (Step 2).
6.09.4.1.2 One halogen, one sulfur, and two nitrogen functions
No synthetic method has been reported in the decade 1993–2003 for this class of compounds.Compounds reported so far in this class are either 1-chloro-1,1-dinitromethyl sulfides or sulfones.They have been prepared by chlorination of the potassium salts of dinitromethyl sulfides ordinitromethyl sulfones <1995COFGT(6)271>.
CNH
OH2N (CH2)7 Me Cyanamide
NN Cl
O (CH2)7 Me
LiCl, DMSO, pentaneStep 1
Step 2
HO-(CH2)7-Me
NaOCl
. CF3SO3HCF3SO3H
Scheme 2
Functions Containing One Halogen and Three Other Heteroatom Substituents 299
6.09.4.1.3 One halogen, one chalcogen, and two phosphorus functions
This class of compounds has been made by the Michaelis-Arbuzov reaction, between triethylpho-sphite and trichloromethyl phenyl ether <1995COFGT(6)271>. Halogenation of alkoxymethy-lene (or alkylthiomethylene) bisphosphonates also leads to this class of compounds<1995COFGT(6)271>. No new reports were found in the period 1993–2003.
6.09.4.2 One Halogen, One Sulfur, and Two Silicon Functions
There have not been any reports of the synthesis of this class of compounds in the period1993–2003. Some examples were made previously by halogenation of bis(trimethylsilyl)methylsulfides as reported in COFGT (1995) <1995COFGT(6)271>.
6.09.5 ONE HALOGEN AND THREE GROUP 15 ELEMENTS
6.09.5.1 One Halogen and Three Nitrogen Functions
6.09.5.1.1 Halonitromethanes
Halonitromethanes (one halogen and three nitro groups) are widely used as oxidants in mono-propellant fuels and in bipropellant systems with hypergolic fuels and their synthesis has beenthoroughly covered in COFGT (1995) <1995COFGT(6)271>. The simplest synthetic route forhalonitromethanes is the halogenation of trinitromethane potassium salt <1994ZOR704>.Fluoro-�-azidodinitromethane was prepared (Equation (7)) by reacting �-(difluroamino)trinitro-methane with sodium azide (NaN3) in the presence of dimethylformamide (DMF) and CH2Cl2 togive 37% yield of the desired product <1997MI324>.
CNO2
O2NO2N NF2
CF
O2N
O2N N3
NaN3, DMF, CH2Cl2
37%ð7Þ
Reaction of difluoroaminotrinitromethane with metal fluorides (KF and CsF) in DMF yields afluorodifluoroaminodinitromethane (Scheme 3). The reaction of F2NC(NO3)3 with LiBr in etha-nol or DMF affords Br(O2N)C=NF rather than the expected bromo derivative, BrF2NC(NO2)2<2001MI736>.
6.09.5.1.2 Miscellaneous halonitromethanes
Halo compounds with two nitro groups and one amino group are reported under this category.The preparation of these compounds is thoroughly covered in COFGT (1995)<1995COFGT(6)271>. Compound, FC(NO2)2NF2 behaves similarly to FC(NO2)3, with respectto stability and decomposition. The Arrhenius parameters were determined for the decompositionrates controlled by rupture of a C�NO2 bond in both the gaseous and the liquid states<1995IZV649, 2000MI234>.
NF2
O2NO2N NO2
FO2N
O2N NO2
BrO2N
O2N NF2
i
ii ii
i. KF, CsF, DMFii. LiBr, DMF
Br(O2N)C=NF
Scheme 3
300 Functions Containing One Halogen and Three Other Heteroatom Substituents
6.09.5.1.3 Halotriaminomethanes
Poly(fluoroamino)halomethanes come under this category and are used as bleaching andpyrotechnic agents. Several patents were known on these compounds, however, in the early2000s only a few reports were available in academic journals <1995COFGT(6)271>.
6.09.5.1.4 (Difluoroamino)fluorodiazirine
No new reports have been available for the preparation of this class of compounds in the reviewperiod 1993–2003. This compound was reported in COFGT (1995) <1995COFGT(6)271>.
6.09.5.1.5 Fluorine-containing diaziridines
These compounds have been reported in COFGT (1995) <1995COFGT(6)271> to be made eitherby rearrangement of fluorinated guanidines or by reductive defluorination cyclization sequence asdiscussed earlier for (difluoroamino)-fluorodiazirine. No new reports were found for the prepara-tion of these fluorine-containing diaziridines in the decade 1993–2003.
6.09.5.2 One Halogen, One Nitrogen, and Two Phosphorus Functions
No new reports have been available in the period 1993–2003 for the preparation of thesecompounds. Compounds in this class of this with two phophoryl groups and the nitrogen inthe form of either an isocyanato group or an ammonium group were reported in COFGT (1995)<1995COFGT(6)271>. The halo diphosphonylmethyl isocyanate compounds have been made bydouble nucleophilic displacement with trialkylphosphites on trichloromethyl isocyanate. Thecorresponding ammonium compound has been made by chlorination of diphosphonylmethyltrimethyl ammonium salt.
6.09.5.3 One Halogen and Three Phosphorus Functions
Blackburn and co-workers <1998CC2619, 1999PS(144)541> described the preparation ofhalogenated methanetriyl trisphosphonic acids and their esters for incorporation into analogsof adenosine 50-triphosphate <1999AG(E)1244>. They envisaged that multiplicity of anioniccharge is a major factor in protein affinity. Tetraisopropyl methylenebisphosphonate wasreacted with diethyl chlorophosphite in the presence of NaHMDS (sodium hexamethyldisilazane), followed by oxidation with iodine to give methanetriyl trisphosphonic ester(Scheme 4). The resultant ester was treated with NaOCl to give chloromethane trisphospho-nate ester, treatment with FClO3 gives the fluoro derivative (Scheme 5). Both the haloestersare hydrolyzed by trimethylsilyl bromide and Bu3N to afford the corresponding halo-substi-tuted acids, which are good in ligation of calcium ion and useful as potential bone affinityagents.
P PPriOPriO
O
OPri
O OPri
P PPriOPriO
O
OPri
O OPri
PEtO
P PPriOPriO
O
OPri
O OPri
P OEtO
i ii
i: NaHMDS, (EtO)2PCl, toluene. ii: 0.5 M I2 solution in Py-THF-H2O
OEtOEt
Scheme 4
Functions Containing One Halogen and Three Other Heteroatom Substituents 301
6.09.6 ONE HALOGEN AND TWO GROUP 15 ELEMENTS
6.09.6.1 Metal Halodinitromethides
New preparations of this class of compounds have not been reported for the period 1993–2003.Carbanions have been made from halodinitromethanes and halotrinitromethane with metals suchas potassium, silver, and mercury <1995COFGT(6)271>.
6.09.6.2 Metal Bis(phosphonyl) Halomethides
Alkali metal salts of alkylidenebis(phosphonic acid) or esters have been widely used in laundrydetergents, and have some biological applications. Little progress has been made in the decade,1993–2003, on these compounds since they were covered fully in COFGT (1995)<1995COFGT(6)271>. They are usually made from the dichloromethylene bis(phosphonicacid) ester and either a metal base or an amino base <2001WOP0121629, 1999WOP9920634>.
6.09.7 ONE HALOGEN AND ONE GROUP 15 ELEMENT
Compounds of this class were well documented in COFGT (1995) <1995COFGT(6)271>. Duringthe decade 1993–2003 no reports were found in the literature for this class of compounds.
6.09.8 ONE HALOGEN AND METALLOID FUNCTION (THREE, TWO, OR ONE,TOGETHER WITH METALS)
6.09.8.1 One Halogen and Three Metalloid Functions
6.09.8.1.1 Three silicon functions
This class of compounds, organosilanes was thoroughly covered in COFGT (1995)<1995COFGT(6)271>. A widely used procedure is the halogenation of the corresponding activedialkylmagnesium compound. For instance, the reaction of I2 and Br2 with Mg(Tsi)2(Tsi= (Me3Si)3C) gives TsiI and TsiBr, respectively. Mg(Tsi)2 was obtained by heating thelithium magnesate [Li(THF)2(�-Br)2Mg(Tsi) (THF)] in vacuum. Whereas, the TsiCl wasprepared by reacting the dialkylmagnesium with benzenesulfonyl chloride (Scheme 6)<1994JOM(480)199>.
P PPriOPriO
O
OPri
O OPri
P OEtO
P PPriOPriO
O
OPri
O OPri
P OEtO
P PPriOPriO
O
OPri
O OPri
P OEtO
P PHO–O
O
OH
O O–
POHO
P PHO–O
O
OH
O O–
POH
O–O
Cl Cl
F
i
iii
ii
ii
i. 20%NaOCl, NaHCO3, 0 °C, 1.5 h ii. TMSBr, Bu3N, CH2Cl2, reflux, overnight
iii. FClO3, NaHMDS, THF, -75 °C
OEt
OEt
OEt
F
O–
Scheme 5
302 Functions Containing One Halogen and Three Other Heteroatom Substituents
Halo tris(substituted dimethylsilyl)methane reacts with magnesium metal to form theGrignard reagent. Interestingly, the reaction of iodotris(dimethylamino-dimethylsilyl)methanewith magnesium gives the planar carbanionic center 4, without the C–Mg covalent bond<1997OM503>.
4
MgNMe2
SiMe2
CMe2Si
Me2N
I
Me2SiNMe2
6.09.8.1.2 Two silicons and a germanium function
No publication was found under this category in the review period 1993–2003. These compoundshave been reported in COFGT (1995) <1995COFGT(6)271> to be made from dihalo di(tri-methylsilyl)methane and organo germanium halide with butyl lithium as the coupling agent.
6.09.8.1.3 Two silicons and a boron function
The only compound reported in COFGT (1995) was bromo[bromobis(isopropyl)aminoboryl]bis(tri-methylsilyl)methane. This compound was made by the addition of bromine to the respective methy-lidene bis(isopropyl)aminoborane <1995COFGT(6)271>. No work was reported for this class ofcompounds in the decade 1993–2003.
6.09.8.1.4 Three boron functions or two borons and a metal function
There have not been any reports of the preparation of this class of compounds since COFGT(1995) <1995COFGT(6)271> was published. These compounds can be prepared from tetrabor-ylmethanes by the following methods: tetraborylmethanes are converted into triborylmethides ontreatment with alkyl lithiums, which on further halogenation leads to the expected final products.A similar approach was used to make the metal function containing class of compounds.Triborylmethyl halides on treatment with alkyl lithium followed by organometal halides leadsto the expected products, diborylhaloorganometallomethanes.
6.09.8.2 One Halogen, Two Metalloids, and One Metal Function
No reports have been found for this class of compounds since the publication of COFGT(1995) <1995COFGT(6)271>. These compounds have been prepared from dihalobis(trimethyl-silyl)methanes, which on reaction with alkyl lithium generates halobis(trimethylsilyl)methides.The lithium in these methides could be exchanged with other metals leading to the finalproducts.
Mg(Tsi)2 Tsi Br
Tsi I
Tsi Cl
Tsi = CTMSTMS
TMS
PhSO2Cl
Br2
I2
Scheme 6
Functions Containing One Halogen and Three Other Heteroatom Substituents 303
REFERENCES
1994CB449 R. Boese, A. Haas, M. Lieb, U. Roeske, Chem. Ber. 1994, 127, 449–455.1994CB597 R. Boese, A. Haas, C. Krueger, G. Moeller, A. Waterfeld, Chem. Ber. 1994, 127, 597–603.1994JCS(P1)1251 I. El-Sayed, V. K. Belsky, V. E. Zavodnik, K. A. Jorgensen, A. Senning, J. Chem. Soc., Perkin Trans.
1994, 1, 1251–1252.1994JOM(480)199 S. S. Al-Juaid, C. Eaborn, P. B. Hitchcock, K. Kundu, C. A. McGeary, J. D. Smith, J. Organomet.
Chem. 1994, 480, 199–203.1994PS(86)239 I. El-Sayed, M. F. Abdel-Megeed, S. M. Yassin, A. Senning, Phosporus Sulfur Silicon Relat. Elem.
1994, 86, 239–257.1994MI528 A. P. Bozopoulos, C. A. Kavounis, G. A. Stergioudis, P. J. Rentzeperis, A. Varvoglis, Z. Kristal.
1994, 209, 528–530.1994ZOR704 V. L. Medzhinski, E. L. Golod, Zh. Org. Khim. 1994, 30, 704–706.1995COFGT(6)271 A. Marinetti, P. Savignac, Functions containing one hologen and three other heteroatom substituents, in
Comprehensive Organic Functional Group Transformations, A. R. Katritzky, O. Meth-Cohn, C. W. Rees,Eds., Elsevier, Oxford, 1995, Vol. 6, pp. 271–294.
1995IZV649 V. N. Grebennikov, G. M. Nazin, G. B. Manelis, Izv. Akad. Nauk SSSR, Ser. Khim. 1995, 4, 649–651.1996CB1383 H. Alois, M. Guido, Chem. Ber. 1996, 129, 1383–1388.1996JFC7 S. Munavalli, D. I. Rossman, D. K. Rohrbaugh, C. P. Ferguson, H. D. Durst, J. Fluorine Chem. 1996,
76, 7–13.1997OM503 C. Eaborn, A. Farook, P. B. Hitchcock, J. D. Smith, Organometallics 1997, 16, 503–504.1997MI324 G. Kh. Khisamutdinov, V. I. Slovetsky, Yu. M. Golub, S. A. Shevelev, A. A. Fainzil’berg, Russ.
Chem. Bull. 1997, 46, 324–327.1998CC2619 X. Liu, H. Adams, G. M. Blackburn, J. Chem. Soc., Chem. Commn. 1998, 2619–2620.1998SUL19 F. A. G. El-Essawy, S. M. Yassin, I. A. El-Sakka, A. F. Khattab, I. Sotofte, J. O. Madsen, A. Senning,
Sulfur Lett. 1998, 22, 19–32.1999AG(E)1244 L. Xiaohai, B. Charles, G. Andrzej, S. Elzbieta, G. M. Blackburn, Angew. Chem. Int. Ed. Engl. 1999,
389, 1244–1247.1999CC1671 Q. Huang, D. D. DesMarteau, J. Chem. Soc., Chem. Commn. 1999, 17, 1671–1672.1999ICA68 M. J. Crawford, T. M. Klapotke, Inorg. Chim. Acta 1999, 294, 68–72.1999PS(144)541 X. Liu, X. R. Zhang, G. M. Blackburn, Phosphorus Sulfur Silicon Relat. Elem. 1999, 144, 541–544.1999SUL73 F. A. G. El-Essawy, A. F. Khattab, S. M. Yassin, I. A. El-Sakka, J. O. Madsen, A. Senning, Sulfur
Lett. 1999, 22, 73–84.1999WOP9920634 E. Pohjala, J. Vepsalainen, H. Nupponen, J. Kahkonen, L. Lauren, R. Hannuniemi, T. Jarvinen,
M. Ahlmark, PCT Int. Appl. WO (World Intellectual Property Organization Pat. Appl.) WO 99/20634.
2000CSR315 V. V. Grushin, Chem. Soc. Rev. 2000, 29, 315–324.2000MI234 G. M. Nazin, V. G. Prokudin, G. B. Manelis, Russ. Chem. Bull. 2000, 49, 234–237.2001JFC363 Q. Huang, D. D. DesMarteau, J. Fluorine Chem. 2001, 112, 363–368.2001MI736 G. Kh. Khisamutdinov, S. A. Shevelev, Russ. Chem. Bull. 2001, 50, 736–737.2001WOP0121629 M. Purdie, PCT Int. Appl. WO (World Intellectual Property Organization Pat.) WO 01/21629.2002JPC12280 R. A. Moss, Y. Ma, F. Zheng, R. R. Sauers, T. Bally, A. Maltsev, J. P. Toscano, B. M. Sharalter,
J. Phys. Chem. 2002, 106, 12280–12291.
304 Functions Containing One Halogen and Three Other Heteroatom Substituents
Biographical sketch
Subbarao Yarlagadda received his M.Sc. inorganic chemistry from Andhra University,Waltair, India. He obtained his Ph.D. in1991 from the Indian Institute of ChemicalTechnology (IICT), Hyderabad, India. Hisdoctoral work was chiefly on selective organictransformations by using a new class of het-erogenised homogeneous catalysts. Later, hejoined, as a postdoctoral fellow, ProfessorM. Graziani at the University of Trieste, Italyunder the UNIDO program, and worked onpolydentate ligands and their metal complexesfor an oxidative amination reaction. From1992 to 1996, he was a staff scientist in Dr.A.V. Ramarao’s group at IICT, India, andworked on the synthesis of fine and specialtychemicals, pharmaceutical intermediates byusing zeolite catalysts. In 1996, he joined Pro-fessor P. A. Jacobs at the Catholic Universityof Louvain, Belgium and worked on mesopor-ous zeolites and homogeneous catalysts forthe synthesis of specialty chemicals. SinceJuly 1998, he has worked at Reilly Industries,Indianapolis, IN, USA as a Research Associ-ate. His current interests include: the processdevelopment, invention of new routes for theexisting products, synthesis of fine and speci-alty chemicals, development of new catalystsfor the synthesis of pharmaceutical and agro-chemical intermediates, and vitamins.
Ramiah Murugan: Born in Madurai, India, heobtained his B.Sc. in 1975 from AmericanCollege and M.Sc. in 1977 from Madurai Uni-versity. After four years of working as aJunior Scientist at Madurai University, hejoined Professor A. R. Katritzky’s group atthe University of Florida, USA and obtainedhis Ph.D. in 1987. He continued there for twomore years doing postdoctoral work in thearea of high temperature aqueous organicchemistry. He joined Reilly Industries Inc.,Indianapolis, IN, USA in 1989 and is cur-rently a Senior Research Associate. Hisresearch interests include: synthesis of inter-mediates for pharmaceuticals, agrochemicalproducts, and performance products; mechan-istic studies; catalysis; polymer chemistry; andprocess development.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 295–305
Functions Containing One Halogen and Three Other Heteroatom Substituents 305
6.10
Functions Containing Four or Three
Chalcogens (and No Halogens)
A. SENNING and J. Ø. MADSEN
Technical University of Denmark, Kgs. Lyngby, Denmark
6.10.1 TETRACHALCOGENOMETHANES 3076.10.1.1 Four Similar Chalcogens 3076.10.1.1.1 Four oxygen functions 3076.10.1.1.2 Four sulfur functions 3096.10.1.1.3 Four selenium functions 3106.10.1.1.4 Four tellurium functions 311
6.10.1.2 Three Similar and One Different Chalcogen 3116.10.1.2.1 Trioxygen-substituted methyl chalcogens 3116.10.1.2.2 Trisulfur-substituted methyl chalcogens 3116.10.1.2.3 Triselenium- or tritellurium-substituted methyl chalcogens 311
6.10.1.3 Two Similar and Two Different Chalcogens 3126.10.1.3.1 Dioxygen-substituted methylene dichalcogens 3126.10.1.3.2 Disulfur-substituted methylene dichalcogens 3126.10.1.3.3 Diselenium- or ditellurium-substituted methylene dichalcogens 312
6.10.2 TRICHALCOGENOMETHANES 3126.10.2.1 Methanes Bearing Three Oxygens and a Group 15 Element, Metalloid, or Metal Function 3126.10.2.2 Methanes Bearing Three Sulfurs and a Group 15 Element, Metalloid, or Metal Function 3136.10.2.3 Methanes Bearing Three Seleniums or Three Telluriums and a Group 15 Element, Metalloid,
or Metal Function 3136.10.2.4 Methanes Bearing Three Dissimilar Chalcogens and a Group 15 Element, Metalloid,
or Metal Function 313
6.10.1 TETRACHALCOGENOMETHANES
6.10.1.1 Four Similar Chalcogens
6.10.1.1.1 Four oxygen functions
The traditional approaches to ortho-carbonates (RO)4C using chloropicrin CCl3NO2, trichloroace-tonitrile CCl3CN, cf. references <2002EUP1207147> and <2002GEP10121116>, trichloromethane-sulfenyl chloride CCl3SCl, or N-(trichloromethyl)imidocarbonyl dichloride (CCl3)N¼CCl2 as C1
donor in ortho-carbonate syntheses have been supplemented by a procedure using CS2.Monovalent and divalent alcohols (or phenols) react with CS2 in the presence of stoichiometric
amounts of CF3CO2Ag and excess Et3N to form ortho-carbonates (RO)4C in excellent yields(Equation (1)). Tetraethyl ortho-carbonate (EtO)4C is formed in 61% yield, tetraphenyl ortho-carbonate (PhO)4C in 68% yield, and the spiro compounds 1–4 in 33%, 75%, 31%, and 20%yield, respectively <1998H(48)461>.
307
CS2 + 4 ROHCF3COOAg
NEt3C(OR)4 ð1Þ
O
OO
OO
OO
OPh
Ph
Ph
Ph
O
O
O
O O
O
O
O
O
O
12
34
Heating of O,O-bis(4-chlorophenyl)iminocarbonate (4-ClC6H4O)2C(¼NH) to 180 �C gives avery low yield of tetrakis(4-chlorophenyl) ortho-carbonate (4-ClC6H4O)4C <1992JPR(334)95>.
2,2-Diphenoxy-1,3-dioxan has been prepared in 80% yield from 1,3-propanediol and dichloro-diphenoxymethane (PhO)2CCl2 <1999AJC657>. Dialkoxydichloromethanes react with alcoholsin the presence of FeCl3 to yield the corresponding ortho-carbonater <1991IZV198>.
Propylene carbonate 5 adds epichlorohydrin 6 in the presence of BF3 to form 2-(chloromethyl)-8-methyl-1,4,6,9-tetraoxaspiro[4.4]nonane 7 as a mixture of stereoisomers (Scheme 1) which upontreatment with EtONa 7 forms the corresponding methylene derivative 8 <2002MI588>. Aspirooligomer 9 is formed when pentaerythritol C(CH2OH)4 is treated with (EtO)4C at 260 �Cfor 12 h <2002JA4942>. Other bis(hydroxymethyl) compounds form spirocyclic ortho-carbonatesupon heating with (MeO)4C and acid <1992JAP04164085>. Spirocycli ortho-carbonates are alsoavialable from cyclic carbonates and oxiranes in the presence of 1-alkylpyridinium salts<1990CL2019>.
O
O
HO
HO
O
O
O
O
O
O
OH
OH
n
9
O O
O
Me
OCl+
56 7
BF3.OEt2 O
OO
OMeCl
O
OO
OMe
8
–HCl
Scheme 1
308 Functions Containing Four or Three Chalcogens
Symmetrical tetrasilyl ortho-carbonates have been prepared by heating of alkene-1,1-disilanols,such as CH2¼C(SiMe2OH)2 and (MeO)4C, in the presence of p-toluenesulfonic acid<1992JAP04169592>.
Chlorination of a solution of O,O-bis(2,2,2-trifluoroethyl)thiocarbonate (CF3CH2O)2C(¼S)and 2,2,2-trinitroethanol (O2N)3CCH2OH in 1,2-dichloroethane gives 90% yield of bis(2,2,2-trinitroethyl) bis(2,2,2-trifluoroethyl) ortho-carbonate [(O2N)3CCH2O]2C(OCH2CF3)2<1998USP5783732>.
Divinyl-substituted ortho-carbonates can be converted to the corresponding diepoxides withMCPBA <1999JAP11158182>.
6.10.1.1.2 Four sulfur functions
Spiro compounds continue to dominate the portfolio of available tetrathio-ortho-carbonates(RS)4C. Dibenzo[3,4;10,11]-1,6,8,13-tetrathiaspiro[6.6]tridecane 10 has been prepared in quanti-tative yield by heating (MeS)4C (the synthesis of which was accomplished by a modified andsomewhat improved Backer procedure involving N,N0-dinitrosoisothioureas as key intermediates)and benzene-1,2-dimethanethiol 1,2-C6H4(CH2SH)2 with acid catalysis <1997MM6721>.
10
S
SS
S
2-Methylenepropane-1,3-dithiol HSCH2C(¼CH2)CH2SH reacts with dichlorodiphenoxy-methane (PhO)2CCl2 in the ratio 2:1 to form the tetrathio-ortho-carbonate 3,9-bis(methylene)-1,5,7,11-tetrathiaspiro[5.5]undecane <1996AJC1261>.
The tetrathio-ortho-carbonates 13a–13d have been prepared from the zinc complexes 11 andthe trissulfanylcarbenium salts 12 as shown in Equation (2) <1999SM(102)1617>.
S
S
S
S
SZn
S RS
RS
S
S
S
S
S
SRS
RS
2
2 NMe4
11
S
SSMe
R1
BF4+
12
S
SS
S
S
S
S
SRS
RS
R1
13
13a, R = Me, R1 = H
13b, R = R1 = Me
13c, R, R = CH2CH2; R1 = H
13d, R, R = CH2CH2; R1 = Me
++
–
–
ð2Þ
Tetrakis(trifluoromethyl)tetrathio-ortho-carbonate (CF3S)4C has been obtained in 61% yieldfrom CBr2Cl2 and (CF3)SCu <1996JFC(76)7>.
Spirocyclic 1,4,6,9-tetrathiaspiro[4.4]nonanes are formed in very low yields (4–5%) when1,3-dithiolan-2-ones are treated with thiiranes <1996JCS(P1)289>.
A particularly neat high-yielding access to spirocyclic tetrathio-ortho-carbonates such as 16 hasbeen found in the reaction between 2H-benzo[b]thiete 14 and cyclic trithiocarbonates such as 15(cf. Equation (3)) <1997LA1603>.
Functions Containing Four or Three Chalcogens 309
S
SS
S+
S
SS
S
14 15 16
ð3Þ
The unexpectedly stable tetrathio-ortho-carbonate 18, i.e., 4,7-dichloro-2-isopropylsulfanyl-2-sulfanyl-1,3-dithiolo[4,5-c]pyridine-6-carbonitrile, was obtained (22% yield) from the reactionbetween 3,4,5,6-tetrachloropyridine-2-carbonitrile 17 and potassium isopropyltrithiocarbonate(cf. Equation (4)) <1998MI297>.
NCl
Cl
Cl
Cl
CN
Me2CHSC(=S)SK
EtOHNCl
Cl
CN
SS
SCHMe2EtO
NCl
Cl
CN
SS
HSSCHMe2
1718 19
+ ð4Þ
Following an established procedure, bis(methylsulfonyl)methane (MeSO2)2CH2 can be disulfe-nylated with N-(ethylsulfanyl)phthalimide 1,2-C6H4[C(¼O)]2NSEt to yield bis(ethylsulfanyl)-bis(methylsulfonyl)methane (EtS)2C(SO2Me)2 <2002TL1377>.
The unexpected unsymmetrical dimerization of the thiocarbonyl ylide 20, formed in situfrom PhS(¼O)2C(¼S)SC6H4Cl-4 and Me3SiCHN2, leads to tetrathio-ortho-carbonate 21, cf.Equation (5) <2003EJO813>.
C SPhSO2
4-ClC6H4S CHSiMe3
S S
Me3Si SiMe3
C
PhSO2
4-ClC6H4S
4-ClC6H4S SO2Ph20
21
– +
ð5Þ
6.10.1.1.3 Four selenium functions
Two new tetraseleno-ortho-carbonates (RSe)4C, both spiroheterocycles, have been reported.2,3,7,8-Tetramethyl-1,4,6,9-tetraselenaspiro[5.5]nona-2,7-diene 22 is formed in low yieldfrom 4,5-dimethyl-1,3-diselenole-2-selone, 4,5-methylenedithio-1,3-dithiol-2-one, and (MeO)3P<1994ZOR1009>. The structure of 22 was proven by X-ray crystallography<1995DOK(340)62>.
Se
SeSe
SeMe
Me
Me
Me
22
The reaction between the ring-strained alkyne cyclooctyne and CSe2 yields, among otherproducts, 3.3% of the yellow 4,4,5,5,6,6,7,7,8,8,9,9-dodecahydro-2,20-spirobi[cycloocta-1,3-disele-nole] 25, the main products being the triselenocarbonate 23 and the tetraselanylethene 24(cf. Equation (6)) <2000JOC8940>.
310 Functions Containing Four or Three Chalcogens
+ CSe2 SeSe
Se+
23
Se
SeSe
Se
Se
Se Se
Se+
2425
ð6Þ
6.10.1.1.4 Four tellurium functions
Tetratelluro-ortho-carbonates (RTe)4C are still unknown.
6.10.1.2 Three Similar and One Different Chalcogen
6.10.1.2.1 Trioxygen-substituted methyl chalcogens
Cyclic thio-ortho-carbonates (RO)3CSR have been prepared from dichlorodiphenoxymethane(PhO)2CCl2 and �,!-mercaptoalkanols <1999AJC657>. No seleno-ortho-carbonates (RO)3CSeRor telluro-ortho-carbonates (RO)3CTeR are on record.
6.10.1.2.2 Trisulfur-substituted methyl chalcogens
The trissulfanylcarbenium salt 26, when treated with NaBH4 in EtOH, gives a mixture of thetrithio-ortho-carbonate 27 and the trithio-ortho-formate 28 (cf. Equation (7)) <2001MI145>.
S
S
S
Me
EtO2C SMe
BF4
NaBH4
EtOH S
S
S
Me
EtO2CSMe
OEt S
S
S
Me
EtO2C SMe
26 27 28
+–
ð7Þ
Good yields of 1-oxa-4,6,9-trithiaspiro[4.4]nonanes 31 are obtained from the appropriate1,3-dithiolane-2-thiones 29 and oxiranes 30 (cf. Equation (8)) <1996JCS(P1)289>.
S S
S
R1 R2
O
R3 R4
+HBF4
.Et2O
PhCl
S
OS
SR1
R2
R3(R4)
R4(R3)
29
30 31
ð8Þ
The trithio-ortho-carbonate 19, i.e., 4,7-dichloro-2-ethoxy-2-isopropylsulfanyl-1,3-dithiolo[4,5-c]-pyridine-6-carbonitrile, has been obtained according to Equation (4) <1998MI297>.
Seleno-trithio-ortho-carbonates (RS)3CSeR and telluro-trithio-ortho-carbonates (RS)3CTeRare unknown.
6.10.1.2.3 Triselenium- or tritellurium-substituted methyl chalcogens
None of the hypothetical compound classes (RSe)3COR, (RSe)3CSR, (RSe)3CTeR, (RTe)3COR,(RTe)3CSR, or (RTe)3CSeR have been reported.
Functions Containing Four or Three Chalcogens 311
6.10.1.3 Two Similar and Two Different Chalcogens
6.10.1.3.1 Dioxygen-substituted methylene dichalcogens
A modest yield of 1,6-dioxa-4,9-dithiaspiro[4.4]nonane 32 has been obtained in the reactionbetween 2-mercaptoethanol and (PhO)2CCl2. The higher homolog 1,5-dioxa-7,11-dithiaspiro[5.5]-undecane 33 can be made from 2,2-diphenoxy-1,3-dioxan and propane-1,3-dithiol (62% yield) orfrom 2,2-diphenoxy-1,3-dithian and propane-1,3-diol (37% yield). Either reactant may also carrya methylene substituent to give the corresponding methylene-substituted spiro-ortho esters<1999AJC657>.
O
SS
O
S
S
O
O
32 33
6.10.1.3.2 Disulfur-substituted methylene dichalcogens
No further advances have occurred in this area since the publication of chapter 6.10.1.3.2 in<1995COFGT(6)295>.
6.10.1.3.3 Diselenium- or ditellurium-substituted methylene dichalcogens
Treatment of dimethyl 2-selenoxo-1,3-thiaselenole-4,5-dicarboxylate 34 with Ph3P leads to amixture of the (E )- and (Z )-diselenadithiafulvalenes 35 (cf. Equation (9)) <1980JOC2632>.
Se
SSe
MeO2C
MeO2C
Ph3P
Se
S CO2Me
CO2Me
S
SeMeO2C
MeO2C
Se
S CO2Me
CO2Me
Se
SMeO2C
MeO2C
+
34
(E )-35(Z )-35
ð9Þ
6.10.2 TRICHALCOGENOMETHANES
6.10.2.1 Methanes Bearing Three Oxygens and a Group 15 Element, Metalloid, or Metal Function
3,4-Dihydro-2,2-dimethoxy-5,5-dimethyl-1,3,4-oxadiazole 38, useful as a source of dimethoxycar-bene upon pyrolysis, has been prepared from acetone methoxycarbonylhydrazone 36 via theintermediate 37 as shown in Equation (10) <1994JA1161>. The analogous spiro compound 39has been obtained along similar lines <2002CJC1187>.
312 Functions Containing Four or Three Chalcogens
C N
Me
Me NH C
OMe
OLTA
AcOH
NN
O OAc
OMeMe
Me
MeOH NN
O OMe
OMeMe
Me
3637
38
LTA = Pb(MeCO2)4
ð10Þ
NON
O O
Ph
Me
Me
39
Tris(fluorosulfinyloxy)methyllithium [[FS(¼O)O]3C]Li has been prepared for use in lithiumbatteries <1996FRP2730988>.
6.10.2.2 Methanes Bearing Three Sulfurs and a Group 15 Element, Metalloid, or Metal Function
2,3-Dihydro-9a-(methylsulfanyl)-7-(trifluoromethoxy)thiazolo[2,3-b]benzothiazole 41 has beenprepared in three simple steps from benzothiazole 40 (cf. Equation (11)) <1999JMC2828>.
S
NS
CF3O SMe S
N
CF3O
Cl
40 41
ð11Þ
Nitrotris[(trifluoromethyl)sulfanyl]methane (CF3S)3CNO2 is formed in 45% yield upon treatmentof bis[tris[(trifluoromethyl)sulfanyl]methyl] disulfide (CF3S)3CSSC(SCF3)3 with NO2<1994CB597>.
Tris[(trifluoromethyl)sulfonyl]methyllithium [(CF3SO2)3C]Li has been prepared as startingmaterial for the corresponding fluorine compound (CF3SO2)CF <2003GEP10258577>. Thecorresponding caesium salt [(CF3SO2)3C]Cs has also been prepared <1993WOP9309092>.
6.10.2.3 Methanes Bearing Three Seleniums or Three Telluriums and a Group 15 Element,Metalloid, or Metal Function
The salt [(CF3Se)3C][AsF6] is available, inter alia, from tetrakis(trifluoromethyl) tetraseleno-ortho-carbonate (CF3Se)4C and AsF5 <1996CB1383>.
6.10.2.4 Methanes Bearing Three Dissimilar Chalcogens and a Group 15 Element, Metalloid,or Metal Function
No further advances have occurred in this area since the publication of chapter 6.10.2.4 in<1995COFGT(6)295>.
Functions Containing Four or Three Chalcogens 313
REFERENCES
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314 Functions Containing Four or Three Chalcogens
Biographical sketch
Alexander Senning was born in 1936 in Riga,Latvia. He studied chemistry in Munich,Germany (1954–1959) and Uppsala, Sweden(1960–1962). He obtained a Ph.D. in organicchemistry from Uppsala University in 1962.He joined the Department of Chemistry,Aarhus University, Denmark as assistantprofessor (1962–1965) and associate profes-sor (1965–1993). During a sabbatical leave(1973–1975), he was head of the researchlaboratory of the drug company A/S AlfredBenzon, Copenhagen, Denmark. He joinedthe Danish Engineering Academy (DIA),Lyngby, Denmark, later part of The Techni-cal University of Denmark (DTU), Lyngby,Denmark as professor of organic chemistryin 1993 until his retirement in 2003. Researchinterests: organic sulfur chemistry, medicinalchemistry. Extensive activities as book andjournal editor. A detailed chemical autobio-graphy is available in Sulfur Rep., 2003, 24,191–253.
Jørgen Øgaard Madsen was born in 1940in Aars, Denmark. He studied chemistry inAarhus, Denmark (1962–1971) and receivedan M.Sc. (1967) and a Ph.D. (1972) in organicchemistry from Aarhus University, Denmark.He held an assistant professorship at theDepartment of Chemistry, Aarhus University,Denmark (1967–1971) and joined the Depart-ment of Organic Chemistry (later Departmentof Chemistry) of the Technical Universityof Denmark (DTU) as associate professor(1972 to present). Research interests: hetero-cyclic enamines, stereospecific syntheses withbaker’s yeast, natural product chemistry,analytical organic chemistry (HPLC, MS).
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 307–315
Functions Containing Four or Three Chalcogens 315
6.11
Functions Containing Two or One
Chalcogens (and No Halogens)
W. PETZ and F. WELLER
Universitat Marburg, Marburg, Germany
6.11.1 INTRODUCTION 3186.11.2 DICHALCOGENOMETHANES 3186.11.2.1 Methanes Bearing Two Similar Chalcogens 3186.11.2.1.1 Two oxygens and a group V (15) element and/or a metalloid and/or a metal function 3186.11.2.1.2 Two sulfurs and a group V (15) element and/or a metalloid and/or a metal function 3206.11.2.1.3 Two seleniums or two telluriums and a group V (15) element and/or a metalloid
and/or a metal function 3326.11.2.2 Methanes Bearing Two Dissimilar Chalcogens 3336.11.2.2.1 Oxygen, sulfur, and two functions derived from a group V (15) element, metalloid,
and/or a metal 3336.11.2.2.2 Oxygen and selenium, or oxygen and tellurium, and two functions derived
from a group V (15) element, metalloid, and/or a metal 3346.11.2.2.3 Sulfur and selenium, or sulfur and tellurium, and two functions derived
from a group V (15) element, metalloid, and/or a metal 3346.11.3 MONOCHALCOGENOMETHANES 3356.11.3.1 Methanes Bearing One Oxygen Function and Three Functions Derived
from the Group V (15) Element, Metalloid, and/or a Metal 3356.11.3.1.1 Compounds with the OCN3 core 3356.11.3.1.2 Compounds with the OCNP2 core 3366.11.3.1.3 Compounds with the OCNSi2 core 3376.11.3.1.4 Compounds with the OCNSiTa core 3376.11.3.1.5 Compounds with the OCNB2 core 3386.11.3.1.6 Compounds with the OCPSiTa core 3386.11.3.1.7 Compounds with the OCFe3 core 3386.11.3.1.8 Compounds with the OCCo3 core 3386.11.3.1.9 Compounds with the OCNi3 core 3396.11.3.1.10 Compounds with the OCW3 core 3406.11.3.1.11 Compounds with the OCRu3 core 3406.11.3.1.12 Compounds with the OCOs3 core 3406.11.3.1.13 Compounds with the OCFe2Ni core 3416.11.3.1.14 Compounds with the OCFe2Co core 3416.11.3.1.15 Compounds with the OCFe2Rh core 3416.11.3.1.16 Compounds with the OCFe2Mn core 3426.11.3.1.17 Compounds with the OCRu2W core 3426.11.3.1.18 Compounds with the OCW2Ru core 342
6.11.3.2 Methanes Bearing One Sulfur Function and Three Functions Derived from the Group V (15)Element, Metalloid, and/or a Metal 342
6.11.3.2.1 Compounds with the SCN3 core 3426.11.3.2.2 Compounds with the SCNSi2 core 3446.11.3.2.3 Compounds with the SCPFe2 core 3456.11.3.2.4 Compounds with the SCPNi2 core 3456.11.3.2.5 Compounds with the SCPMnRe core 3456.11.3.2.6 Compounds with the SCSi3 core 3466.11.3.2.7 Compounds with the SCSi2P core 346
317
6.11.3.2.8 Compounds with the SCPSiLi core 3466.11.3.2.9 Compounds with the SCSi2Li core 3476.11.3.2.10 Compounds with the SCN2Fe core 3476.11.3.2.11 Compounds with the SCNSnPt core 3476.11.3.2.12 Compounds with the SCSiSnLi core 3476.11.3.2.13 Compounds with the SCFe3 core 3476.11.3.2.14 Compounds with the SCRu3 core 3476.11.3.2.15 Compounds with the SCOs3 core 3486.11.3.2.16 Compounds with the SCCo3 core 3486.11.3.2.17 Compounds with the SCAu3 core 3486.11.3.2.18 Compounds with the SCFe2Co core 3486.11.3.2.19 Compounds with the SCFeCo2 core 3486.11.3.2.20 Compounds with the SCCo2W core 349
6.11.3.3 Methanes Bearing One Selenium or One Tellurium Function and Three Functions Derivedfrom the Group V (15) Element, Metalloid, and/or a Metal 349
6.11.3.3.1 Compounds with the SeCN3 core 3496.11.3.3.2 Compounds with the SeCSi3 core 3506.11.3.3.3 Compounds with the TeCSi3 core 350
6.11.1 INTRODUCTION
This chapter is arranged in a manner identical with that of the corresponding chapter in COFGT(1995). At first those compounds are discussed with a group V (15) element at the carbon atomfollowed by compounds with metalloids (other main group elements), and finally by transitionmetal functionality. Compounds with dissimilar atoms at the carbon atom are arranged aftercompounds with similar atoms.
6.11.2 DICHALCOGENOMETHANES
6.11.2.1 Methanes Bearing Two Similar Chalcogens
Dichalcogenomethanes with similar chalcogens and further atoms other than chalcogens orhalogens have only been described with O2C, S2C, and Se2C; compounds with the Te2C unithad not been found up to the end of 2003.
6.11.2.1.1 Two oxygens and a group V (15) element and/or a metalloid and/or a metal function
Until 2003, compounds with the (RO)2C unit bonded to group V (15) elements other than N werenot described. Further compounds were found in which this unit is connected to silicon (O2CSi2core) and boron (O2CB2 core).
(i) Compounds with the O2CN2 core
One group of compounds with this core are urea acetals; however, the majority are spirocompounds and have been reviewed earlier by Kantlehner and co-workers in COFGT (1995).
The reaction of [C(NMe2)3]BF4 with the systemNaH/H2NMe2/B(OMe)3 produces (NMe2)2C(OEt)21 along with (NMe2)C(OEt)3, (NMe2)3C(OEt) (see OCN3 core), and Me2NCOOEt as a nonseparablemixture <2000JPR256>.
EtO
Me2N NMe2
OEt
1
318 Functions Containing Two or One Chalcogens (and No Halogens)
A series of spiro fused oxaziridines 2 and 3 were synthesized by reacting the correspondingsemicarbazone R2C¼NNHC(O)NR0(CH2)nOH (n=2, 3) with PhI(OAc)2 in CH2Cl2 or CH3OH;the compounds were separated and purified by chromatography followed by bulb-to-bulb dis-tillation; the individual compounds are collected in Table 1 <1996JA4214, 1997CJC1264,1997CJC1281>. Theoretical studies have been done on these oxaziridines <1999CJC1340>.
The compound 4 is an intermediate during the photosensitized oxidation of corresponding isotope-labeled imidazole and has been characterized by low-temperatureNMR spectroscopy<2002JA9629>.
The spirocyclic compounds 5 and 6 were obtained by silver(I) ion-mediated desulfuration–condensation reactions of carbon disulfide with the corresponding hydroxyl compounds as color-less compounds with yields of about 75% <1998H461>.
NON
O
RR
R'N N
HO OH
PhPh
3 4
O
N N
O
PhPh
5 6
O
N
O
Ph
O
N
O
Ph
N
ON
O N R'
RR
N
2
Further spiro compounds with the O2CN2 core have been reported <1997RCB(46)126,1999RCB(48)2136>.
The diazirine 7 was obtained as a solution in pentane in 70% yield in dimethylformamide(DMF) at 0 �C for 1 h (Scheme 1) <1995JFC101>.
Table 1 R and R0 of the compounds 2 and 3
2 3
Sl. no R R0 Sl. no R R0
a Me H a Me Hb Me Me b (CH2)5 Hc Me C(O)H c (CH2)5 Med Me C(O)Me d Me C(O)Phe Me C(O)C(Me)¼CH2 e (CH2)5 C(O)Phf Me C(O)Phg Me C(O)C6H4(2-OMe)h Me C(O)C6H4(4-OMe)i Me C(O)C6H4(4-NO2)j Me C(O)Mek Me SO2Ph
NN
C7F15CH2O
C7F15CH2O
NN
C7F15CH2O
Br
C7F15CH2ONa
7
Scheme 1
Functions Containing Two or One Chalcogens (and No Halogens) 319
(ii) Compounds with the O2CSi2 core
The only example of a compound with this core was described recently. The reaction of (Me2Ph-Si)2C(SMe)2 (compound 18 with the S2CS2 core) with I2 in ethyleneglycol–acetonitrile generatesthe acetal 8 in 78% yield <1996CL841>.
O
O SiMe3
SiMe3
8
(iii) Compounds with the O2CB2 core
Only one compound with this core is reported. The reaction of the dibromobis(tetramethylethy-lenedioxboryl)methane with anhydrous NaAc in methylenechloride leads to the formation of thecompound 9 in 25% yield <1974JOM(69)45>.
AcO
AcO BO
O
OB O
9
6.11.2.1.2 Two sulfurs and a group V (15) element and/or a metalloid and/or a metal function
The majority of compounds in this section involve the coordination chemistry of the adductS2CPR3 in which the two S atoms and the C atom interact with a mononuclear or dinucleartransition metal fragment in an allyl-like manner. In addition to the earlier described compoundswith the S2CPMo, S2CPW, and S2CPMn core, compounds with the cores S2CPFe and S2CPCoare also now available. The coordination mode of the S2CPR3 ligand was studied earlier.
(i) Compounds with the S2CN2 core
There are only a few compounds described in the literature with the S2CN2 core, and because ofthe different nature of the compounds a common method of preparation for these compoundscannot be formulated.
The spirocyclic compounds (10a–10e) were obtained by intramolecular ring-closure by heating theappropriate starting material in tetrahydrofuran (THF) or dimethyl sulfoxide (DMSO) as shown inScheme 2; yields and melting points are shown in Table 2 <2000SL1464>. The similar spirocycliccompound 11 was obtained in 53% yield by the reaction ofN-phenylbenzohydrazonoyl chloride withthe 5-benzylidene-3-phenyl derivative of rhodamine in CHCl3 in the presence of NEt3; the structurewas confirmed by an X-ray analysis (Scheme 3) <1999AX1877>.
S NS NH
NH
R1OO
O
R2
R1OH
HN R2
O
O
SN
N THF, ∆
S
10
Scheme 2
320 Functions Containing Two or One Chalcogens (and No Halogens)
Condensation between the 2-methylsulfanylthiazolium iodide and p-phenetidine in the presenceof NEt3 in CH2Cl2 produces the compound 12 in about 26% yield as shown in Scheme 4<2000JPR554>.
As shown in Scheme 5 the thiouracil reacts with P(OR)3 to produce the dithiaspirodione 13<1996PS(119)225>.
Various nitrilimines cycloadd to the C¼S bond of 3-phenyl-5-arylmethylene-2-thioxothiazoli-dine-4-one to give the corresponding spiro cycloadducts 14 (Ar=4-MeOC6H4, 4-MeC6H4;R=Ph, PhC2H2, PhCO, 2-naphthoyl, 2-thienoyl, Ac, EtOCO, PhNHCO) <1996PS(113)53>.The related spiro compounds 15 were formed from the nitrilimines RCN2R
1 and 3-phenyl-5-phenylmethylene-2-thioxothiazolidine-4-one (R=EtCOO, Ph, Bz, 2-thenoyl, PhNHCO, styryl,2-naphthoyl, Ac, R1=Ph, 2-thienyl) <1995JPS205>.
N
N
NNN
N
S
SO
S
O O
P(OR)3
13
Scheme 5
N
S N
S
NS
Ph
O
Ph
S
PhHN
N
ClPh
Ph
Ph
Ph
OPh
+Et3N
11
Scheme 3
SN
SN
F3C S F3CS
HNOEtI
12
-Phenetidinep+
–
Scheme 4
Table 2 Yields and melting points of the compounds 10a–10e
Nr 10 R1 R2 Yield (%) m.p. (�C)
a Me OMe 85 78–81b Me OC(Me)3 66 80–83c Me OBz 77 96–99d Me NH2 67 185–188e Et NHPh 68 134–137
Functions Containing Two or One Chalcogens (and No Halogens) 321
15
N
S NN
SO
R
Ar
Ph
Ar
N
S N
S
O
PhHCR
Ph
R1
14
(ii) Compounds with the S2CP2 core
The spiro compound 16 was reported by a Chinese working group. The compound was obtainedin excellent yield by refluxing a mixture of 1-(2-bromoethyl)-2,3-dihydro-3-propyl-1,3,2-benzodia-zaphosphorin-4(1H)-one-2-oxid with CS2 in benzene <2002CCL125>.
S
SN P
N
NP
NR O
O RO
O
R = CH2COOEt
16
A complex with this core was also prepared as shown in Scheme 6. Starting from theappropriate Cp2Zr complex, reaction with CS2 in toluene at �40 �C gave the complex 17 in 72%yield <1999OM1882>.
(iii) Compounds with the S2CSi2 core
The general method is the reaction of the corresponding (RS)2CH2 with BuLi followed byaddition of R3SiCl to give first (RS)2CH(SiR3), which is again treated with BuLi/R3SiCl togenerate the bis(dimethylphenylsilyl) ketone dithioacetal 18 in 60% yield <1996CL841>.
MeS
MeS SiPhMe2
SiPhMe2
18
A series of spiro compounds with this core containing Si�Pd and Si�Pt bonds have been described.The reaction of 2,2-bis(disilanyl)dithiane 19with Pd(CNBut)2 at room temperature or Pt3(CNBut)6 inrefluxing benzene produces the Pd complex 20 and the Pt complex 21, respectively, in 27% yield asshown in Scheme 7; 21 was characterized by an X-ray analysis <1996JOM(521)405>. The Pd
Zr P
ZrPS S
Ph
PhZr P Ph
CS2
Zr = ZrCp2
17
Scheme 6
322 Functions Containing Two or One Chalcogens (and No Halogens)
complex 20 was also described in <1996BCJ(69)289>. Cyclic organosilicon compounds 22 (R=Ph,SiMe3; R
1=H) were obtained upon bis-sylilation of RC�CR1 compounds with cyclic bis(organo-silyl)palladium intermediates <1996BCJ(69)289>.
S
S SiMe2
Me2Si R
R1
22
(iv) Compounds with the S2CSiSn2 core
Only one compound with this core was described. Compound 23 was prepared by addingbutyllithium to a stirred solution of 2-trimethylsilyl-1,3-dithiane in THF; then a THF solutionof Sn(�3-C5H5)(�-N¼C(NMe2)2) was added. Yellow crystalline blocks were obtained in 29%yield. The compound is dimeric containing a four-membered Sn�N�Sn�N ring and was char-acterized by an X-ray analysis <1995JCS(D)1587>.
Sn
N Sn
N
Me3Si S
S
S
SSiMe3
NMe2
NMe2
Me2N
Me2N
23
(v) Compounds with the S2CGe2 core
Related to the heterocycles with the S2CSi2 core, 20 and 21, the corresponding Ge-derivativeshave been prepared in a similar procedure as shown in Scheme 8. Thus, the correspondingcompound 24 reacts with Pd(CNBut)2 at room temperature to produce quantitatively the Pdcomplex 25. With Pt3(CNBut)6 in refluxing benzene the Pt complex 26 was formed in 30% yieldalong with 27 as a by-product; the compounds 25 and 27 were characterized by X-ray analyses<1996JOM(521)405>.
S
S
Si SiMe2Ph
Si SiMe2Ph
S
SPd
Me2Si
SiMe2
CNBut
CNBut
S
SPt
Me2Si
SiMe2
SiMe2Ph
SiMe2Ph
CNBut
CNBut
20
2119
Scheme 7
Functions Containing Two or One Chalcogens (and No Halogens) 323
(vi) Compounds with the S2CSn2 core
Two more compounds of this type are described in the literature. Compound 28 was preparedaccording to Scheme 9 in 94% yield by insertion of the corresponding dithiacarbene (preparedin situ) into the tin�tin bond of Me6Sn2; the compound was characterized by an X-ray structureanalysis. The related compound 29 was obtained in 48% yield by the reaction of the appropriatecarbanion with Me3SnCl <1996PAC853>.
(vii) Compounds with the S2CNa2 core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.1.2 (vi)).
(viii) Compounds with the S2CNSi core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.1.2 (vii)).
(ix) Compounds with the S2CNP core
A [3+2]-cycloaddition of an in situ generated nitrilium phosphane ylide complex with benzylN,N-dimethyl dithiocarbamate ester generates the thiaphosphirane 30 as a pale yellow oil in 13%yield as shown in Scheme 10; R denotes ubiquitous organic substituents <1999CC499>.
S
SC:
Me6Sn2
S
S SnMe3 Me3SnCl
S
S
SnMe3
SnMe3
SnMe3
SnMe3
S
S–
28
29
Scheme 9
S
S
Ge SiMe2Ph
Ge SiMe2Ph
S
S
Pd
Me2Ge
GeMe2
L
L
S
S
Pt
Me2Ge
GeMe2
SiMe2Ph
SiMe2Ph
L
L
S
S
Me2Ge
GeMe2
L
L
S
S
Pt
Me2Ge
GeMe2
L = CNBut
25
26
27
24
Scheme 8
324 Functions Containing Two or One Chalcogens (and No Halogens)
(x) Compounds with the S2CPSi core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.1.2 (viii)).
(xi) Compounds with the S2CSiGe core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.1.2 (ix)).
(xii) Compounds with the S2CSiLi core
In addition to the compounds with this core reported earlier, the solution ion pair structure of2-lithio-1,3-dithianes in THF and THF–HMPTA were studied. From low-temperature multi-NMR studies, it was found that in THF the compounds are contact ion pair species and becomeseparated ions with excess HMPTA. The compounds 31 (R=Me, Ph) were obtained from theappropriate substituted 1,3-dithianes and BuLi <1994T5869>.
S
S SiMe2R
Li
31
(xiii) Compounds with the S2CSnLi core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.1.2 (xi)).
(xiv) Compounds with the S2CPCr core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.1.2 (xii)).
(xv) Compounds with the S2CPMo core
The coordination chemistry of the adduct S2CPR3 (R=Me, Et, Cy) and various molybdenumcompounds has been explored by Miguel and co-workers. This ligand coordinates in an�3-pseudoallylic manner to one or two transition metals or to one transition metal and a maingroup element with formation of an S2CPM core. Molecular orbital (MO) analysis of the fluxionalbehavior of M(S2CPMe3)(CO)2(PMe3)2 complexes (M=Mo, W) was studied in <1996IC2406>.
The Br-bridged complex of the general formula (CO)3M0(�-Br)(�-S2CPR3)M(CO)3 (whereM
0=Reand M=Mo) was a starting complex for various other species. The complex 32 (Scheme 11, R=Cy)can be reduced with Na/Hg at �78 �C in THF to an anionic species, which by subsequentaddition of Ph3SnCl gives the yellow complex 33; on warming to room temperature, 33 is reversiblyconverted into the red compound 34 and an equilibrium of 4/5 of both complexes is reached at room
SP
Me2N
BzS
R
C N PR
W(CO)5pip
BzS(NMe2)CS
–pipCN, –W(CO)5
30
Scheme 10
Functions Containing Two or One Chalcogens (and No Halogens) 325
temperature; both compounds were studied by X-ray analyses <1999OM490>. Reduction of 35 withNa/Hg inTHFproduces the anion 36with formation of anMo�Mnbond (Scheme12).The addition ofClSnPh3 causes migration of the central carbon atom of the S2CPR3 ligand from Mo to Mn to givecompounds 37 with the S2CPMn core, which are converted into 38a–38d on addition of the ligandsdmpmor tedip. The same reaction sequence occurs, if twoCOgroups are replaced in 35by the chelatingligands dmpm or tedip to give 39a–39d and 40a–40d (see Table 3) <1995JOM(492)23>. Further, 35reacts with NaCCPh and NaCCH to give the acetylene-bridged derivatives 41 and 42, respectively, inhigh yields (Scheme 13), which were characterized by X-ray analyses <1998JA417>. The Br-bridgedcomplex 43a (M=Mo) is shown in Scheme 14; the Mo complex (see also compound 43bwith S2CPWcore) was obtained with Mo(CO)3(NCMe)3 in 90% yield. The complex 43a with the Mo�Br�Moarrangement reacts with monodentate ligands to give nearly quantitatively the related complexes 44 orwith chelating ligands to produce the complexes 45 in 60% and 80% yields, respectively. The crystalstructure of 44 (L=PEt3) is shown <1997JOM(545-546)327>.
(OC)3Re
(OC)3Re
Mo(CO)3
Mo(CO)3Mo(CO)3
S
PR3S
Br
S
PR3 PR3S
(OC)2Re
SS
CSnPh3
O
Ph3Sn
i. Na[Hg]ii. Ph3SnCl
32
3334
Scheme 11
Br
(OC)3Mn Mo(CO)3
Mo(CO)3
S
PR3
PR3
PR3
PR3
S
Mo Mn(CO)3
SS
(OC)2Mn Mo
SS
Mo Mn
SS
Br
LL
L L
(OC)3Mn
(OC)3Mn
S
PR3
PR3
S
Ph3Sn
OC COOC
CO
COPh3Sn
OC
OC
COCO
Mo
SS
LL
COCO
–
–
L L = dmpm, tedip
Na[Hg]
Na[Hg]
ClSnPh3
ClSnPh3
L–LL–L
35
36
37
3839
40
Scheme 12
326 Functions Containing Two or One Chalcogens (and No Halogens)
Reactions of 35 with Br bridge replacement are depicted in Scheme 15. The reaction of 35with NaOMe in methylenechloride generates 46 in about 80% yield containing an OMe bridgeinstead of a Br bridge. The OMe bridge can easily be replaced by carbon acids to produce therelated complexes 47 in yields between 30% and 60%, while the action of ethanolamine generates
Br(ON)(OC)2Mo Mo(CO)2L
S
PR3S
Mo
SS
Br LL
COCO
(ON)(OC)2Mo
(ON)(OC)2Mo
M(CO)3
SS
Br
NO
Mo
Br
OC
OC
S
SPCy3
PCy3
PCy3
M(CO)3(NCMe)3
L L–L
L = PEt3 L = P(OMe)3
L–L = Me2PCH2PMe2L–L = Ph2PCH2PPh2
43 (a, M = Mo;
b, M = W)
44 45
Scheme 14
(OC)3Mn Mo(CO)3
S
PR3
PR3
S
Br
NaCCPh
NaCCH
(OC)3Mn Mo(CO)3
S
PR3S
C
CPh
(OC)3Mn Mo(CO)3
SS
C
C
Mn(CO)3(OC)3Mo
S
R3P S
R = Cy
35
41 42
Scheme 13
Table 3 R and chelating ligand of thecompounds 38, 39, and 40a–40d
38, 39, 40 R L–L
a Cy tedipb Pri tedipc Cy dmpmd Pri dmpm
Functions Containing Two or One Chalcogens (and No Halogens) 327
48 in 46% yield. The S-bridged complex 49 was obtained by the reaction of 35 with the salt[HSCH2CH(COOMe)NH3]Cl in 41% yield; most of the complexes were studied by X-ray analysis<2002OM2979>.
Replacement of the Br bridge by other ligands starting from the dinuclear complex 35 (R=Pri)is also shown in Scheme 16. Thus, Na/Hg reduction generates the anion 36, which can beconverted with PhSeI in THF into red crystals of 50 (82% yield, crystal structure). Similarly, with
(OC)3Mn
(OC)3Mn
Mo(CO)3 Mo(CO)3
S
PCy3 PCy3 PCy3
PCy3PCy3S
Br
NaOMe(OC)3Mn
SS
OMe
Mo(CO)2 Mo(CO)2 Mo(CO)2
SS
O
(OC)3Mn (OC)3Mn
SS
O
SS
SH
O
NR2 NH2NH2
COOMeR1 R2
R1 R2 R
H Me H
H Ph H
H Bz H
Me Me H
H H Me
46
47 48 49
35
Scheme 15
(OC)3Mn
(OC)3Mn
(OC)3Mn
(OC)3Mn
(OC)3MnMo(CO)3
Mo(CO)3 Mo(CO)3
Mo(CO)3
S
PR3
PR3
PR3
PR3
PR3
PR3S
Br
SS
–
Na[Hg]
Ph2PCl
SS
SePh
SS
P
Ph Ph
(OC)3Mo
SS
Mn(CO)3Mn(CO)3
SS
P
Ph Ph Ph3Sn
Ph3SnCl
PhSeI
CH2Cl2, reflux
3536
50 51
5253
Scheme 16
328 Functions Containing Two or One Chalcogens (and No Halogens)
Ph2PCl, brown crystals of 51 (76% yield) were obtained which on heating rearrange and give 52with the S2CPMn core in 86% yield. Heating of 36 and addition of Ph3SnCl rearranged to give53, which was confirmed by an X-ray analysis <1994OM4667>.
(xvi) Compounds with the S2CPW core
MO analysis of the fluxional behavior of M(S2CPMe3)(CO)2(PMe3)2 complexes (54, M=Mo, W)was studied in <1996IC2406>.
S PMe3
MPMe3OC
CO
SPMe3
54
The dinuclear nitrosyl complex 43b (M=W) with an Mo�Br�W arrangement was obtained in86% yield by the reaction of (CO)2(NO)BrMo(S2CPPCy3) with W(CO)3(NCMe)3 in THF asshown in Scheme 14; for the related Mo complex, see compounds with the S2CPMo core<1997JOM(545-546)327>.
Cationic carbyne complexes with this core are also described. As shown in Scheme 17, twoCO groups and MeCN are replaced in the starting carbyne complexes (n=1, 4) by the reactionwith S2CPCy3 for 24 h in MeOH at room temperature; the compounds 55 were obtained in 90%yield; the complex with n=1 was characterized by an X-ray analysis <1997OM4099>.
(xvii) Compounds with the S2CPMn core
Compounds with this core are only known with the S2CPR3 ligand bonded in an �3-mannerand bridging two transition metals. As depicted in Scheme 18, the neutral complexes 56(M=Mn) and 57 (M=Re) can be reduced with Na[Hg] to produce anionic species (structurenot reported), which undergo protonation reactions <1998OM3448>. For further compoundswith an S2CPMn core, see migration of the central carbon atom from Mo to Mn to give 37and 38 as shown in Scheme 12 <1995JOM(492)23> and the compounds 52 and 53 inScheme 16 <1994OM4667>.
(xviii) Compounds with the S2CPRe core
For an Re complex with this core, see also compound 57 in Scheme 18. The complexes 58(R=Cy, Pri) were obtained in about 55% yield by heating the appropriate S2CPR3 bridged
WCP P
H
(CH2)n
MeCNCO
COS PCy3
WCP P
S
H
(CH2)n
[BF4][BF4]
S2CPCy3
55
Scheme 17
Functions Containing Two or One Chalcogens (and No Halogens) 329
dinuclear octacarbonyl compounds in octane or toluene at reflux temperature during conversionof the ligand from an �2- into an �3-coordination, as shown in Scheme 19; the cyclohexyl derivativewas confirmed by an X-ray analysis <1997CB1507>. The preference of �3-Mn coordination over�3-Re coordination in an MRe(CO)6(�
3-S2CPR3) complex has been studied <1999OM490>.
(xix) Compounds with the S2CPFe core
Mononuclear complexes with this core have been described by Miguel and co-workers as depictedin Scheme 20. The complex 59 (R=Cy, Pri) could be obtained in 40% yield by reactingFe(BDA)(CO)3 with S2CPR3 in CH2Cl2 solution. The complex with R=Cy was characterizedby an X-ray structure analysis. Alkylation with CF3SO3Me produced the corresponding cationiccomplexes 60; a crystal structure of 60 (R=Cy) was obtained <1996OM2735>.
(xx) Compounds with the S2CPCo core
The first compounds with an S2CPCo core are reported (Schemes 21 and 22). Starting fromvarious Mn or Re complexes with the chelating S2CPR3 ligand, with Co2(CO)8 or Na[Co(CO)4] avariety of mixed dinuclear complexes (61a–61d) with Co�Mn and Co�Re bonds are obtained inabout 80% yield; an X-ray analysis was performed on 61 (M=Mn, R=Cy). The preparation ofthe complexes 62 with an allylic ligand and Mo�Co and W�Co bonds from the related mono-nuclear complexes and Co2(CO)8 are depicted in Scheme 22; the structure of the complex 62with M=Mo and R=Cy was confirmed by an X-ray analysis <1994OM2330>.
S
FeCOOC
CO
S
Me +
S PR3 PR3
FeCOOC
CO
S CF3SO3MePh O
Me
FeCOOC
CO
S2CPR3
59 60
Scheme 20
Toluene, reflux
(OC)3Re Re(CO)3
S
PR3S
58Re = Re(CO)4
Re Re
S
PR3
S
Scheme 19
(OC)3M M(CO)3
S
PR3S
[M2(CO)6(S2CPR3]2–Na[Hg]
M R56, Mn Cy56, Mn Pri57, Re Cy
Scheme 18
330 Functions Containing Two or One Chalcogens (and No Halogens)
(xxi) Compounds with the S2CPNi core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.1.2.(xvi)).
(xxii) Compounds with the S2CPPt core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.1.2.(xvii)).
(xxiii) Compounds with the S2CFe2 core
The reaction of the cationic complex cis-[Cp2Fe2(�-CS)(�-CSMe)(CO)2]+ with Na[S2CNMe2] affords
the dithiocarbene complex 63 along with a carbyne complex <2002JOM(659)15>. With nucleophilesRS� (R=Me, Ph, CH2Ph), the related �-carbene complexes 64 were obtained <1989OM521>.
Cp(OC)Fe Fe
CS
MeS
S
NMe2
Cp
63
S
M Co(CO)2
SS
Br
M
CO
S
SOCPR3
PR3
Co2(CO)8
COOC
M Ra Mo Cyb Mo Pri
c W Cyd W Pri
62
Scheme 22
(OC)3M Co(CO)2
SS
Br
M
CO
S
S
OC
OCPR3
PR3
PR3
Br
Re
CO
S
S
OC
OC
Co2(CO)8
Na[Co(CO)4]
M RMn Cy
b Mn Pri
c Re Cyd Re Pri
M RMn CyMn Pri
Re CyRe Pri
61
a
Scheme 21
Functions Containing Two or One Chalcogens (and No Halogens) 331
Cp(OC)Fe Fe(CO)Cp
SR
CO
MeS
64
(xxiv) Compounds with the S2CFeCo core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.1.2.(xix)).
(xxv) Compounds with the S2CCoRu core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.1.2.(xx)).
6.11.2.1.3 Two seleniums or two telluriums and a group V (15) element and/or a metalloidand/or a metal function
(i) Compounds with the Se2CSi2 core
A series of bicyclic compounds containing Se�Se bonds have been described, which wereobtained by the reaction of bis(silyldiazamethyl)polysilanes with elemental Se. Thus, Se-bridgedsix-membered rings (65a–65b) and seven-membered rings (66a–66c) were reported <1996G147>.
65a
65b
Me2Si
Me2Si Se
Se
Se
Se
SiMe2
SiMe2
SiMe2
Se
SiMe2Ph
Se
SiMe3
Me2Si
Me2Si Se
SeSe
SiMe3
SiMe3
Se
Se
SiMe2
SiMe2
SiMe2
Se
SiMe2Ph
PhMe2Si
Se
Se
SiMe2
SiMe2
SiMe2
Se
SiMe3
Me3Si66a
66b 66c
(ii) Compounds with the Se2CSiLi core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.1.3.(ii)).
332 Functions Containing Two or One Chalcogens (and No Halogens)
(iii) Compounds with the Se2CPPd core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.1.3.(iii)).
6.11.2.2 Methanes Bearing Two Dissimilar Chalcogens
Dichalcogenomethanes with dissimilar chalcogens and further atoms other than chalcogens orhalogens are known with the OSC and SSeC units.
6.11.2.2.1 Oxygen, sulfur, and two functions derived from a group V (15) element, metalloid,and/or a metal
(i) Compounds with the OSCN2 core
The spirocyclic compounds (67a–67e) were obtained via a one-flask reaction of the corresponding1,2-diaza-1,3-butadienes with oxazolidine-2-thion in THF at room temperature as shown inScheme 23; yields and melting points are shown in Table 4 <2000SL1464>.
(ii) Compounds with the OSCSi2 core
The O,S-acetal (Me3Si)2C(OMe)(SPh) 68 was obtained by reacting methoxy(phenylthio)-methane with BusLi in THF in the presence of TMEDA followed by addition of Me3SiCl<1986JOC879>; reactions of the compound are described in <1998SC1415, 1998ACS1141>.
MeO
MeS SiMe3
SiMe3
68
The preparation of this fluoro-substituted benzoxathiol–1,1-dioxide 69 was described in<1996AP(329)361>.
S NO NH
NH
R1OO
O
R2
OR1
N NR2
O
O NHO
S
67
Scheme 23
Table 4 Yields and melting points of the compounds 67a–67e
Nr 67 R1 R2 Yield (%) m.p. (�C)
a Me OMe 69 147–150b Me OC(Me)3 78 126–128c Me OBz 67 105–108d Me NH2 79 180–185e Et NHPh 80 145–148
Functions Containing Two or One Chalcogens (and No Halogens) 333
O
SO
OSiMe3
SiMe3
MeO
F
69
(iii) Compounds with the OSCSiGe core
Treatment of HC(SPh)(GeMe3)(OMe) with BuLi in THF solution at �78 �C followed by additionof Me3SiCl in THF produced the compound (Me3Si)C(SPh)(GeMe3)(OMe) 70 in 90% yield<2000JCS(P1)2677>.
MeO
PhS GeMe3
SiMe3
70
(iv) Compounds with the OSCGe2 core
Treatment of HC(SPh)(GeMe3)(OMe) with BuLi in THF solution at �78 �C followed by additionof Me3GeCl in THF produced the compound C(SPh)(GeMe3)2(OMe) 71 in 46% yield; the use ofMe3GeBr increased the yield to 92% <2000JCS(P1)2677>.
MeO
PhS GeMe3
GeMe3
71
(v) Compounds with the OSCSiLi core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.2.1.(iii)).
6.11.2.2.2 Oxygen and selenium, or oxygen and tellurium, and two functions derivedfrom a group V (15) element, metalloid, and/or a metal
Compounds with OSeC or OTeC fragments with adjacent group V elements, metalloids ortransition metals have not yet been described and no further advances have occurred in thisarea since the publication of COFGT (1995) (chapter 6.11.2.2.2).
6.11.2.2.3 Sulfur and selenium, or sulfur and tellurium, and two functions derivedfrom a group V (15) element, metalloid, and/or a metal
(i) Compounds with the SSeCSiLi core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.2.3.(i)).
334 Functions Containing Two or One Chalcogens (and No Halogens)
(ii) Compounds with the SSeCFe2 core
The only compound in this series is reported by Angelici and co-workers and it contains thecarbene ligand CSR(SeR0) coordinated at a metal in a bridged manner. Thus, the reaction of thechemically generated radical [Fe2Cp2(CO)2(�-CSMe)]_with PhSeSePh in THF solution at �20 �Cproduced the carbene complex 72 in 31% yield <1986JA3688>. The complex is also obtained byreacting the cationic complex [Fe2Cp2(CO)2(�-CSMe)]_+ with the nucleophile PhSe�; see alsocompounds with the S2CFe2 core <1989OM521>.
Cp(OC)Fe Fe(CO)Cp
SePh
CO
MeS
72
(iii) Compounds with the SSeCPPd core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.2.2.3.(ii)).
6.11.3 MONOCHALCOGENOMETHANES
The majority of compounds in this section contain a �3-CER carbyne ligand (E=chalcogen)bridging a triangular face of a transition metal cluster compound. R can also be a 16- or17-electron transition metal fragment, e.g., C5H5Fe(CO)2, Mn(CO)5, etc. In this case the CEunit can be considered as �4-bridging. Not included are cluster compounds in which only the16-electron ligand CE coordinates at an appropriate trinuclear cluster in a �3-manner.
The bonding of a CER fragment to the main group elements is restricted to a few examplesbearing mainly the OCN3 core.
The compounds are arranged in a manner that the CER fragment (E=chalcogen) is bonded tothree identical main group elements, mixed main group elements, mixed main group transitionmetal elements, three identical transition metal elements, and different transition metal elements.
6.11.3.1 Methanes Bearing One Oxygen Function and Three Functions Derivedfrom the Group V (15) Element, Metalloid, and/or a Metal
6.11.3.1.1 Compounds with the OCN3 core
The reaction of [C(NMe2)3]BF4 with the system NaH/H2NMe2/B(OMe)3 produces (NMe2)3C(OEt)73 along with (NMe2)2C(OEt)2 1, (NMe2)3C(OEt) and Me2NCOOEt as a nonseparable mixture;similar for (NMe2)3C(OEt) 74 <2000JPR256>.
EtO
Me2N NMe2
NMe2
73
MeO
Me2N NMe2
NMe2
74
The compound 75 was obtained in 90% yield by the reaction of the related ionic triazolederivative with methanol in the presence of K2CO3; the related compound 76 was detected during
Functions Containing Two or One Chalcogens (and No Halogens) 335
the thermolysis of CF3C(O)N¼C(NPri2)OCOCF3 and characterized by NMR studies; seeScheme 24 <1997JOC9070>.
The compounds 77 (R=H, Ac) were obtained from hydrolysis of the corresponding imidazo-lones as shown in Scheme 25 <1996JCS(P2)371>. The compound 77 (R=H) was also obtainedin 18% yield from a photosensitized oxidation process of the corresponding guanidine compound<1999EJOC49>; see also <1998JA10283>.
The preparation of various heterocyclic compounds were reported; the compounds 78 wereobtained by the reaction of the appropriate nitrone with RCNX compounds in CH2Cl2 in70–90% yield (X=O; R=ClCH2CH2, a-naphthyl; X=S, R=Ph) <2001RCB882>. The tri-azine 79 was obtained as a by-product (15% yield) during the reaction of [C(NH2)3]Cl withC3F7CF¼NC4F9 in MeCN in the presence of NEt3 <2001RCB476>.
N
ON
NO R
Ph X
78
N
N
N
NOH
C3F7 C3F7
C3F7C3F7
79
N
6.11.3.1.2 Compounds with the OCNP2 core
The phosphonic acid derivative 80 was used as a biochemical inhibitor; no preparation was given<2001BBR(287)468, 1999BJ(337)373>. The related compounds 81 were used as compoundsinteracting with HIV-1 reverse transcriptase <2001MB(35)717>.
N
HN
O NH
HN O
RO
RO
N
O
O NH
O
RO
RO
H2NH2N
77
Scheme 25
N
N
NN
N
N
NPr2 NPr2
NPr2
NPr2
NPr2
NPr2
Pr2N Pr2NSO2CF3 SO2CF3
SO2CF3
+
–
MeO
N
O
N
F3COCO
CF3NF3C
F3C
O OCOCF3
75
76
i
i
i
i
i
i
Scheme 24
336 Functions Containing Two or One Chalcogens (and No Halogens)
(HO)2OP
HO PO(OH)2
HN
SPh
80
(HO)2P
HO P(OH)2
HN
N
OH
OR
O
O
81
R = PO(OH)2, H
6.11.3.1.3 Compounds with the OCNSi2 core
Compounds with this core are shown in Scheme 26 and have been obtained from theappropriate benzotriazole in various yields together with other products by the reaction withlithium diisopropylamide (LDA) and trimethylsilyl chloride at �78 �C. Exhaustive silylation leadsto 82 with yields up to 86%. Silylation of 83 produces 82 in high yields <1999T11903>; thepreparation of 83 was also described in an earlier report <1995TL6321>.
The four-membered ring compound 84 was obtained in 52% yield by the photochemically inducedaddition of MeOH on the corresponding trisilacyclobutanimine (Scheme 27) <1992JOM(441)185>.
6.11.3.1.4 Compounds with the OCNSiTa core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.1.2).
OMeNH
PhR2Si R2Si
R2Si
R2Si
SiR2
SiR2NPh
MeOH
R = But
84
Scheme 27
NN
N
R
NN
N
R
NN
N
R
Me3Si
Me3SiSiMe3
SiMe3
SiMe3
LDA, TMSCl LDA, TMSCl
R = OMe, OCD3, OPh, OC2D5
82
83
Scheme 26
Functions Containing Two or One Chalcogens (and No Halogens) 337
6.11.3.1.5 Compounds with the OCNB2 core
Only one compound with this core is described. The reaction of the three-membered ringcompound NB2R3 (R=But) at �78 �C with CO produces the tricyclic spiro compound 85 asdepicted in Scheme 28 <2002ZAAC1631>.
6.11.3.1.6 Compounds with the OCPSiTa core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.1.3).
6.11.3.1.7 Compounds with the OCFe3 core
The related section in chapter 6.11.3.1.4 in COFGT (1995) includes compounds in which the�3-bonded COR group bridges the face of a triangular cluster or one face of a tetrahedral cluster,contributing three electrons to the number of 48 or 60 CVE, respectively. Only one new exampleof a triangular cluster has been described.
The trinuclear complex 86 (NR2=NBut(SiMe3), X=Cl) was obtained in 62% yield by thereaction of [Fe3(CO)11]
2� with Cl2BNBut(SiMe3) in benzene <1999EJIC2277>.
(OC)3FeFe(CO)3
Fe(CO)3
O
B
X
NR2
O
BR2N
X
86
6.11.3.1.8 Compounds with the OCCo3 core
This section contains compounds that are based on the trinuclear cluster Co3(CO)9(�3-COR), inwhich R represents various organic substituents including main group or transition metal ele-ments. Starting materials are mainly Co2(CO)8, MCo(CO)4, or the covalent trinuclear clusterCo3(CO)9(�3-COLi).
Thus, the reaction of NaCo(CO)4 with (acac)3ZrCl in toluene generates the complex [(acac)3-Zr-OCCo3(CO)9] 87 in 60% yield <2000JOM(604)68>. The similar reaction with AlCl3 inbenzene gave [(THF)3AlOCCo3(CO)9{Co4(CO)13}] 88 <1994ZN(B)1549>. The mixed salt
O
RB O
BRRB
RN
NR
BRRNRB
BRCO
85R = But
Scheme 28
338 Functions Containing Two or One Chalcogens (and No Halogens)
[Et4N][Cl2SiOCCo3(CO)9{Co4(CO)11}] 89 was prepared as a minor compound during the reactionof Si2[Co2(CO)7]2 with [Et4N][Co(CO)4] <1992AX(C)1204>. All the compounds were character-ized by X-ray analyses.
CoCo
Co
O
Co = Co(CO)3
Zr(acac)3
87
CoCo
Co
O
Co
Co Co
OAlTHF
THFTHF
Co = Co(CO)3
Co
O
88
CoCo
Co
O
SiCl
Cl
Co = Co(CO)3
Co1
Co1 = Co4(CO)11
-
89
6.11.3.1.9 Compounds with the OCNi3 core
The reaction ofK[CpNiCO] in toluene with a series of boron compounds of the type ClB(NR2)X leadsto the trinuclear Ni cluster compounds 90 (a: NR2=NBut(SiMe3), X=Cl; b: NR2=N(SiMe3)2,X=Cl; c: NR2=NMe2, X=BNMe2Cl) in low yields of about 15% <1999EJIC2277>.
CO
CpNiNiCp
NiCp
O
B
X
NR2
90
Functions Containing Two or One Chalcogens (and No Halogens) 339
6.11.3.1.10 Compounds with the OCW3 core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.1.6).
6.11.3.1.11 Compounds with the OCRu3 core
Two new compounds with this core were prepared. Starting from [Ru3H3(CO)9(�3-COMe)],addition of the appropriate Au complexes [Au{�-Ph2P(CH2)nPPh2}Me2] (n=1, 5) in ether gavethe mixed-metal cluster complexes 91 and in about 30–40% yield; both compounds were char-acterized by X-ray analyses <1998JCS(D)1107>.
PAu
RuRu
Ru
O
H
Ru = Ru(CO)3
AuP
OC
OC
P
91
P = PPh2(CH2)nPPh2; n = 1, 5
In <1995OM481> the tetranuclear cluster [Ru3Pt(�-H)(�3-COMe)(CO)10(PR3)] 92 isdescribed, obtained from the reaction of [Ru3(�-H)(�-COMe)(CO)10] with PtPR3(nb)2(R=Cy, Pri), but according to the crystal structure, the carbyne group COMe is asymmetri-cally bonded directing to a �-bridging group (two short Ru�C bonds, 199 and 197 pm and onelong bond, 260 pm).
RuRu
Ru
O
Ru = Ru(CO)3
PtH
R3PCO
92
6.11.3.1.12 Compounds with the OCOs3 core
The anionic complex 93 was obtained as yellow crystals from the reaction of[Os3H3(CO)9(�3-COMe)] with 1,5-diazabicyclo[5.4.0]undec-5-ene (DBU) in CH2Cl2 in 87%yield. Further reaction with [AuPPh3]Cl/TlPF6 gave the cluster compound 94 in 85% yieldas depicted in Scheme 29 <1992JCS(D)1701>. The hexanuclear cluster 95 was obtainedin 32% yield from the reaction of [Os6(CO)16(MeCN)2] with 1 equiv. of pyridine in
340 Functions Containing Two or One Chalcogens (and No Halogens)
CH2Cl2 solution at room temperature; the cluster was characterized by an X-ray analysis<1997JCS(D)4357>.
Os(CO)2
Os
py(OC)2OsOs
O
Os
Os(CO)2(py)2
Os = Os(CO)3
95
6.11.3.1.13 Compounds with the OCFe2Ni core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.1.9).
6.11.3.1.14 Compounds with the OCFe2Co core
The cluster 96 was obtained in 62% yield by addition of HgPh2 to a solution ofFe2Co(H)(�-COMe)(CO)7Cp in toluene; the compound was characterized by an X-ray analysis<1992OM540>.
6.11.3.1.15 Compounds with the OCFe2Rh core
For the structure of the Rh cluster 97 with this core, see the related Co cluster 96. The cluster wasobtained in 55% yield by addition of HgPh2 to a solution of Fe2Rh(H)(�-COMe)(CO)7Cp intoluene; the compound was characterized by an X-ray analysis <1992OM540>.
OsOs
Os
O
H
HOs
Os
Os
O
H
H
H
OsOs
Os
O
H
H
AuPh3
Os = Os(CO)3
–
93
94
Scheme 29
Functions Containing Two or One Chalcogens (and No Halogens) 341
(OC)CpMFe
Fe
O
MCp(CO)Fe
Fe
O
Hg
Fe = Fe(CO)3
96 (M = Co)97 (M = Rh)
6.11.3.1.16 Compounds with the OCFe2Mn core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.1.12).
6.11.3.1.17 Compounds with the OCRu2W core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.1.13).
6.11.3.1.18 Compounds with the OCW2Ru core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.1.14).
6.11.3.2 Methanes Bearing One Sulfur Function and Three Functions Derived from the Group V(15) Element, Metalloid, and/or a Metal
The compounds in which two or three different elements are attached to the SC carbon atomare rare and only realized in some examples. Main group compounds concentrate with fewexceptions on species with the SC(SiMe3)3 fragment. The majority of samples in this section,however, are based on M3 cluster compounds with a �3-C¼S ligand or similar clusters inwhich one or two Co atoms are replaced by other transition metals; addition of an electrophileat the C¼S sulfur atom gives a �3-methylidine ligand, which contributes three electrons to thecluster.
6.11.3.2.1 Compounds with the SCN3 core
A series of heterocyclic compounds with this core were prepared recently. The reaction ofN-[(trimethylsilyl)methyl]imminium triflate with various imines in the presence of CsF gave thecompounds 98 in 40% to 70% yields as depicted in Scheme 30. Similarly, the reaction of thetriflate with diethyl azodicarboxylate generated the compounds 99 in yields between 20% and74% <2001H243>.
A new series of transition metal complexes was prepared containing the tris(pyrazoly)methan-sulfonato ligand 100 (Tpms). Toward transition metals, Tpms can act as a bidentate or, tridentateligand. This new ligand was prepared as the Tl salt by adding excess of Tl2CO3 to an aqueoussolution of LiTpms. Recrystallization from methanol gave 60% yield <2000AG2464,2001EJIC1415>. The complex 101 was obtained from the reaction of TlTpms with[Rh(CO)2Cl]2 under 2–3 atm CO in THF is quantitative yield; without a positive CO pressure,
342 Functions Containing Two or One Chalcogens (and No Halogens)
the dinuclear complex 102 was formed quantitatively. If the reaction was carried out with[Rh(cod)Cl]2 in CH2Cl2, the complex 103 (dien=cod) was obtained. Similarly, the reaction ofTlTpms with [Rh(nbd)Cl]2 in dichloromethane generated the complex 104 (dien=nbd). Additionof PPh3, PMe3, or PCy3 to 101 produced the complexes 105a–105c (PR3=PPh3, PMe3, PCy3).With potassium diphenyl(sulfonatophenyl)phosphane 106 was obtained in 40% yield. Most of thecomplexes have been characterized by X-ray analyses <2001EJIC1415>. The complex 105(R=PMe3) activated benzene upon irradiation to form 107, which was carbonylated with CO togive 108; the reactions are collected in Scheme 31 <2001EJIC3113>. Treatment of CuCl in EtOH/MeCN with LiTpms and PPh2C6H4COOH-4 produced the complex 109 in 76% yield<2003JIB(94)348>.
NN
SO3
NN S
N
N
N
=
–
S
N
N
N Rh CO
CO
S
N
N
N Rh
OC
COCO
Rh N
N
N
S
N
N
N Rh
S
N
N
N Rh(dien)S
N
N
N Rh PR3
CO
PR3
K[PPh2PhSO3]
S
N
N
N Rh PPh2PhSO3
CO
_
N
N
PMe3
Ph
H
SN
N
N RhPMe3
COPh
H
COC6H6
100 = Tpms
101
102
103
104
105106
107 108
S
Scheme 31
N
HN SMe
NHPh
TsAr
N N
HN SMe
NHPh
EE
EN N
E
ArHC N
Ts
Me3SiN
PhHNSMe
98
99
Ar = Ph, p -ClC6H4, p -NO2C6H4E = COOEt
Scheme 30
Functions Containing Two or One Chalcogens (and No Halogens) 343
N N
S
NN
NN
S
NN
111
SNN
N CuPPh2
PPh2
COOH
COOH
109
The compounds 110 in Scheme 32 contain the MFe3S4 cluster and are obtained as the[Me4N]2[VFe3S4R4] salts. The chloro derivative 110 (R=Cl) was obtained in 38% yield fromthe DMF complex by reacting with LiTpms in acetonitrile followed by addition of Me4NCl.Further reaction with NaSR compounds generates 110 (R=SEt) and 110 (R=S-Tol-p) in 48%yield; similarly, the action of NaO-Tol-p produces the complex 110 (R=O-tol-p) <2002IC958>.
The formation of the compound 111 was mentioned in <2001AG1247>.
6.11.3.2.2 Compounds with the SCNSi2 core
The reaction of BtCHSMe(SiMe3) with BuLi followed by subsequent addition of Me3SiClafforded the compound 112 according to Scheme 33 <2000JOC9206>.
110
100
NN
SO3
NN S
N
N
N
=
–
N
N
S
V
Fe
Fe
SS
S
Fe
R
R
R
N
NN
S
S
V
Fe
Fe
SS
S
Fe
R
R
R
DMF
DMFDMF
Scheme 32
NN
N
SMeMe3Si
NN
N
SMe
SiMe3
Me3Si
BuLi, Me3SiCl
112
Scheme 33
344 Functions Containing Two or One Chalcogens (and No Halogens)
6.11.3.2.3 Compounds with the SCPFe2 core
The cationic complex [Cp2Fe2(CO)2(�-CSMe)]+ was allowed to react with ButP(H)SiMe3/DBU inMeCN to give the unstable complex 113, which loses CO to produce finally black 114 in 36% yield,which was characterized by an X-ray analysis as depicted in Scheme 34 <1997ZN(B)655>.
6.11.3.2.4 Compounds with the SCPNi2 core
The dinuclear nickel complex 115 was prepared in 36% yield from the reaction of [Ni(cod)(PMe3)2]with thiophosgene in toluene at �78 �C and characterized by an X-ray analysis <1998AG2385>.
Ni Ni
SPMe3
PMe3
ClMe3P
Cl
115
6.11.3.2.5 Compounds with the SCPMnRe core
The complexes with the SCPMnR core were prepared according to Scheme 35. Thus,Na2[MnRe(CO)6(S2CPR3)] (R=Pri, Cy) reacts with MeI in THF to give 116 and with Pt(cod)Cl2to produce 117 with a dimetallacyclopentadienyl ring in 53% yield. Addition of PEt3 to 116generates the complex 118 in 82% yield <2002AG3034>.
Cp(OC)Fe Fe(CO)Cp
SPHBut
CO
Me
CpFe Fe(CO)Cp
SPHBut
CO
Me
–CO
113 114
Scheme 34
[MnRe(CO)6(S2CPR3)]2–
(OC)3Re Mn(CO)3
SPR3
S
Et3P(OC)2Re Mn(CO)3
SPR3
CO
S
Mn(CO)3
(cod)Pt Re(CO)3S
PR3
116
118
117
a, R = Pri,
b, R = Cy
Scheme 35
Functions Containing Two or One Chalcogens (and No Halogens) 345
6.11.3.2.6 Compounds with the SCSi3 core
New compounds with this core are collected in Schemes 36 and 37. The Si-methylatedhexasilabicyclo[2,2,2]octane 119 was prepared in 62% yield from the monolithio derivative(obtained from the H derivative and the superbase BuLi/ButOK) and (PhS)2 in THF at �42 �C(Scheme 36) <2000JOM(611)12>. (Me3Si)3CSO2Li 120 was obtained from the reaction between(Me3Si)3CLi (from (Me3Si)3CH and MeLi in ether/THF) and SO2 at �78 �C; addition of Cl2 at thistemperature yields (Me3Si)3CSO2Cl 121 in 71% yield (m.p. 131 �C) <2000CJC1642>.
Me3Si
LiO2S SiMe3
SiMe3
120
Me3Si
ClO2S SiMe3
SiMe3
121
The starting compound for a series of complexes is LiSC(SiMe3)3 (see chapter 6.11.3.2.2 inCOFGT (1995)), which exists in a tetrameric form in hexane consisting of an Li4S4 cubaneskeleton. A further complex was obtained by the reaction with YbCl3 in the presence ofTMEDA generating [Li(TMEDA)][YbCl3{SC(SiMe3)3(TMEDA)}] 122; both compounds werecharacterized by an X-ray analysis and the anion is shown in Scheme 37 <1995KID(26)242>.
6.11.3.2.7 Compounds with the SCSi2P core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.2.3).
6.11.3.2.8 Compounds with the SCPSiLi core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.2.4).
Li
S
S
S
LiLi
Li
S
S = SC(SiMe3)3
NMe2
Yb
Me2N Cl
Cl
S
SiMe3
SiMe3
SiMe3
Cl
YbCl3
TMEDA
122
Scheme 37
Si
Si
Si
Si
Si
Si
Si = SiMe3
HSi
Si
Si
Si
Si
SiPhS
BuLi, (PhS)2
119
Scheme 36
346 Functions Containing Two or One Chalcogens (and No Halogens)
6.11.3.2.9 Compounds with the SCSi2Li core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.2.5).
6.11.3.2.10 Compounds with the SCN2Fe core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.2.6).
6.11.3.2.11 Compounds with the SCNSnPt core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.2.7).
6.11.3.2.12 Compounds with the SCSiSnLi core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.2.8).
6.11.3.2.13 Compounds with the SCFe3 core
The reaction of the in situ generated radical complex [Fe2(�-CSR)(�-CO)(CO)2Cp2] with[Fe2(CO)4Cp2] under UV photolysis leads to the novel �3-carbyne complex 123 (a, R=Me;b, R=Et) in 30% yield; the methyl derivative was characterized by an X-ray analysis. Alkylationof this complex with MeSO3CF3 afforded the cationic complex 124, as shown in Scheme 38; allCO groups are bridging ones <1993G703>.
6.11.3.2.14 Compounds with the SCRu3 core
The cluster 125 was obtained in 63% yield by stirring a solution of the complex[Ru3(CO)4(�-PCy2)(�-dppm)] in CS2 for 2 days. The cluster was characterized by an X-rayanalysis <2002ZAAC2247>.
(OC)CpFeFeCp(CO)
FeCp(CO)
S
R
(OC)CpFeFeCp(CO)
FeCp(CO)
S
MeMe
+MeSO3CF3
123 124
Scheme 38
Functions Containing Two or One Chalcogens (and No Halogens) 347
(OC)3OsOs(CO)3
Os(CO)3
S
X
H
H
126
Cy2P
RuRu
Ru
S
S
S
S
PPh2
PPh2
Cy2P
125
6.11.3.2.15 Compounds with the SCOs3 core
The neutral clusters 126 (X=CH2, S) were synthesized in 50% yield by the reaction of thecorresponding Cl-cluster Os3H3(CO)9CCl with 1 equiv. of DBU and a 10-fold excess of thiane or1,4-dithiane <1995JCS(D)2735>.
6.11.3.2.16 Compounds with the SCCo3 core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.2.10).
6.11.3.2.17 Compounds with the SCAu3 core
The only known complex with the SCAu3 core was obtained by the reaction of [Au(acac)PPh3]with [Me3SO]ClO4, which generated the trinuclear cationic Au complex 127 <1996JA699>.
Ph3PAuAuPPh3
AuPPh3
S
O
+
127
6.11.3.2.18 Compounds with the SCFe2Co core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.2.11).
6.11.3.2.19 Compounds with the SCFeCo2 core
A series of cationic compounds (128a–128h) was prepared in 70% to 80% yields by alkylationof the corresponding �3-CS complex (L=PPh3, P(OMe)3, or P(OPh)3) with the appropriate RXsalt (Scheme 39, Table 5); the crystal structure of 128a is reported <1998JOM(551)139>. Thecomplex 129 was obtained according to Scheme 40 in 75% yield in refluxing CS2 (12 h)<1998CC1577>.
348 Functions Containing Two or One Chalcogens (and No Halogens)
6.11.3.2.20 Compounds with the SCCo2W core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.2.12).
6.11.3.3 Methanes Bearing One Selenium or One Tellurium Function and Three Functions Derivedfrom the Group V (15) Element, Metalloid, and/or a Metal
The compounds bearing the SeC or TeC unit, with few exceptions, are restricted to examples with theSiMe3 group and the resulting trimethylsilylmethyl group (Me3Si)3C is generally abbreviated as TSi.
6.11.3.3.1 Compounds with the SeCN3 core
No further advances have occurred in this area since the publication of COFGT (1995) (chapter6.11.3.3.1).
S
CpCoFe
CoCp
S
CO
CO
S
CpCoFe
CoCp
SR
CO
CO
L
RX
+
X–
128a–h
L
Scheme 39
Table 5 R, L, and X for the compounds 128a–128h
Nr 128 L R X
a PPh3 Me SO3CF3
b PPh3 Et Ic PPh3 Allyl Id PPh3 HgCl HgCle P(OPh)3 Me BPh4f P(OPh)3 Et BPh4g P(OMe)3 Me BPh4h P(OMe)3 Et BPh4
S
CpCoFe
CoCp
S
CO
CO
S
CpCoFe
CoCp
S
S
S
CO
PPh3 PPh3
CS2
129
Scheme 40
Functions Containing Two or One Chalcogens (and No Halogens) 349
6.11.3.3.2 Compounds with the SeCSi3 core
This section contains compounds of the general type (Me3Si)3CSeX(TsiX) in which the Se atom isfurther bonded to other groups including transition metals.
Reaction of TsiSeI with the corresponding thiocarbonyl derivatives (a, R=Me; b, R=Prn) intoluene forms the compounds 130 in 85% yield, as shown in Scheme 41 <2001AG2486>. If thecompound TsiSeLi(DME) was treated with InCl3 in hexane, the compound (TsiSe)3In wasformed in 31% yield and characterized by an X-ray analysis <1995IC4854>. Treatment ofTsiSeLi(DME) with CuCl (in DME solution) or Cu(PCy3)2BF4 (in ether) leads to the complexesCuSeTsi (31% yield) and Cu(PCy3)SeTsi (35% yield), respectively; Cu(PCy3)SeTsi is dimericwith an SeCuSeCu four-membered ring and characterized by an X-ray analysis. The similarreaction with AgNO3 or AgBr(PCy3)2 produced the complexes AgSeTsi (56% yield) and Ag(PCy3)-SeTsi (30% yield), respectively. The first one is tetrameric with an AgSeAgSeAgSeAgSe eight-membered ring and also characterized by an X-ray analysis. If the reaction with CuCl was carriedout in benzene, the salt [Li(DME)2]{Cu[SeTsi]2} was obtained in 23% yield <1994IC1797>.
6.11.3.3.3 Compounds with the TeCSi3 core
Most of the compounds that have been described with the SeCSi3 core are also known with theTeCSi3 core and similarly to the selenium derivatives, only compounds with the SiMe3 group areknown. Thus, compounds of the general type (Me3Si)3CTeX in which the Te atom is furtherbonded to other groups including transition metals have been prepared by the same workinggroups as reported for the corresponding selenium compounds. The (Me3Si)3C group is abbre-viated as Tsi.
A solution of (THF)LiTeC(SiMe3)3 in toluene was added to a solution of Cu(PCy3)BF4 toproduce the complex Cu(TeTsi)PCy3 in 51% yield; see also compounds with the SeCSi3 core<1994IC1797>.
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352 Functions Containing Two or One Chalcogens (and No Halogens)
Biographical sketch
Wolfgang Petz was born in Munich. He stu-died at the University of Munich, where heobtained his diploma in 1966 and his Ph.D. atthe University of Marburg in 1969 under thedirection of Professor Heinrich Noth. After 2years as scientific assistant he was appointedto Dozent auf Zeit at the University of Mar-burg, where he finished his Habilitation in1979. In 1982 he moved to the Gmelin Institutof the Max-Planck-Society where he wasauthor and editor of many organometallicvolumes and in 1990 he became chief editorof the organometallic division. After closureof the Gmelin Institut in 1998 he moved to theMPI for Bioinorganic Chemistry in Mulheimand took up his present position as apl. Pro-fessor at the University of Marburg. Hisscientific interests are on the field of organo-metallic chemistry, in particular carbene,difluorocarbene, and thiocarbonyl compoundsincluding carbanion chemistry of transitionmetal carbonyl compounds.
Frank Weller was born in Stuttgart, Germany.He studied at the local University and got hisDiploma in 1968. Having worked out a doc-toral thesis with Professor K. Dehnicke inMarburg, Germany by 1971, he stayed there,and did some work mainly in the fields ofvibrational spectroscopy and, later on, crystal-lography. Except for his early stage, when hewas dealing with methylmercuric species, hisscientific interests were, according to hismainly methodic activities, spread over awide range of fields.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 317–353
Functions Containing Two or One Chalcogens (and No Halogens) 353
6.12
Functions Containing
at Least One Group 15
Element (and No Halogen
or Chalcogen)
S. SABA and J. A. CIACCIO
Fordham University, New York, NY, USA
6.12.1 METHANES BEARING FOUR GROUP 15 ELEMENTS 3566.12.1.1 Four Similar Group 15 Element Functions 3566.12.1.1.1 Four nitrogen functions 3566.12.1.1.2 Four phosphorus functions 358
6.12.1.2 Three Similar and One Different Group 15 Element Functions 3596.12.1.2.1 Three arsenic functions 359
6.12.1.3 Two Similar and Two Different Group 15 Element Functions 3596.12.2 METHANES BEARING THREE GROUP 15 ELEMENTS
AND A METALLOID OR A METAL FUNCTION 3596.12.2.1 Three Similar Group 15 Elements 3596.12.2.1.1 Three nitrogen functions 3606.12.2.1.2 Three phosphorus functions 360
6.12.3 METHANES BEARING TWO GROUP 15 ELEMENTS AND METALLOIDAND/OR METAL FUNCTIONS 360
6.12.3.1 Two Similar Group 15 Elements 3606.12.3.1.1 Two nitrogen functions 3606.12.3.1.2 Two phosphorus functions 3616.12.3.1.3 One phosphorus, two silicon, and one arsenic functions 366
6.12.4 METHANES BEARING ONE GROUP 15 ELEMENT AND METALLOIDAND/OR METAL FUNCTIONS 367
6.12.4.1 Nitrogen Functions 3676.12.4.1.1 One nitrogen and three boron functions 3676.12.4.1.2 One nitrogen and three silicon functions 3676.12.4.1.3 One nitrogen, two silicon, and one metal functions 3696.12.4.1.4 One nitrogen and three metal functions 369
6.12.4.2 Phosphorus Functions 3726.12.4.2.1 One phosphorus and three metalloid functions 3726.12.4.2.2 One phosphorus and three metal functions 3746.12.4.2.3 One phosphorus, one silicon, and two metal functions 376
355
6.12.1 METHANES BEARING FOUR GROUP 15 ELEMENTS
6.12.1.1 Four Similar Group 15 Element Functions
6.12.1.1.1 Four nitrogen functions
Several reasonably general methods for the construction of molecules bearing this function havebeen previously described <1995COFGT(12)359>. These include (i) nucleophilic exchange ofchlorine atoms with amine functions, (ii) addition of amine functions to carbon–nitrogen doublebonds, (iii) addition of nitrogen-bearing carbons to nitrogen–nitrogen double bonds, and(iv) exchange of a nitrogen-bearing group with a nitrogen-bearing carbanion. A few cyclic andacyclic compounds featuring four nitrogen functions have been reported since 1995. These includestructures with two, three, or four similar nitrogen functions. While some of these compoundswere prepared by adaptation of previously developed methods, a few were generated bymiscellaneous syntheses. These preparations are described below.
(i) By nucleophilic exchange of chlorine atoms
(a) From tetraalkylchloroformamidinium chlorides. A few tetrakis(dialkylamino)methanes weresynthesized by adaptation of the method previously described for preparation of tetrakis(dimethyl-amino)methane from reaction of a tetraalkylchloroformadinium chloride with lithium dialkyl-amides (Equation (1) and Table 1); yields were low to moderate. Single-crystal structural studieson tetrakis(dimethylamino)methane and tetra(pyrrolidinyl)methane, as well as reactivity studieson hydrolysis of the former compound, have also been reported <1997CB(130)1739>.
R2N
R2NCl
+
Cl– R2NNR2
NR2
NR22 LiNR2 ð1Þ
(b) From pentacarbonyl(trichloromethylisocyanide)chromium(0). Reaction of pentacarbonyl(tri-chloromethylisocyanide)chromium(0) with imidazole afforded a 70% yield of the electron-deficientisocyanide complex pentacarbonyl[tris(imidazol-1-yl)methylisocyanide]chromium(0) (Equation (2))<1995JOM(489)27>.
C N CCl3(OC)5Cr + N N H C N(OC)5CrN
NN
N
N
N70%
CH2Cl2, rt, 6 hð2Þ
(ii) By nucleophilic addition to guanidinium salts
N,N,N0,N0,N00,N00-Hexamethylguanidinium chloride, when reacted with sodium hydride/dimethyl-amine in the presence of trimethyl borate, produced a mixture of tetrakis(dimethylamino)-methane and tri(dimethylamino)orthoformamide (Equation (3)). The reaction was conducted inanhydrous THF affording, after crystallization from acetonitrile, colorless crystals oftetrakis(dimethylamino)methane in 11% yield <2000JPR(342)256>.
Table 1 Nucleophilic exchange of chlorine and additionof dialkylamides
R Yield (%) References
Me 54 <1997CB(130)1739>Et 25 <1997CB(130)1739>�(CH2)4� 49 <1997CB(130)1739>�(CH2)5� 12 <1997CB(130)1739>
356 Functions Containing at Least One Group 15 Element
Me2NNMe2
Me2N
+
Cl–NaH, HNMe2, B(OMe)3
THF, 11%Me2N
NMe2
NMe2
NMe2 HNMe2
NMe2
NMe2+ ð3Þ
Similarly, as part of a general preparative scheme for selective N-monoalkylation and 1,4-N,N-dialkylation of 1,4,7,10-tetraazacyclododecane, 1, octahydro-2a,4a,6a,8a-tetraazapenta-leno[1,6-cd]pentalene, 3, was obtained in higher than 95% yield from guanidinium chloride 2upon reaction with 1M NaOH at 20 �C (Scheme 1). The reagents and reaction conditions forconversion of 3 to its N-monoalkyl and 1,4-N,N-dialkyl derivatives were also reported<1998ACS1247>.
(iii) Miscellaneous syntheses
A few isolated reactions leading to methanes bearing four nitrogen functions have also appearedin the literature since 1995.
(a) The high activation of the C�F bond in the anions of salts 4 and 5 was utilized in theinteraction of these salts with silylated azoles. Tetrapyrrolemethane was prepared in 90% yield bytreatment of salts 4 and 5 with trimethylsilylpyrrole. Salt 4 reacted readily at �10 �C while salt 5required 24 h at room temperature (Equations (4) and (5)) <2001AG(E)1247>.
[CF3S(NMe2)2]+ [CF3S]– TMSN+ N C4
4
4 3TMSF + . . .+ ð4Þ
[(Me2N)2CC(NMe2)2]2+ [CF3S–]2 TMSN8+ N C4
+ 6TMSF + . . .2
5
ð5Þ
(b) An NMR and GC-MS study of thermolysis fragments from the 1:1 adduct obtained byreaction of diisopropylcyanamide and trifluoroacetic anhydride led to detection of a compoundwith mass 431. The structure suggested for this compound was that for 4-(diisopropylamino)-4-(trifluoroacetoxy)-2,6-bis(trifluoromethyl)-4H-1,3,5-oxadiazine, 6. Another compound pro-duced from reaction of compound 6 and N,N-diisopropyl-N0,N0-bis(trifluoroacetyl)urea, 7, hada mass of 418 and was characterized as 4,4-bis(diisopropylamino)-2,6-bis(trifluoromethyl)-4H-1,3,5-oxadiazine, 8 (Equation (6)). The former compound is the principal component in theoriginal adduct <1997JOC9070>; however, the expected by-product shown in Equation (6) wasnever detected.
O
NN(Pri)2N OCOCF3
CF3F3C(Pri)2N C
ON(COCF3)2
O
NN(Pri)2N N(Pri)2
CF3F3C
OC OF3C C
ON(COCF3)2+
6 7 8
+ ð6Þ
(c) Tetrapyrazolylmethane (Cpz4) was used for the synthesis of the binuclear adduct[{CpMo(CO)2}(�-Cpz4){Re(Cl)O3}][BF4] (81% yield) formed between the high oxidation staterhenium complex ClReO3 and a molybdenum-based organometallic ligand bearing a bridge withnitrogen donors like Cpz4 <1998POL1091>.
NH HN
NH HN
i. 37% HCl
ii. C(OEt)4EtOH, 78 °C, 19 h
EtOH, 20 °C 1M NaOH
20 °C, 1 h
N N
N N
1 2 3
Cl–NH N
N N
+
Scheme 1
Functions Containing at Least One Group 15 Element 357
(d) In a study of some properties of N-polynitromethyl derivatives of fused benzotriazoles, 2,6-bis(trinitromethyl)benzo[1,2-d;4,5-d0]ditriazole-4,8-dione, 11, was prepared by nitration of2,6-bis(dinitromethyl)benzo[1,2-d;4,5-d0]ditriazole-4,8-dione, 9, and its sodium or potassiumsalts, 10, with conc. HNO3 (Scheme 2). Treatment of 11 with hydroxylamine afforded a chemi-cally unstable dioxime that gradually decomposed to 11 <1993IZV1623>.
(e) Nucleophilic displacement of a nitro group with an azido group was shown to occur inpolynitromethanes. It was found that reaction of tetranitromethane with NaN3 in DMSO-CH2Cl2afforded azidotrinitromethane in 20–24% yield (Equation (7)). When this reaction was carried outin pure DMSO or DMF, the yields were 10–14%. In aqueous acetone, this reaction produced amixture of azidotrinitromethane and diazidodinitromethane (identified by GLC) that were diffi-cult to separate. Pure diazidodinitromethane was obtained in 12% yield by the reaction ofteranitromethane with excess NaN3 in aqueous ethanol at 5–10 �C. Diazidodinitromethane wasalso detected by GLC in the reaction of the monoazide with NaN3 in aqueous ethanol<1997IZV338>.
C(NO2)4NaN3
C(NO2)3N320–24%
ð7Þ
(f) In the course of syntheses of condensed pyrazolo derivatives, reaction of 5-amino-3-aryl-amino-1H-pyrazole-4-carbonitrile, 12, with dicyandiamide in refluxing ethanol afforded com-pounds for which Structure 13 was suggested (Equation (8)) <1997CCA1039>. Thesestructures were based on spectral and elemental analyses of the products; however, only MSdata for compound 13 (Ar=C6H4�CH3�m) were reported.
NNH
NC NH2
ArHN+ NC N
NH2
NH2
EtOH, 78 °C, 4 h
65–70% NN
NC NH2
ArHN
NH2
NH2
NHCN
12 13Ar = C6H4-CH3-mAr = C6H4-F-p
ð8Þ
6.12.1.1.2 Four phosphorus functions
Only two reports describing the preparation of compounds of this class have appeared in theliterature since 1995. Treatment of bis(trimethylsilyl)methylidene triphenylphosphorane, 14, witha phosphorus trihalide gave the corresponding dihalophosphanyl ylides, 15, which self-condensedin pyridine (X=Cl) or a mixture of benzene and pyridine (X=Br) to selectively afford tetramershaving cations with a tetraphosphabicyclo[2.2.2]octane (1,3,5,7-tetraphosphabarrelane) structure,16 (Scheme 3) <1995AG(E)1853>. The chloride salt was formed as a complex with pyridine in43% yield; no yield was reported for the bromide salt. Reaction of the tetraphosphabarrelanechloride with either aluminum trichloride or gallium trichloride converted the singly charged
NN
NNN
N
O
O
CH(NO2)2(NO2)2HCHNO3
NN
NNN
N
O
O
C(NO2)3(NO2)3C60 °C, 24 h
44%
NN
NNN
N
O
O
CM(NO2)2(NO2)2MC
HNO3
MOAc 119
10
M = Na+, K+
Scheme 2
358 Functions Containing at Least One Group 15 Element
cation to a tetracation having a cubane structure (17; 20% yield for M=Al, and 50% yield forM=Ga), whereas treatment with antimony pentachloride afforded a mixture of dications, onewith the barrelane structure preserved, 18, and a minor amount of a dication with a tetra-phosphabicyclo[3.3.0]octane structure <1998ZN(B)1285>.
6.12.1.2 Three Similar and One Different Group 15 Element Functions
6.12.1.2.1 Three arsenic functions
In a reaction analogous to the synthesis of a 1,3,5,7-tetraphosphabarrelane cation described inSection 6.12.1.1.2, treatment of 14 with arsenic trichloride afforded a 1,3,5,7-tetraarsabarrelanecation, 20, along with minor amounts of 1,3-diarsetane and 1,3,5-triarsinane cations (Scheme 4)<2000CEJ3531>. The reaction proceeded via the intermediacy of a dichloroarsanyl trimethylsilylylide, 19 that tetramerized to 20 over a period of weeks. X-ray analysis of the crystalline cation 20disclosed average As�Cl bond lengths of 249 pm, reported to be by far the longest to be observedat a three-coordinate, pyramidal arsenic atom.
6.12.1.3 Two Similar and Two Different Group 15 Element Functions
No further advances have occurred in this area since the publication of chapter 6.12.1.3 in<1995COFGT(12)359>.
6.12.2 METHANES BEARING THREE GROUP 15 ELEMENTSAND A METALLOID OR A METAL FUNCTION
6.12.2.1 Three Similar Group 15 Elements
Two reports have appeared in the literature since 1995 featuring compounds of this class; eachdescribing structures containing a carbon that bears one metal function and either three nitrogenor three phosphorus functions.
Ph3P C(TMS)2 Ph3PTMS
PX2
PX3
P
PP
P
PPh3
PPh3
Ph3P
Ph3P
X X
X
X–
(–TMSX)
P
PP
P
PPh3
PPh3
Ph3P
Ph3P
Cl Cl
Cl
SbCl52–
Cl
P
PP P
PPh3
PPh3Ph3PPPh3
SbCl5
X = Cl
X = Cl, Br1415
16
17
18
(MCl4–)4
MCl3
CH2Cl2
Scheme 3
Ph3PTMS
AsCl2
AsCl3, Pyr
As
AsAs
As
PPh3
PPh3
Ph3P
Ph3P
Cl Cl
Cl
AsCl4–
(–TMSCl )
1920
62%Ph3P C(TMS)2
14
Scheme 4
Functions Containing at Least One Group 15 Element 359
6.12.2.1.1 Three nitrogen functions
In the course of studies on preparation of anionic tris(3,5-dimethylpyrazolyl)-containing ligandsin transition metal chemistry, it was stated that deprotonation of HC(Me2Pz)3 (Pz=pyrazolyl)occurred cleanly without prior complexation to a metal center by reaction with MeLi in THF toform LiC(Me2Pz)3 in quantitative yield. The use of this compound as a reagent was establishedtoward the preparation of a titanium-containing zwitterionic complex displaying a nakedsp3-hybridized carbanion <2001CC705>.
6.12.2.1.2 Three phosphorus functions
Treatment of tris(diphenylphosphanyl)methane, 21, with an acetylacetonato (acac) gold(I) com-plex, 22, led to the formation of a neutral gold(I) complex, 23, with the gold atom linearly boundto both triphenylphosphine and the carbon of the methanide ligand, an unprecedented coordina-tion type for tris(phosphanoyl)methanide and its derivatives (Equation (9)) <1996CB585>.
Ph3P AuPPh2O
PPh2OPPh2O
CH[PPh2(O)]3 + Au(acac)PPh3 + acacH
22 232179%
ð9Þ
6.12.3 METHANES BEARING TWO GROUP 15 ELEMENTS AND METALLOIDAND/OR METAL FUNCTIONS
6.12.3.1 Two Similar Group 15 Elements
6.12.3.1.1 Two nitrogen functions
Only two compounds featuring a carbon attached to two nitrogen functions and two metalfunctions have been described since 1995. Both compounds exhibit carbene metal interactionsand the nitrogens are part of five-membered heterocycles.
Deprotonation of 3-borane-1,4,5-trimethylimidazole, 24, with BunLi afforded lithium 3-borane-1,4,5-trimethylimidazol-2-ylidene, 25 (Equation (10)). An X-ray diffraction study on a singlecrystal of this salt grown from a THP solution at 4 �C revealed dimeric units of two carbeneanions connected by two lithium cations. The nitrogen-flanked carbene carbons have a shorter(2.169 A) and a longer (2.339 A) contact with the lithium cations <1998EJI843>.
N
NMe
MeMe
BH3
BunLi
THF-hexane, –40 °C N
NMe
MeMe
BH3
Li+
-+
-
24 25
ð10Þ
The reaction of 2,6-bis(imidazolmethyl)pyridine, 26, and 1-methyl-2,5-bis(trimethylamino-methyl)pyrrole diiodide, 27, in nitromethane produced the cyclophane diiodide 28 (Equation(11)). Treatment of an aqueous solution of 28 with NH4PF6 afforded the dihexafluorophosphatesalt which, upon deprotonation with Ag2O in DMSO at 55 �C, afforded a dimeric silverN-heterocyclic carbene complex with composition [Ag4(28*)2][PF6]4, where 28* represents thedeprotonated 28. Both the 13C NMR and X-ray diffraction data on the carbene complex indicatedthat each carbene is interacting with two different silver atoms via �-bonding and �-bondinginteractions <2001CC1780>.
360 Functions Containing at Least One Group 15 Element
N
N
N N
N
+ NMe
Me3N
Me3N
2I–
+
+
N
N
N N
N
NMe
+
+ 2I–
MeNO2
26 27 28
N
N
N N
N
NMe
28*
ð11Þ
6.12.3.1.2 Two phosphorus functions
(i) Two phosphorus and two silicon functions
Only three practical syntheses of compounds of this class, all leading to the formation of diphos-phirane functionality, have been reported since 1995. The first involved protonation of the lithiumsalt of a persilylated 2,3,4-triphosphapentadienide, 29, the first of its kind reported, leading to abicyclic diphosphirane, 31 (no yield reported). The latter most likely arose from a valenceisomerization of intermediate 30 (Scheme 5) <1996AG(E)313>.
The same research group subsequently reported a reaction between dilithioferrocenylphospha-nide and dichlorobis(trimethylsilanyl)methane, leading to a mixture of a diferrocenyldiphosphirane,34 (65% yield), and a minor amount of a bis(methylene)phosphorane, 35. The authors explained theformation of these products by assuming an initial lithium–halogen exchange, affording a phos-phenoid and carbenoid that immediately dimerized with elimination of LiCl; further reaction of thedimer with either the phosphenoid or carbenoid led to 34 and 35, respectively. The predominance ofthe diphosphorane suggests an increased stability of the phosphenoid compared to the carbenoidunder these conditions (Scheme 6) <1997JOM(541)237>.
The third report described a reaction between a 1,2-dihydro-1,2-phosphasilete, 36, and [bis(tri-methylsilyl)methylene]chlorophosphane that led to a phosphaalkene-substituted phosphasilete, 37,in 93% yield, which then underwent a thermal isomerization to afford bicyclic diphosphirane 38 in80% yield (Scheme 7) <1999CEJ1581>.
PTMS
TMSCl
–LiCl –P(TMS)3
TMS PP
P TMSTMS
TMSHH+
P P
P
TMS
TMSTMS
TMS
H
P TMS
TMS
TMSP TMS P
PP TMS
TMS TMSLi+(DME)3
Li+(DME)3
29
3031
58%76%+ 2 LiP(TMS)2(THF)x
Scheme 5
Functions Containing at Least One Group 15 Element 361
(ii) Two phosphorus and two metal functions
A number of compounds of this class have been reported since 1995, the majority bearing twogold functions, in addition to a few compounds bearing two aluminum, chromium, lead, tin, ornickel functions.
(a) Two phosphorus and two gold functions. All but one of the recently reported syntheses ofcompounds bearing two phosphorus and two gold functions involved carbon metallation by theuse of basic acetylacetonato (acac) gold complexes, hydroxide, or hydride for deprotonation of amethylene or methine group bearing two phosphorus functions.
The reaction of trinuclear gold complex 39 with a fourfold excess of [Au(acac)PPh3] gaveheptanuclear gold complex 40 in which bis(diphenylphosphino)methanediide [bis(dppm)] bonds tofour gold atoms as an eight-electron donor ligand (Equation (12)) <1995OM2918>.
AuPPh2Ph2P
(C6F5)3Au
Ph2P PPh2
Au(C6F5)3 AuPPh2Ph2P
(C6F5)3Au
Ph2P PPh2
Au(C6F5)3
AuPPh3
AuPPh3
Ph3PAu
Ph3PAu
ClO4
ClO4
4 [Au(acac)PPh3]
39 40
CH2Cl2, 48 h, 80%
ð12Þ
In a similar fashion, a cyclic, linearly coordinated tetranuclear gold complex 41 with tridentatebis(dppm) ligands was treated with 2 equiv. of [Au(PPh3)2]ClO4, leading to deprotonation of theCH groups and the formation of the hexanuclear complex 42 in 75% yield (Equation (13))<1995CB121>.
Au AuPPh2Ph2P
Ph2P PPh2
H(acac)Au
H Au(acac)
Au AuPPh2Ph2P
Ph2P PPh2
AuPPh3Ph3PAu
Ph3PAu AuPPh3
(ClO4)22 [Au(PPh3)2]ClO4, 8 h
–2 acacH, 75%
41 42
ð13Þ
PLi2 PClLi
P
TMS
TMS PC(TMS)2
C(TMS)2
P
TMS
TMS
P
FeCl TMS
Cl TMS
FeFe
Fe
Fe
Li TMS
Cl TMS
Fe
+0 °C, ether
+
–2 LiCl +
32 33
32, –LiCl
33, –LiCl
65%34 35
Scheme 6
SiP
But
Ph
TMS
TMSTMS
ClPTMS
TMS SiP
But
Ph
P
TMSTMS
TMS
TMS
SiP
P
TMS
TMS
PhTMS TMS
But
+–TMSCl 180 °C, 2 h
93% 80%
36 37 38
Scheme 7
362 Functions Containing at Least One Group 15 Element
With the aim of developing controlled syntheses of heterometallic species of high nuclearity,Ruiz and co-workers <1997OM3388> investigated the chemistry of bis(dppm) derivatives ofruthenium and manganese. Treatment of the bis(dppm) derivative 43 (M=Mn, L=CO) withone molar equivalent of [AuCl(PPh3)] and excess KOH gave a mixture of dinuclear and tri-nuclear, 44, complexes in a 6:4 molar ratio; however, the trinuclear, 44 (90% yield), tetranuclear,45 (83% yield), and pentanuclear, 46 (81% yield), complexes were selectively obtained in thepresence of excess KOH by treatment of the same bis(dppm) derivative with two, three, and fourmolar equivalents of [AuCl(PPh3)], respectively. By contrast, partial metallation of the bis(dppm)derivative, 43 (M=Ru and L=CNBut or CNPh), was not possible, and only the correspondingpentanuclear complex, 46, could be isolated in pure form (L=CNBut, 78% yield; L=CNPh,81% yield) (Scheme 8 and Table 2).
Treatment of bis(pentafluorophenyl)gold(III) methanide complex 47 (Scheme 9) and tris(penta-fluorophenyl)gold(III) methanide complex 50 (Equation (14)) with [Au(acac)L] afforded the corre-sponding disubstituted products (80% [L=PPh3] and 74% [L=AsPh3] for the metallacycle 47; 71%[L=PPh3] for the acyclic compound). When complex 47 was treated sequentially with NaH and[Au(acac)PPh3] a four-membered methanide complex was afforded in 53% yield (Scheme 9)<1998POL2029>.
ML
L
Ph2P
Ph2PPPh2
PPh2
ML
L
Ph2P
Ph2PPPh2
PPh2
AuPPh3
AuPPh3
Ph3PAuPh3PAu
4 [AuClPPh3]
KOH, CH2Cl2
ML
L
Ph2P
Ph2PPPh2
PPh2
Ph3PAuH H
AuPPh3
ML
L
Ph2P
Ph2PPPh2
PPh2
AuPPh3
AuPPh3
Ph3PAuH
[AuClPPh3]2 [AuClPPh3]
KOH, CH2Cl2 KOH, CH2Cl2
[AuClPPh3]
KOH, CH2Cl2
43
44
45
46
n
n
n
Scheme 8
Table 2 Controlled syntheses of heterometallic species of high nuclearity
Compound M L n Yield (%) References
44 Mn CO 1+ 90 <1997OM3388>45 Mn CO 1+ 83 <1997OM3388>46 Mn CO 1+ 81 <1997OM3388>46 Ru CNBut 2+ 78 <1997OM3388>46 Ru CNPh 2+ 81 <1997OM3388>
S PPh2
PPh2SAu
C6F5
C6F5
ClO4
S PPh2
PPh2S
AuC6F5
C6F5
ClO4
AuLAuLAu PPh2
SC6F5
C6F5
Ph3PAu PPh2
S
2 [Au(acac)L]
CH2Cl2, 2 h
i. NaHii. [Au(acac)PPh3]
48 47 49
53%
Scheme 9
Functions Containing at Least One Group 15 Element 363
SPh2P
PPh2S(C6F5)3Au
SPh2P
PPh2S(C6F5)3Au
AuPPh3
AuPPh32 [Au(acac)]PPh3, CH2Cl2, 1 h
71%
50
ð14Þ
In a report on the synthesis of a family of cyclic palladium complexes containing N,P-diphos-phinomonoimine ligands, exposure to two molar equivalents of [Au(acac)PPh3] led to doubledeprotonation and functionalization of a palladium complex having an acidic methylene group(Equation (15)) <1998OM4544>.
PdPPh2
Ph2P
N
N
N
Tol
Tol
2 [Au(acac)PPh3], CH2Cl2, 36 h
88%Pd
PPh2
Ph2P
N
N
N
Tol
Tol
AuPPh3Ph3PAu
OTf OTf
ð15Þ
In another report detailing a synthesis of this class of compound by deprotonation and metalla-tion of an acidic methylene or methine, gold ferrocenyl methanide derivative 52 was prepared in86% yield when 51 was treated with [O(AuPPh3)3]ClO4 (Equation (16)) <1999ICA60>.
PPh2
PPh2 PPh2
PPh2
Ph3PAu AuPPh3
AuPPh3
Fe
ClO4
Fe
(ClO4)2
86%
5251
[O(AuPPh3)3]ClO4, CH2Cl2, 2 h ð16Þ
Finally, a dinuclear complex 53 with a carbon bearing two gold functions and two phosphorusfunctions was prepared in 70% yield from the reaction of the diylide C(PPh3)2 with AuCl-tetrahydrothiophene (tht) complex in a 1:2 molar ratio (Equation (17)) <2002OM5887>.
2 AuCl(tht) AuAu PPh3
PPh3
Cl
Cl53
C(PPh3)2, THF, 1 h
70%ð17Þ
(b) Two phosphorus and two aluminum functions. Since the mid-1990s, a notable amount ofinterest has focused on the development of nitrogen donor complexes as alternatives to cyclopenta-dienyl groups on metals, with impact on homogeneous catalysis. One study investigating bis(imino-phosphorano)methane chemistry led to the synthesis of novel aluminum complex 55 (67% yield) byboth single and double, stepwise deprotonation of the ligand’s methylene backbone (Scheme 10)<1999OM4241>. A patent also appeared that describes the preparation of derivatives of the alumi-num complex with various groups attached to nitrogen, phosphorus, and aluminum, and it outlinesprocesses for polymerizing various alkenes using the various complexes <1999USP6235919B1>.
Ph2P
Ph2P N
NTMS
TMS
Ph2P
Ph2P N
NAl
MeMe
TMS
TMS
PPh2
Me2Al
Ph2P
AlMe2
N NTMS TMSAlMe3, PhMe, 20 °C AlMe3, PhMe, 120 °C
2 AlMe3, PhMe, 120 °C
68%
67%
5554
Scheme 10
364 Functions Containing at Least One Group 15 Element
(c) Two phosphorus and two tin, lead, or chromium functions. Disilylated bis(iminophosphor-ano)methane, 54, was reported to lead to 1,3-dimetallacyclobutanes (56–58) upon monodeproto-nation with BunLi and treatment with PbCl2 <2001AG(E)2501> (Equation (18)), doubledeprotonation with BunLi and treatment with CrCl2(THF)2 (Equation (19)) <1999CC1993>,and direct treatment with M[N(TMS)2]2 (M=Sn, 70% yield; Pb, 80% yield, Equation (20)),<2001AG(E)2501>.
Ph2P
Ph2P N
NTMS
TMS
LiBunLi, THF PbCl2, Et2O,18 h Pb
Pb
PPh2
PPh2
N
N
Ph2P
Ph2P N
N
TMS TMS
TMSTMS
84%
56
Ph2P
Ph2P N
NTMS
TMS54
ð18Þ
Ph2P
Ph2P N
NTMS
TMS
2 BunLi, THF LiLi Cr Cr
Ph2P
Ph2P
PPh2
PPh2
N
NN
NTMS
TMSTMS
TMS
CrCl2(THF)2, THF, 2 days
56%
57
Ph2P
Ph2P N
NTMS
TMS54
ð19Þ
M[N(TMS)2]2, PhMe, M = Pb, Sn M
M
PPh2
PPh2
N
N
Ph2P
Ph2P N
N
TMS TMS
TMSTMS
58
Ph2P
Ph2P N
NTMS
TMS54
ð20Þ
Double deprotonation of 54 with BunLi and then treatment with 2 equiv. of CrCl2(THF)2 wasreported to lead to partially substituted tetranuclear complex 59 (Equation (21)) <1999CC1993>.
i. 2 BunLi, THF; ii. 2 CrCl2(THF)2 THF, 1 day
61%
Ph2P
Ph2P
N
N
Cr
CrClCl
Cr
ClLi(THF)2
Cl
PPh2
N
PPh2
NCr
Cl(THF)2Li
ClTMS
TMS
TMS
TMS
59
Ph2P
Ph2P N
NTMS
TMS54
,
ð21Þ
The dimetallacyclobutane 57 is the first example of a bridging chromium carbene without theusual carbonyl or cyclopentadienyl ligands, and it is also the first example of a chromium carbenecomplex that contains two phosphorus functions on the carbene carbon.
(d) Two phosphorus and two nickel functions. In a study of oxidative addition reactions ofdichlorophosphaalkene 60 with Ni(0) complexes, Konze and co-workers isolated the first exampleof a complex 61 (59–74% yield) with a mixed �2,�4-diphosphaallene ligand that is bridgedbetween two nickel atoms forming a fused, bicyclic heterocycle (Equation (22)) <1998OM1569>.
2 Ni(PPh3)2L + Cl2C=PN(TMS)2PhMe, –50 °C to rt, 1 h
L = (C2H4), 74%; (COD), 69%; (PPh3)2, 59%
NiCl Cl
PPh3Ph3P
(TMS)2N
PPh3P
Ni
61
60
ð22Þ
Treatment of the bicyclic complex 61 with 2 equiv. of triethylphosphine at �40 �C led tosubstitution of the PPh3 groups on nickel by PEt3, but the newly formed complex 62 was unstableand could not be isolated (Equation (23)).
Functions Containing at Least One Group 15 Element 365
NiCl Cl
PEt3Et3P
(TMS)2N
PPh3P
Ni
62
613 PEt3, THF, –78 to –40 °C, 15 min
Not isolated ð23Þ
(iii) Two phosphorus, one metal, and one silicon functions
In a study similar to that described in Section 6.12.3.1.2.(i).(c), Konze and co-workers<1998OM5275> treated dichlorophosphaalkene 60 with a Pd(0) complex and isolated the firstexample of a complex, 63, with a phosphinio-methylene(imino)metallophosphorane ligand �2-coordi-nated to one palladium center and �1-coordinated to another in a dinuclear complex (Equation (24)).
2Pd(PEt3)4 + 60 P
Pd
NTMS
ClEt3P
PdPEt3
TMS
Cl
Et3P
Hexanes, 0 °C to rt, 15 min
57%
63
ð24Þ
Treatment of complex 63 with 3 equiv. of either iodomethane or sodium iodide afforded asimilar complex, 64, in 24% yield. Hydrolysis of complex 63 afforded another novel, three-membered heterocycle, 65 (Scheme 11).
The only recent synthesis of a compound with a carbon bearing one phosphorus, one lithium,and one silicon function was that of the first coligand-free diphosphinomethanide, 67, afforded incrystalline form, by the reaction of silyl substituted phosphinomethane 66 with BunLi(Equation (25)) <B-1996MI187>. The crystal structure of this trimeric compound showed eachlithium atom surrounded by two phosphorus atoms and one carbon atom, with two of the lithiumatoms displaying weak lithium–phenyl contacts.
Me2PPhMe2Si
Me2PH
BunLi Me2PPhMe2Si
Me2PLi
66 67
–BuH1/3
3ð25Þ
6.12.3.1.3 One phosphorus, two silicon, and one arsenic functions
Only two compounds of this description were prepared recently; both are phosphaarsiranes.Treatment of metalloarsane (�5-C5Me5)(CO2)FeAs(TMS)2, 68, with 1 equiv. of [bis(trimethyl-silyl)methylene]chlorophosphane gave 1-metallo-1-arsa-2-phosphapropene 69 and a few crystalsof dimetallophosphaarsirane 70 (Equation (26)) <1996CB219>.
Fe
As(TMS)2OC
OC ClP C(TMS)2+THF, –15 °C to rt, overnight
69, 88%; 70, traceFe As
OC
OC
TMS
P
C(TMS)2P As
TMS TMS
[Fe][Fe]
+
68 69 70[Fe] = [(η5-C5Me5)(CO)2Fe]
ð26Þ
P
Pd
NTMS
IEt3P
PdPEt3
TMS
I
Et3PPd
P
TMSPEt3Cl
Et3P ONHTMS
64
3 MeI, THF, rt, 24 h
24%
H2O, THF, rt, 5 min
82%63
65
Scheme 11
366 Functions Containing at Least One Group 15 Element
The 1-arsa-2-phosphapropene 69 was treated with an excess of [(Z)-cyclooctene]Cr(CO)5 andthe resulting product was purified by chromatography on Florisil followed by crystallization toafford crystalline phosphaarsirane 71 in 17% yield (Equation (27)).
69 As P
[Fe] TMS
TMS
H
Cr(CO5)
i. [(Z )-cyclooctene]Cr(CO)5, n -pentane, 20 °C, 2 days; ii. SiO2/H2O
17%
71
ð27Þ
6.12.4 METHANES BEARING ONE GROUP 15 ELEMENT AND METALLOIDAND/OR METAL FUNCTIONS
6.12.4.1 Nitrogen Functions
6.12.4.1.1 One nitrogen and three boron functions
Since 1995, only one report has appeared that describes the preparation of compounds bearingnitrogen and three boron functions.
By reacting sterically hindered isocyanide ButNC with [anti-B18H22] in benzene, cluster carbon-atom insertion occurred yielding macropolyhedral carbaboranes [7-(ButMeHN)-(anti)-B18H20]and [9-(ButNH2)-(anti)-9-B17H19-8-(CN)] in 6% and 12% yields, respectively <1995CC2407>.These compounds were characterized by MS and NMR spectroscopy; the latter compound wasfurther characterized by single-crystal X-ray diffraction analysis.
6.12.4.1.2 One nitrogen and three silicon functions
A few compounds with a carbon bearing nitrogen and three silicon functions have appeared since1995. All feature trimethylsilyl substituents with the nitrogen as part of an isothiocyanate moietyor a heterocyclic system.
As a promising building block for heterocyclic syntheses, tris(trimethylsilyl)methyl isothiocya-nate was prepared in 95% yield by a novel, direct lithiation of methyl isothiocyanate at �95 �Cusing LDA and trapping of the carbanion intermediate with excess TMSCl/THF (Equation (28))<1997S423>. The product was characterized by its melting point as well as IR and 1H NMRspectra.
MeN C S +LDA (3 equiv.)
THF, Et2O, hexane, –95 °C95%
N C S(TMS)3C3TMSCl ð28Þ
As part of a synthetic exploration of the Peterson olefination route to 1-(1-alkenyl)benzotriazoles,1-(trimethylsilylmethyl)benzotriazole, 72, was lithiated at the �-carbon using LDA, and the result-ing lithiated species was trapped with TMSCl affording 1-bis(trimethylsilyl)methyl-1H-benzotri-azole, 73, in 83% yield (Scheme 12). Further treatment of the latter compound with LDA andtrapping with TMSCl afforded 1-tris(trimethylsilyl)methyl-1H-benzotriazole, 74, and 4-tri-methylsilyl-1-tris(trimethylsilyl)methyl-1H-benzotriazole, 75, as crystalline compounds in 44% and41% yields, respectively. These compounds were characterized by elemental analysis and NMRspectroscopy (1H, 13C). While Peterson olefination on other silylated benzotriazole derivatives wascarried out, no further exploration on compounds 74 and 75 was reported <1999T11903>.
Photolysis of 1,3-bis(trimethylsilyldiazomethyl)-1,1,3,3-tetramethyl-2,2-diphenyltrisilane,76, in cyclohexane with a high-pressure mercury lamp at 0 �C afforded the five-memberedheterocycle 79 in 11% yield (Scheme 13). The structure of this compound was establishedspectroscopically (1H, 13C, 29Si NMR) as well as by elemental analysis, exact mass determi-nation by high-resolution mass spectrometry (HRMS), and X-ray crystallographic analysis.It was suggested that this heterocycle is the hydrolysis product of the bicyclic azo compound78 produced from intramolecular [2+3]-cycloaddition of diazosilene 77. Photolysis of
Functions Containing at Least One Group 15 Element 367
1,4-bis(dimethylphenylsilyldiazomethyl)-1,1,2,2,3,3,4,4-octamethyltetrasilane, 80, in cyclohex-ane afforded compound 82 in 25% yield, and is believed to have formed from nitrogenextrusion of the bicyclic azo compound 81 (Scheme 14) <1995JOM(499)99>.
Silaethene Ph2Si¼C(TMS)2, 83, a product of thermal elimination of LiX (X=Br, F) fromPh2SiX�CLi(TMS)2 and its rearranged form 84, produced upon interaction of 83 with LiBr, under-went [3+2]-cycloaddition with azidodi-t-butylmethylsilane as well as azidotri-t-butylsilane in diethylether at �78 �C affording cycloadducts 85–87 (Scheme 15) <1995CB1231>.
TMS SiMe2
Ph2Si
SiMe2
TMS
N2 N2
Ph2SiMe2Si
SiMe2
TMS
NN
TMS
hν
Me2Si NNPh2Si
Me2Si TMS
TMS
NN
SiMe2
Me2Si SiPh2
TMS
TMS
H2O
H2OHNSiMe2N
TMS
SiPh2Me2(HO)Si
TMS
76
[2 + 3]
Cyclohexane, 4 h
77
79
78
Scheme 13
PhMe2Si SiMe2Ph
N2 N2
(SiMe2)4
Me2SiMe2Si
Me2Si
SiMe2Ph
SiMe2
NN
PhMe2Si
hν [2 + 3]
Me2Si
Me2Si
SiMe2
Me2Si
N
PhMe2Si
SiHMe2PhN
SiMe2
SiMe2
Me2Si
Me2Si
PhMe2Si
PhMe2Si
–N2
80
81
82
Scheme 14
NN
N
TMS
LDA / TMSCl, –78 °C
83% NN
N
TMSTMS
LDA / TMSCl, –78 °C
NN
N
TMSTMS
+N
NN
TMSTMSTMS TMS
TMS72 73
74 75
Scheme 12
368 Functions Containing at Least One Group 15 Element
6.12.4.1.3 One nitrogen, two silicon, and one metal functions
There is a single report of such a compound since 1995. [3+2]-Cycloaddition of the labilestannaethene 88 with But2MeSiN3 at �78 �C afforded the triazoline cycloadduct 89 (Scheme 16)<B-2000MI106>. This compound is a suitable source of the thermolabile stannaimineMe2Sn¼NSiBut2Me.
6.12.4.1.4 One nitrogen and three metal functions
(i) One nitrogen and three chromium functions
There appears to be only one report of a compound belonging to this class since 1995. Cother-molysis of the thiocarbenoid complex CpCr(CO)2(SCNMe)2, 90, with [CpCr(CO)3]2 afforded afour-component mixture which, after column chromatography on silica gel, yielded a dark brownsolid, Cp4Cr4S2(CO)(CNMe2), in 36% yield as a highly air-sensitive compound. This compoundwas characterized by 1H NMR and IR spectroscopy, MS, and single-crystal X-ray diffractionanalysis revealing it as a �3-aminocarbyne cubane complex 91 (Equation (29)) <2002OM4408>.All six Cr�Cr bonds in compound 91 are not shown for clarity.
CrOC CO
CrOC CO
CO
2 Cr SOC
OC N MeMe
H
+ Toluene, 110 °C, 3 h
36%
Cr
SCr
Cr
Cr
SN
O
Me
Me
+ . . .
90 91
ð29Þ
(ii) One nitrogen and three ruthenium functions
Two reports on compounds bearing one nitrogen and three ruthenium functions have appearedsince 1995.
The organometallic cluster H3Ru3(CNMeBz)(CO)6(PPh3)3 was prepared in 77% yield by treat-ment of a cyclohexane solution of HRu3(CNMeBz)(CO)10 with PPh3 and heating the mixture in thepresence of hydrogen gas bubbled through the solution. Chemical oxidation of this cluster withAg+ or ferricenium produced the 47-electron cation [H3Ru3(CNMeBz)(CO)6(PPh3)3]
1+ which was
Ph2Si C(TMS)2
83
+ LiBr_83 . LiBr Me2Si
TMS
SiMePh2
. LiBr+ LiBr_
Me2SiTMS
SiMePh2
NN
NC(TMS)2Ph2Si
But2MeSi
NN
NC(TMS)2Ph2Si
But3Si
NN
NPh2Si
But3Si
TMSSiMePh2
But3SiN3
But3SiN3
But2MeSiN3
84
85 86 87
Scheme 15
Me2Sn C(TMS)2
Br Br
PhLi Me2Sn C(TMS)2
Br Li–LiBr Me2Sn C(TMS)2
NN
NSn
TMSTMS
But2MeSi
MeMe
But2MeSiN3
–78 °C 88
89
Scheme 16
Functions Containing at Least One Group 15 Element 369
characterized spectroscopically (EPR, 1H, 31PNMR, IR). An account of cyclic voltammetricexperiments on this cluster has been detailed <1998OM872>. An investigation on the mechanisticdecomposition of the 47-electron cationic cluster, generated by chemical or electrochemical oxida-tion of the 48-electron precursor, has also been reported. In connection with this study, severalclusters featuring a tetracoordinated carbon bearing nitrogen and three ruthenium functions wereprepared <2001JOM(633)51>. These included H3Ru3(CNMeBz)6L3 (L=PPh3, SbPh3), preparedby previously published procedures <1998OM872, 1990IS196>, and H3Ru3(CNEtBz)6(PPh3)3,H3Ru3(CNMeBz)6(PPh3)2(CNBz), prepared using analogous procedures by substitution of appro-priate ligands on the parent carbonyls. No further preparative details were provided, but IRand 1HNMR data for the latter compounds were reported.
(iii) One nitrogen, two cobalt, and one iron functions
A few compounds having this structural unit have been described since 1995. Clusters of the type93 were generated upon cleavage of the �2-isothiocyanate ligand in [Fe(PPh3)2(CO)2(�
2-SCNR)],92, by 2 equiv. of [Co(�-Cp)(PPh3)2] (Equation (30)) <1999JOM(573)109>. While the cluster withR=MeC(O) decomposed during reaction work-up, others were obtained in good yields.
PPh3
FeOC
OCPPh3
S
N R
CoPh3P PHPh3
2+Co
CoFe
SCO
NR
CO
PPh3
Benzene, 5 h
65–70%
92 93R = Ac, PhC(O), Me2N– C6H4–C(O)
ð30Þ
Except when R=Me2N�C6H4C(O), reaction of clusters 93 with CF3SO2OMe afforded salts94 in which the CNFeCo2 moiety was retained. All the clusters were characterized by their IR and1H NMR spectra. The crystal structure of cluster 94 with R=PhC(CO) was also studied byX-ray diffraction analysis.
Co
CoFe
SCO
NR
CO
PPh3
94
Me+
(iv) One nitrogen and three osmium functions
Numerous reports describing the preparation, reactivity, and crystal structures of various tri-osmium clusters having a carbon bearing one nitrogen and three osmium functions have appearedin the literature since 1995. All clusters described contain a triosmium alkylidyne metal corelinked to a nitrogen function at an apical position.
Triosmium alkylidyne cluster 96 was synthesized by the reaction of 95 with 1 equiv. of DBU inthe presence of a 10-fold excess of 4-vinylpyridine (Equation (31)) <1995MI311>. Treatment ofcluster 96 with a slight excess of [Os3(CO)10(NMe)2] in refluxing n-hexane for 8 h produced thehomonuclearly linked cluster 97 in 34% yield, while reaction of 96 in refluxing CH2Cl2 with tracesof water, using stoichiometric amounts of Wilkinson’s catalyst RhCl(PPh3)3, afforded a 29% yieldof 98 <1995JOM(493)229>.
370 Functions Containing at Least One Group 15 Element
Cl
Os
Os Os
H H
H
4-Vinylpyridine, DBU
CH2Cl2, 0 °C, 0.5 h 69%
N
Os
Os Os
H H
9596
ð31Þ
N
Os
Os Os
H H
O
98
N
Os
Os Os
H H
97
H H
OsOs
Os
HMe
Following the same methodology as that used for the preparation of 96, reaction of 95 withpyridine-containing ligands 99, 100 <1995JCS(D)1379>, 101, 102 <1995ICA(234)5,1995JCS(D)3995>, 103, 104 <1996JCS(D)1853>, 105 <1996JCS(D)2293>, 106, 107, and 108<1999JOM(584)48> afforded moderate-to-good yields of structurally similar complexes.
N
N
N
N
101 102
Fe
N
99
N
100
NFe
N N
103 104
N
N
105
OC16H33
Functions Containing at Least One Group 15 Element 371
N
N
106
R
R = H, CMe3, NH2, NMe2, SMe, OMe, OC6H13, OC7H15, OC9H19, Br, Cl
N
107
OMe
N
108
O2N
Treatment of an ethereal solution of the triosmium cluster 109 with an excess of diazomethaneafforded the diazomethylidyne complex 110 (Equation (32)). The structure of this compound wasestablished based on its analytical and spectroscopic data and was further characterized by single-crystal X-ray crystallography <2000OM5623>.
PhP
Os
OsOsP Ph
Ph
H
CH2N2, Et2O
CH2Cl2, –10 °C, 1 h
40%
P
Os
OsOsP Ph
PhH
H
NN PhPh
109 110
ð32Þ
6.12.4.2 Phosphorus Functions
By far, the greatest number of reports since 1995 of compounds possessing a carbon bearing onephosphorus and three metalloid and/or metal functions is for those with one phosphorus andthree silicon functions. A few examples have been reported of compounds with a carbon bearingone phosphorus and either three transition metals, or one silicon and two metal functions.
6.12.4.2.1 One phosphorus and three metalloid functions
(i) By nucleophilic exchange of chlorine atoms on a silicon atom
Two equivalents of phosphinomethanide 111 reacted with various chlorosilanes generating phos-phorus ylides 112 with a tetraheteroatom-substituted methane functionality <B-1996MI187>.When the reaction was carried out in a 1:1 ratio where R=Ph and R0=Cl, phosphorus ylide 112was obtained in an impure form along with tetraheteroatom-substituted methane 113 resultingfrom monosubstitution on silicon (Equation (33)) <1995JOM(501)167>.
Cl SiR
R1
Cl + n {Li[C(PMe2)(TMS)2]}2.TMEDA Si
PMe2PTMS
TMS
R1 R TMS
TMSMe Me
R = R1 = Me; R = R1 = Cl; R = Ph, R1 = Cl
111
112
+ PhCl2SiPMe2
TMSTMS
113
ð33Þ
372 Functions Containing at Least One Group 15 Element
(ii) By nucleophilic exchange of chlorine atoms on a phosphorus atom
Tris(trimethylsilyl)methyllithium was reported to effect nucleophilic displacement of chlorine onthe phosphorus atoms of chloro-substituted iminophosphane 114 <1997CC293> and 1-chloro-1H-phosphirene 115 <1997CB711>, affording the corresponding products 116 and 117 in 76% and90% yields, respectively (Scheme 17).
The first reports outlining the preparation of diphosphenes (TMS)3CP¼PC(TMS)3<1982TL4941> and (2,4,6-But)C6H2P¼PC(TMS)3 <1983JA1655> by reductive coupling ofthe corresponding alkyldichlorophosphines appeared in the early 1980s, but more recent reportsdescribe further transformations at the phosphorus–phosphorus double bond, including [2+1]cycloadditions with dichlorocarbene <B-1996MI128> and isonitriles <1998JFC(89)73,1999ZAAC1934>; each of these transformations left the tetrasubstituted carbon atom unchanged.
(iii) By reaction of carbon–phosphorus double bonds
P-Halogeno-, P-phenyl-, and P-phosphanyl-substituted 2,2-bis(trimethylsilyl)-1-phosphaethenes,118, have been reported to react with C¼P cleavage to afford compounds possessing a carbonbearing one phosphorus and three silicon functions, or a carbon bearing one phosphorus, onegermanium, and two silicon functions.
When a phosphanyl-substituted phosphaethene (118; X= (�5-1,3-But2C5H3)(CO)2Fe P(TMS))was treated with an excess of [(Z)-cyclooctene]Cr(CO)5, the 1,2-diphosphaferrocene pentacarbo-nylchromium adduct 121 was obtained in low yield along with the butterfly complex 119 and themetallodiphosphene 120, the latter two being too unstable to isolate and only identified by31P-NMR data in comparison with those of related compounds (Equation (34)) <1995CB665>.
ButBut
XP C(TMS)2[Fe] P
Cr(CO)4
PC(TMS)3 P P
[Fe]C(TMS)3
P POTMSTMSO
OTMS
Fe Cr(CO)5
LCr(CO)5+ +
118 119 120 121
L = (Z )-cyclooctene
[Fe] = (h5-1,3-But2C5H3)(CO)2Fe
X = (η5-1,3-But2C5H3)(CO)2Fe–P(TMS)
ð34Þ
Treatment of P-halogenophosphaethenes (118; X=Cl, Br, I) with an equimolar amount ofhexadichlorosilane effected C¼P cleavage and P¼P formation, giving diphosphene 122 in 71%yield when X=Cl <B-1998MI286, 1994JOM(475)95>. By following the reaction by 31P-NMR,the authors postulated the intermediacy of the phosphaalkene (TMS)2C¼PSiCl3, which then
ClP N
TMSTMS
TMSLi
P
But
Ph
Cl
Et2O, 90%P
But
Ph
TMSTMS
TMS
P NTMSTMS
TMSTHF, –78 °C, 76%
114
116
115
117
Scheme 17
Functions Containing at Least One Group 15 Element 373
dimerizes by 1,2-addition of the P�Si bond of one molecule to the C¼P bond of another to give(TMS)2C¼P-P(SiCl3)C(TMS)2SiCl3, followed by a 1,2-trichlorosilyl shift from phosphorus tocarbon, thereby affording diphosphene 122 (Equation (35)).
P PC(TMS)2SiCl3
Cl3Si(TMS)2C71%
Si2Cl6, hexanes, 60 °C, 8 days; X = Cl
122118
XP=C(TMS)2 ð35Þ
In their studies of group 14 carbene analogs and their reactions with P-phosphanyl phosphaalk-enes, du Mont and co-workers observed a similar type of transformation when phosphaethene 122(X=PPri2) was converted to diphosphene 123 (83% yield) upon treatment with the silylene SiCl2;the latter was generated in situ by an �-elimination of Me3GeCl from Me3GeSiCl3, induced by thedialkylphosphanyl group within phosphaethene 118 (Equation (36)) <2002AG(E)3829>.
The same research group also investigated the reactivity of phosphaethene 118 (X=PPri2) withGeCl2-dioxane, observing the formation of diphosphene 124 by 31P-NMR and isolating acrystal suitable for low-temperature X-ray diffraction analysis; however, the major isolated productwas the fused bicyclic heterocycle 125, which possesses two carbons that each bear one phosphorus,one germanium, and two silicon functions (�50% yield) (Equation (37)) <2001MI609>.
P P
(TMS)2C
C(TMS)2Cl2Si
SiCl2PPr i
2Pr i2 P
Me3GeSiCl3; X = PPr i2
83%
123
118
XP=C(TMS)2ð36Þ
P P
(TMS)2C
C(TMS)2Cl3Ge
GeCl2PPr i2
(TMS)2C PPCl2Ge
GeCl2
C(TMS)2GeCl2; X = PPr i
2
50%
124 125
–(Pr i2 P)2GeCl2
–Pri2 PCl
118
XP=C(TMS)2 ð37Þ
In another recent study of the reaction of silylenes and germylenes with phosphaalkenes, Kimel et al.<2001MC85> described the reaction of phosphaethene 118 (X=Ph) with MMe2 (M=Si, Ge)affording the corresponding unstable phosphasilacyclopropane (126, M=Si) and phosphogermacy-clopropane (126, M=Ge), respectively; the former generated as part of a gross mixture of otherphosphorus-containing products and identified only by a 31P-NMR signal at � �132.4; the latterobtained cleanly and characterized by 1H, 13C, 31P, and 29Si NMR analysis. Further reaction of 126(M=Ge) with GeMe2 gave the 2,3-digerma-1-phosphacyclobutane 127 (Equation (38))<2002MI1568>.
MMe2
MMe2
PPhTMS
TMS Me2Ge GeMe2
PPhTMS
TMSGeMe2; M = Ge
118X =Ph; M = Si, Ge
126 127
XP=C(TMS)2 ð38Þ
6.12.4.2.2 One phosphorus and three metal functions
The only reports since 1995 of compounds of this description involve organometallic complexeswith carbons bearing, in addition to one phosphorus function, either three osmium functions orthree cobalt functions. All of the reported syntheses of the former complexes involve C�P bondformation upon displacement of chlorine from carbon bearing three osmium functions, and thesole reported synthesis of the latter involves C�Co bond formation by displacement of chlorinefrom a carbon bearing one phosphorus function.
The reaction of the triosmium alkylidene cluster [Os3(�-H)3(CO)9(�3-CCl)], 128, with variousbidentate diphosphine ligands is outlined in Scheme 18. Cluster 128 reacted with an excess ofbutyldiphenylphosphine in the presence of a stoichiometric amount of DBU to give the expectedcomplex 129 in 30% yield. A similar reaction was observed with the optically active diphosphine130, affording a mixture of isomeric complexes 131 and 132 in 15% and 20% yields, respectively.Complex 131 decarbonylated at room temperature after 24h to give an octacarbonyl homometallic
374 Functions Containing at Least One Group 15 Element
cluster 133 in 50% yield. The isomeric complex 132 failed to cyclize under similar conditions,perhaps due to potentially unfavorable steric interactions in the corresponding six-membered ring<1995JCS(D)2831> (Scheme 18).
Complexes 135 (45% yield) and 136 (50% yield) were formed in a similar way from the reaction of128 with the bidentate ligands Ph2PCH2PPh2 and Ph2PCH2CH2PPh2, respectively, (Scheme 19)<1996JOM(518)227>. Both subsequently decarbonylated and cyclized to form five- and six-memberedosmacyclic complexes 137 (60% yield) and 138 (40% yield), respectively, whereas treatment of cluster128 with the homologous ligand Ph2PCH2CH2CH2PPh2 led to an acyclic, linking complex 139.
Os Os
H H
H
Os
Cl
Os Os
H HOs
PPh2Bu
Ph3PPPh2
HMe
Os Os
H HOs
Ph2P
PPh2HMe
Os Os
H HOs
Ph2PPPh2
H Me
Os Os
H HOs
Ph2P
PPh2
H
Me
Os Os
H HOs
P
PPh2
MeH
, DBU
BuPPh2, DBU
128
129
132 134
131 133
30%
PhPh
131, 15%; 132, 20%
50%
CH2Cl2, 24 h
130
Scheme 18
128
Os Os
H HOs
Ph2P
PPh2
137
Os Os
H HOs
PPh2CH2PPh2
135
Os Os
H HOs
PPh2
139
Os Os
H HOs
PPh2
Os Os
H HOs
Ph2P
PPh2
138
Os Os
H HOs
PPh2CH2CH2PPh2
136
Ph2PCH2PPh2, DBU
Ph2PCH2CH2PPh2, DBU
Ph2PCH2CH2CH2PPh2, DBU
CH2Cl2, 2 days
CH2Cl2, 2 days
50%
45%
40%
60%
40%
Scheme 19
Functions Containing at Least One Group 15 Element 375
The ferrocenyl-phosphine cluster derivative 140 was prepared in a similar fashion by thereaction of cluster 128 with 1,10-bis(diphenylphosphino)ferrocene (Equation (39))<1995JCS(D)1379>.
Ph2PPh2P
Fe
PPh2
Fe
PPh2
Os
Os
H
H
Os128 +DBU, CH2Cl2, 30 min
32%
140
ð39Þ
The formation of a tricobalt carbonyl cluster (141; R=Et) was accomplished by treatment of[Co2(CO)8] with Cl3CP(O)(OEt)2 (Equation (40)) <1997JOM(541)417>. A similar complex (141;R=TMS) was also prepared either by treatment of [Co2(CO)8] with Cl3CP(O) (OTMS)2 or byreaction of 141 (R=Et) with TMSBr (in 15% yield for the latter). The Lewis donor ability of theP¼O function of cluster 141 (R=Et) was used to assemble early-late metal systems by reactionwith [Cp2MCl]+ (M=Ti, Zr).
(OC)3Co Co(CO)3
Co(CO)3
(RO)2P
141
O
Cl ClCl
(RO)2P
O
+ Co2(CO)8
THF, 50 °C, 3 h
28%, R = Et;23%, R = TMS
ð40Þ
6.12.4.2.3 One phosphorus, one silicon, and two metal functions
Two reports describing the preparation of compounds of this type have appeared since 1995; onedescribing a symmetrical complex with two carbons each bonded to one phosphorus atom, onesilicon atom and two rhodium atoms, and a second outlining a structural investigation of adilithiated phosphonate with a carbon bonded to one phosphorus atom, one silicon atom and twolithium atoms.
Photolysis of rhodium-substituted triethylsilyldiazomethyl complex 142 led to the dimer 143,most likely via the intermediacy of a transient rhodium-stabilized carbene (Equation (41))<1996OM1166>.
Rh RhPEt3
PEt3Et3P
Et3P
PEt3
TMS
TMS
Et3P
(Et3P)3RhN2
TMS
Benzene, 25 °C, 90 min, hν = 330 nm
Unstable > –20 °C
143142
ð41Þ
Treatment of a solution of dimethyl(trimethylsilylmethyl)phosphonate in TMEDA at �78 �Cwith 2.5 equiv. of BunLi gave the crystalline dilithiated phosphonate 144, whose X-ray crystalstructure revealed a highly aggregated species that is characterized by a Li�O�Li�O four-membered ring at its core (Equation (42)) <1999AG(E)92>.
(MeO)2P TMS
O
(MeO)2P TMSO
Li Li3
N(Me)2
2
(Li+. (TMEDA)2) . (TMEDA)
2
i. 2.5 BunLi, TMEDA, –78 °C;
ii. rt, 24 h
144
. .–
ð42Þ
376 Functions Containing at Least One Group 15 Element
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378 Functions Containing at Least One Group 15 Element
Biographical sketch
Shahrokh Saba was born in Tehran, Iran, stu-died at the American University of Beirut, inLebanon where he obtained his B.S. in 1970.He continued his education at the Universityof East Anglia and received his Ph.D. in 1974under the direction of ProfessorA. R. Katritzky. During 1975–1979 he taughtas an Assistant Professor at Azad Universityin Tehran. He moved to the United Statedin 1980 and after postdoctoral fellowships in1980 (Professor R. Breslow, Columbia Uni-versity), 1981 (Professor W. C. Agosta,Rockefeller University), and 1982–1983 (Pro-fessor N. O. Smith, Fordham University)assumed a teaching position at Kean College,New Jersey in 1984. He returned to FordhamUniversity in 1986 and took up his presentposition, and is currently an Associate Pro-fessor of chemistry. His scientific interestsinclude all aspects of heterocyclic chemistry,and new uses of simple ammonium salts inorganic synthesis.
James A. Ciaccio was born in Newburgh, NY,studied at SUNY, Oneonta where he obtaineda B.S. in chemistry. His graduate studies inorganic chemistry were conducted at SUNY,Stony Brook, where he obtained a Ph.D.under the direction of Professor T. W. Bell.In 1989 he was awarded a Camille and HenryDreyfus Postdoctoral Teaching and ResearchFellowship at Bucknell University, where hewas Visiting Assistant Professor of Chemistrywhile working in the laboratories of Prof.H. W. Heine. During 1989–1990 he taught asVisiting Assistant Professor of Chemistry atBard College, after which he took up hispresent position at Fordham University,where he is currently Associate Professor ofChemistry and Director of the GeneralScience Program. His scientific interests fallin the general area of organic synthetic meth-ods with emphasis on reactions and synthesisof epoxides and other heterocycles. He hasalso published several novel undergraduateorganic laboratory experiments that combinesynthesis and mechanistic discovery.
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Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 355–379
Functions Containing at Least One Group 15 Element 379
6.13
Functions Containing at Least One
Metalloid (Si, Ge, or B) and No
Halogen, Chalcogen, or Group 15
Element; Also Functions Containing
Four Metals
P. D. LICKISS
Imperial College London, London, UK
6.13.1 METHANES CONTAINING AT LEAST ONE METALLOID (AND NO HALOGEN,CHALCOGEN, OR GROUP 15 ELEMENT) 382
6.13.1.1 Methanes Bearing Four Metalloid Functions 3826.13.1.1.1 Four similar metalloid functions 3826.13.1.1.2 Three similar and one different metalloid functions 3876.13.1.1.3 Two similar and two different metalloid functions 388
6.13.1.2 Methanes Bearing Three Metalloid Functions and a Metal Function 3896.13.1.2.1 Three similar metalloid functions 3896.13.1.2.2 Other mixed metalloid functions 401
6.13.1.3 Methanes Bearing Two Metalloid and Two Metal Functions 4026.13.1.3.1 Two Si and two metal functions 4026.13.1.3.2 Two Ge and two metal functions 4026.13.1.3.3 Two B and two metal functions 4026.13.1.3.4 Other combinations of two metalloids and two metal functions 403
6.13.1.4 Methanes Bearing One Metalloid and Three Metal Functions 4036.13.1.4.1 One Si and three metal functions 4036.13.1.4.2 One Ge and three metal functions 4036.13.1.4.3 One B and three metal functions 403
6.13.2 METHANES BEARING FOUR METAL FUNCTIONS 4036.13.2.1 Methanes Bearing Four Similar Metals 4036.13.2.2 Methanes Bearing Three Similar and One Different Metal Functions 4036.13.2.3 Methanes Bearing Two Similar and Two Different Metal Functions 4046.13.2.4 Methanes Bearing Four Different Metal Functions 404
6.13.3 METHANES BEARING MORE THAN FOUR METALLOIDOR METAL FUNCTIONS 404
381
6.13.1 METHANES CONTAINING AT LEAST ONE METALLOID (AND NO HALOGEN,CHALCOGEN, OR GROUP 15 ELEMENT)
The structure of this chapter is based closely on the corresponding one in COFGT (1995), whereit was noted that for the 47 different elements (i.e., not the elements specifically excluded in thetitle of the section, the lanthanides, the actinides, and Fr, Ra, and Tc) that were to be consideredas substituents at a quaternary carbon, there are 230 300 different possible combinations of themetal substituents (not including a further 178 365 optical isomers generated by having fourdifferent elements as substituents). The number of these possible combinations discussed later isstill below 0.1% of those possible thus indicating that there is still tremendous scope for thesynthesis of such organometallic compounds. For the case of methanes bearing four metalsubstituents, it has been necessary to make some judgment about whether the species may be ofinterest to organic chemists. For example, compounds where the carbon is part of a metal carbidehave been excluded.
6.13.1.1 Methanes Bearing Four Metalloid Functions
There are hundreds of compounds known containing a carbon substituted by four silyl groups.The many methods to prepare them have not developed much beyond those described in COFGT(1995), but some new variations of reagents and experimental conditions mean that yields areoften improved. The surprising lack of compounds with no tetragermyl substitution at carbonwas noted in COFGT (1995). Although this is no longer the case, very few compounds of thistype are known even now. This is still presumably due to a lack of synthetic effort as many of themethods available for tetrasilylmethane synthesis should be suitable for the preparation oftetragermylmethanes. A small number of methanes substituted by four boron functions havebeen prepared and there are an increasing range of compounds containing either a variety ofmetalloid functions or mixed metalloid and metal functions.
6.13.1.1.1 Four similar metalloid functions
(i) Four Si functions
(a) Tetrasilylmethanes from in situ coupling reactions. Symmetrical compounds containing theSi4C function may be prepared by in situ coupling reactions involving CCl4 or CBr4 and a group 1or 2 metal. These reactions are discussed in more detail in <1995COFGT(6)377>. A few newexamples have been reported recently; for example, the use of 4,40-di-t-butylbiphenyl as a catalystin the reaction of CCl4 with lithium powder at low temperature gives an 80% yield of (Me3Si)4C<1996T1797>, which is much better than that without the catalyst. The in situ method has alsobeen used in the preparation of the spirocyclic compound 1 in 25% yield (Equation (1))<1999CL317>. These syntheses rely on the relatively slow coupling reactions to form disilanesusing Li or Mg and should be applicable to a wider range of silanes as long as the substituents arenot too bulky.
SiMe2Cl
SiMe2Cl SiMe2
C
Me2Si
SiMe2
Me2Si
CCl4 Mg
1
+ + ð1Þ
(b) Formation by reaction between a trisilyllithiomethane and a halosilane. The reactionsbetween trisilyllithiomethanes (for their synthesis, see Section 6.13.1.2.1 below) and halosilaneshave been used to prepare a wide range of tetrasilylmethanes in which there are at least twodifferent silyl substituents on the carbon. Such compounds are not accessible via the in situcoupling reaction, which produces only symmetrical compounds. This method is thus moregeneral and often gives good yields. The only potential difficulty with these reactions is that theSi3CLi-substituted precursor may require stringent low-temperature conditions for its preparation.
382 Functions Containing at Least One Metalloid (Si, Ge, or B)
The bulk of a trisilyllithiomethane derivative together with the low-temperature preparationsmeans that it is possible to prepare reagents containing functional groups that would notnormally be compatible in simpler compounds. For example, reagents containing both Si�Hand C�Li groups are accessible and can be used to give a range of compounds containing Si�Hgroups that can then be used as precursors to many other tetrasilylmethanes. The range oftrisilylithium reagents available for these reactions, together with the products available, isgiven in Table 1. As would be expected from simple metathesis reactions, the yields for this methodare usually good. The order in which the silyl substituents are attached to the central carbon may beimportant if the groups are particularly bulky, and it seems best if the most bulky silyl substituent isnot the one to be attached last. It should also be noted that addition of more than 1 equiv. of atrisilylmethyllithium reagent to a polyhalosilane does not result in more than monosubstitution atsilicon; presumably this is due to the steric crowding at the relatively small silicon center. Thereaction of (HMe2Si)3CLi with SiCl4 gives several products (see Table 1), the main one being thecyclic species 2, in approximately 38% yield <1999OM1804>. The generation of compoundscontaining more complicated tetrasilylmethane centers by this general route is exemplified bythe syntheses of the bicyclic compounds 5 and 6 shown in Scheme 1 <1998CL1145,2000JOM(611)12>. In this case, the intermediate organometallic reagent, 4, derived from thetrisilylmethane derivative 3, is probably the potassium derivative in THF solution. In a relatedreaction to those described above, the treatment of the Grignard-like species [Mg(OEt)2{C(Si-Me3)3}I]2 with Me3SiCl gives (Me3Si)4C in 23% yield <2001JOM(631)76>.
(c) Formation via addition reactions of silenes. The dimerization of silenes, Si¼C containingcompounds, occurs readily at room temperature and usually gives head–tail dimers. If there aretwo silyl substituents at the unsaturated carbon center, then the resulting dimers contain twotetrasilylmethane centers. The silenes (Ph2MeSi)(Me3Si)C¼SiMe2 <1996JOM(524)147> and(Me3Si)2C¼SiPh2 <1995CB1241> undergo Ph and Me group migrations to give a mixture ofisomeric silenes that dimerize in the head-to-tail fashion to give the disilacyclobutanes 7–10 invarying yields depending on the nature of the silene starting material. The silene(Me3Si)2C¼SiMe2 dimerizes in a similar manner <2000JOM(598)292>.
(HMe2Si)2C
Me2Si
C(SiMe2H)2SiMe2
Me2Si
Me2Si
Me2Si
C
C
Me2Si
SiMe2
SiMe2
SiMe2R
H
Me2Si
Me2Si
Me2Si
C
C
Me2Si
SiMe2
SiMe2
H
H
Me2Si
Me2Si
Me2Si
C
C
Me2Si
SiMe2
SiMe2
SiMe3
Me3Si
Me2Si
Me2Si
Me2Si
C
C
Me2Si
SiMe2
SiMe2
M
H
2
BuLi/ButOK
THF, – 40 °C
R = Me
i. BuLi/ButOK
ii. Me3SiCl
98%
3 4
56
RMe2SiCl
R = Me, 82%R = Ph, 90 %R = CH2CH2CH2Cl, 86 %
Scheme 1
Functions Containing at Least One Metalloid (Si, Ge, or B) 383
Table 1 Tetrasilylmethanes from the reaction of miscellaneous trisilyllithiomethanes with halosilanes
Lithiomethane Halosilane Product Yield (%) References
R2C(SiMe2Ph)Li PhMeHSiCl R2C(SiMe2Ph)(SiPhMeH) 40 <1998JOM(560)41>R2C(SiPh2Me)Lia Me2SiHCl R2C(SiPh2Me)(SiMe2H) 40 <1995BSF517>
<2001EJI481>R2C(SiPh2Me)Li Me3SiCl R3CSiPh2Me <2001EJI481>R3CLi EtSiCl3 R3CSiEtCl2 <1996JCS(P2)163>R3CLi BunSiCl3 R3CSi(Bu
n)Cl2 <2000JOM(598)222>48 <2000PS(158)97>
R3CLi (p-MeOC6H4)SiCl3 R3CSi(p-MeOC6H4)Cl2 60 <2000PS(158)97>R3CLi (p-MeOC6H4)MeSiF2 R3CSiMe(p-MeOC6H4)F 70 <2000PS(158)97>R3CLi (p-MeOC6H4)2SiF2 R3CSi(p-MeOC6H4)2F 62 <1997JOM(545–546)61>R3CLi Si2Cl6 R3CSi2Cl4CR3 72 <2001IC3766>R3CLi Me3SiCl R4C 82 <2001EJI481>R3CLi Me2SiHCl R3CSiMe2H 82 <2001EJI481>R3CLi CH2¼CHMeSiCl2 R3CSiMeClCH¼CH2 <2000JOM(598)222>R3CLi (p-MeOC6H4)2SiMeHCl R3CSi(p-MeOC6H4)MeH <2000JOM(598)222>
40 <1999PS(149)229>R3CLi (p-MeC6H4)2SiMeHCl R3CSi(p-MeC6H4)MeH <2000JOM(598)222>
45 <1999PS(149)229>R3CLi Ph2SiF2 R3CSiPh2F <2000JOM(598)222>R2C(SiMe2H)Li Me3SiCl R3CSiMe2H 30 <2000OM374>
63 <2001JOM(640)29>R2C(SiMe2H)Li Me2SiHCl R2C(SiMe2H)2 69 <2001JOM(640)29>R2C(SiMe2H)Li Me2PhSiCl R2C(SiMe2Ph)(SiMe2H) 64 <2001JOM(640)29>R2C(SiMe2OPh)Li Me2SiHCl R2C(SiMe2OPh)(SiMe2H) 47 <2001JOM(640)29>R2C(SiMe2SPh)li Me2SiHCl R2C(SiMe2SPh)(SiMe2H) 43 <2001JOM(640)29>R2C(SiMe2SMe)Li Me2SiHCl R2C(SiMe2SMe)(SiMe2H) 31 <2001JOM(640)29>(HMe2Si)3CLi Me3SiCl (HMe2Si)3CR 98 <1999OM1804>(HMe2Si)3CLi MeSiHCl2 (HMe2Si)3CSiMeHCl 91 <1999OM1804>(HMe2Si)3CLi HSiCl3 (HMe2Si)3CSiHCl2 20 <1999OM1804>(HMe2Si)3CLi MeSiCl3 (HMe2Si)3CSiMeCl2 96 <1999OM1804>(HMe2Si)3CLi SiCl4 (HMe2Si)3CSiHCl2
b 26 <1999OM1804>(HMe2Si)3CLi SiCl4 (HMe2Si)3CSiMe2CH(SiMe2H)2
b 8 <1999OM1804>(HMe2Si)3CLi CH2¼CHMe2SiCl (HMe2Si)3CSiMe2CH¼CH2 89 <2001JOM(620)127>(HMe2Si)3CLi CH2¼CHMeSiCl2 (HMe2Si)3CSiMeClCH¼CH2 85 <2001JOM(620)127>(HMe2Si)3CLi CH2¼CHCH2MeSiCl2 (HMe2Si)3CSiMeClCH2CH¼CH2 87 <2001JOM(620)127>(HMe2Si)3CLi [CH2¼CH(CH2)4]Me2SiCl (HMe2Si)3CSiMe2[(CH2)4CH¼CH2] 92 <2001JOM(620)127>(PriMe2Si)3CLi Me2SiHCl (PriMe2Si)3CSiMe2H 77 <1995JOM(489)181>
a R¼ Me3Si.b Formed as a mixture, together with compound 2.
C SiMe2
Me2Si CMe3Si
R2
SiMe3
R2
C SiMe2
Me2Si CR2
Me3Si
SiMe3
R2C SiMe2
Me2Si CR1
R1
SiMe3
R2
C SiMe2
Me2Si CR1
R1
R1
R1
7 8 9 10R1
= SiMe2Ph R2
= SiMePh2
Photolysis or thermolysis of diazomethane precursors gives rise to the silenes 11, which undergointramolecular head-to-tail additions to give the cyclic species 12 in low yield as components ofcomplicated product mixtures (Equation (2)) <1995JOM(499)99>. Reaction of PhSiCl3 with{Li[C(PMe2)(SiMe3)2]}2�xTMEDA occurs to give the phospha-alkene 13, which on prolongedreaction times or on storage gives 14 via a complicated mechanism thought to involve loss ofPMe2Cl, formation of a silene intermediate, and both Me and SiMe3 migrations (Equation (3))<1995JOM(501)167>.
PhMe2Si
Si
SiMe2
SiMe2
SiMe2Ph
Me2
C
SiMe2
C
Me2Si
Me2Si
SiMe2PhPhMe2Sin
n11
n = 1 or 212
( )( )
ð2Þ
Me3SiSi
PSiCl
PhPMe2
C(SiMe3)2
Me3
Me2 Me2Si PMe2
Si(Me3Si)2C
Ph MeSiMe3
1314
ð3Þ
Addition of Me3SiN3 to the THF adduct of the silene (But2MeSi)(Me3Si)C¼SiMe2 leads not toa cycloaddition but the formation (But2MeSi)(Me3Si)2CSiMe2N3 in 15% yield together withdiazo-containing products <1996CB471>. Addition of a lithium reagent to a silene can alsooccur, thus reaction of TsiLi(Tsi=(Me3Si)3C) with the silene (Me3Si)2C¼SiMe2, at �95 �Cfollowed by warming to room temperature and work-up in the air affords (Me3Si)2CHSiMe2Tsi<2000JOM(598)292>.
(d) Thermolytic or photolytic methods. Interest in the thermolysis of low-molecular-weightsilanes to give complicated cyclic compounds has waned in recent years but the thermolysis of(Cl3Si)2CCl2 in a fluidized bed of Si/Cu has been revisited and shown to afford (Cl3Si)4C andthe cyclic compounds 15 and 16 <1994ZAAC(620)136>. Similarly, thermolysis of the trisila-cyclohexane derivative 17 over Si/Cu gives compounds 18 and 19 (Equation (4))<1994ZAAC(620)1253>.
C
Cl2SiSiCl2
CCl3Si SiCl3
Cl2Si SiCl2
C
Cl2Si
CSiCl2
Cl2SiSiCl2
CCl3SiCl3Si
SiCl3SiCl3n
1615
n = 0, 1, or 2
Cl2Si
SiCl2
SiCl2 Cl2Si
SiCl2
CSiCl2
SiCl3SiCl3 Si
Cl2
C
Cl2Si
Cl2SiSiCl2
C
Cl2Si
SiCl2
SiCl2
Cl2Si
Si/Cu
17 18 19
330 °C +ð4Þ
Functions Containing at Least One Metalloid (Si, Ge, or B) 385
(e) Other methods. No recent examples of transition metal catalyzed syntheses or carbosilanerearrangements catalyzed by AlBr3 as methods for preparing tetrasilylmethanes seem to have beenpublished. These methods are discussed in <1995COFGT(6)377>. The reaction between Me3Ge-SiCl3 and phosphaalkenes 20 led to an unusual P¼C bond cleavage and the formation of thecyclic species 21 (Equation (5)) <2002AG(E)3829>.
Me3Si
Me3SiP
PPriR1 C
Cl2SiSiCl2
P PPriR1
Me3SiMe3SiToluene
2 h, rt
2021
R1 = Pri or But
ð5Þ
(ii) Four Ge functions
The surprising absence of tetragermylmethane derivatives was noted in the reference<1995COFGT(6)377> and was attributed to a lack of synthetic effort in this area rather than toany inherent instability of such compounds. More recently, a need for the synthesis of tetragermyl-methanes has been generated by the semiconductor and chemical vapor deposition community andthis has led to the preparation of a small number of these compounds. The synthesis of (BrCl2Ge)4Cand (Br3Ge)4C can be achieved in 80% and 95% yields, respectively, via the insertion of GeX2�dioxane(where X=Cl or Br, respectively) into the C�Br bonds of CBr4 <1998JA6738, 1995IC5103>.Reduction of these perhalo compounds with LiAlH4 gives (H3Ge)4C in 20% yield, which has beenused as a precursor to various semiconductor materials via thermal decomposition <B-1999MI001>.
(iii) Four B functions
Compounds containing the CB4 grouping in which the C�B bonds are simple two-center two-electron bonds are rare, much more common are the polyhedral carboranes where multicenterbonding predominates. This chapter will not discuss carboranes, more information about themcan be found in several reviews <2002CCR(232)173, 2002CCC869, 2000JOM(614)10,1999CCC895>. One of the very few preparations of a tetraboramethane derivative is shown inEquation (6), in which a boriranylideneborane, 22, reacts with tetrahalodiboranes. If the sub-stituents at boron are aryl rather than alkyl, then products containing the CB2Si2 grouping areformed (see Section 6.13.1.1.3) <2001EJI387>.
(Me3Si)2C C
B BBut
But
CBB
CBMe3SiBMe3Si
X
X
But
X
ButX
+ B2X4
Hexane
–85 °C
X = Cl, 92%; X = Br, 82%
22
ð6Þ
Despite the lack of synthetic interest in simple compounds containing the CB4 grouping, therehas been theoretical interest as the computational search for species containing planar four-coordi-nate carbon reveals that the ‘‘boraplane’’ 23 does have a D4h arrangement at the central carbon. Anexperimental confirmation of this planarity does not seem to have been carried out <2001JA994>.
C
B B
BB
23
386 Functions Containing at Least One Metalloid (Si, Ge, or B)
6.13.1.1.2 Three similar and one different metalloid functions
(i) Three Si functions and one Ge function
The ready availability of trisilyllithiomethane derivatives (see Section 6.13.1.2.(i).(a) below) wouldsuggest that the easiest route to Si3GeC compounds is the reaction of a germyl halide with anSi3CLi derivative. The reaction of (Me3Si)3CLi with GeCl4 in THF gives the expected (Me3Si)3C-GeCl3 <1997T12215>, and the reaction of 1 equiv. of (Me3Si)3CLi with GeBr4 in toluene solutionaffords (Me3Si)3CGeBr3 but use of a 2:1 ratio of reagents does not give rise to [(Me3Si)3C]2GeBr2but rather to (Me3Si)3C(PhCH2)GeBr2 in 64% yield. This is thought to be due to a loss of Tsi� fromthe initially formed [(Me3Si)3C]2GeBr2 followed by formation of PhCH2� from the solvent andradical recombination of PhCH2� and (Me3Si)3CGeBr2� <1999ZAAC(625)1807>. Reaction of(Me3Si)3CLi with GeCl2� dioxane in THF solution gives the germylene [(Me3Si)3C]Cl-Ge:�LiCl�3THF in 41% yield, which undergoes ready reaction with alkenes or with phenyl acetyleneto give Ge(IV) products 24 and 25 resulting from (2+1)-cycloadditions (Scheme 2). A novel bicyclicdigermane, 26, is formed on reduction of 25a with Mg/MgBr2 (Scheme 2) <1996OM3103>.Reaction of (Me3Si)2(2-NC5H4Me2Si)CLi with GeCl2� dioxane gives the monomeric organogerma-nium(II) chloride 27 in 72% yield <2001OM1223>. As in the case of [(Me3Si)3C]ClGe:�LiCl�3THF,the usual dimerization expected for such species is prevented by the steric protection afforded by thethree bulky silyl substituents, intramolecular coordination via the pyridyl nitrogen also prevents anincrease in coordination number at the Ge atom. The first structurally characterized organometallicate complex of Ge(II), 28, has been prepared in 40% yield from the reaction of (Me3Si)3CLi withGe(SBun)2 <2002OM4005>.
N
Ge
Me2Si
CMe3SiClMe3Si
27
Ge SS
Li
BuSSBu
CTHF
THF
Me3SiMe3SiMe3Si
28
(ii) Three Si functions and one B function
Relatively few new syntheses of compounds containing the Si3BC grouping were reported in the1990s; most of the recent chemistry of such compounds deriving from compounds preparedbefore COFGT (1995) was published. The most obvious route to Si3BC-containing compoundsis to treat a boron trihalide with a trisilyllithium reagent. Thus, the reaction between (Me3Si)3CLiand BCl3 gives the expected monosubstituted product (Me3Si)3CBCl2. Substitutions at the B�Clbonds may then be carried out to generate further compounds containing the Si3BC grouping<1997JOM(536)361>. A more complicated route has been found to be the addition of a silylene
TsiGe:.LiCl.THF
Cl
HR3
R1
R2
Ge GeCl
TsiCl
Tsi
HR3
R1
R2
Ge GeCl
TsiCl
Tsi
HPh
Ge Ge TsiTsi
HPh
Tsi = (Me3Si)3C
Mg/MgBr2
Ethylene, 25a26, 68%
25a, R1 = R2
= R3 = H
b, R1 = R2
= H, R3 = Me
c, R1 = R2
= H, R3 = Ph
d, R1 = R2
= Me, R3 = H
24
Scheme 2
Functions Containing at Least One Metalloid (Si, Ge, or B) 387
to an unsaturated species. Thus, addition of Me2Si: to Me�B¼C(SiMe3)2 is thought to leadinitially to a three-membered ring, which undergoes further reaction with a second equivalentof Me�B¼C(SiMe3)2 to give ring expansion and the formation of 29 in 77% yield<1995OM1507>.
B BC(SiMe3)2
Me2Si
(Me3Si)2C
MeMe
29
(iii) Three Ge functions and one Si or B function; also three B functions and one Si or Ge function
Considering the dearth of compounds containing the CGe4 function, it is, perhaps, not surprisingthat there are a few trigermylmethyl derivatives known. Only one compound, (Me3Ge)3CSiBu
t2F,
containing the CGe3Si grouping seems to have been prepared. It can be made in 20% yield byreaction of (Me3Ge)2(FBu
t2Si)CLi�2THF with Me3GeCl <1996JOM(511)239>. No doubt many
other derivatives could be prepared in a similar way. No compounds with the CGe3B groupingseem to be known. Again, this lack of compounds is not likely to be due to a problem of inherentinstability of such species but rather a lack of interest in their synthesis. Apart from the silyl- andgermyl-substituted carboranes, there is a lack of CB3Si or CB3Ge functions, which is surprisingwhen one considers that several compounds containing the CB4 function are known (see Section6.13.1.1.1). However, the first triboracyclobutane 30 can be prepared according to Equation (7)from the triboracyclobutanide 31 in 50% yield <2003AG(E)669, 2003AG(E)671>. The synthesisof these mixed metalloid compounds could probably be easily achieved in a manner similar tothose already known, i.e., via metathetical reactions between a metalloid-substituted methyl-lithium derivative and an element halide.
B
C
B
BCH2SiMe3
DurDur
Me3Si
Li
C
BBB Dur
CH2SiMe3B
Dur
SiMe3
ClMe3SiCH2
–LiCl+ Cl2BCH2SiMe3
Dur = duryl, 2,3,5,6-Me4C6H31 30
ð7Þ
6.13.1.1.3 Two similar and two different metalloid functions
(i) Two Si and two Ge functions
When one considers that there are a large number of compounds containing the CSi4 functionand a few CGe4 function known, it might be expected that there will only be a handful ofcompounds known that contain the CSi2Ge2 function. This is indeed the case. Such compoundshave been prepared using methods that have been widely used for the synthesis of CSi4 functionsand many more species could no doubt be prepared in similar ways. Little work has been donewith these compounds since that reported in <1995COFGT(6)377>, but more examples of theelimination of LiX from XMe2GeCLi(SiMe3)2 compounds (where X=F, Br, OMe, or OPh) togive Me2Ge¼C(SiMe3)2, which dimerizes to give the head-to-tail dimer [Me2Ge�C(SiMe3)2]2,have been reported <2000JOM(598)292, 2000JOM(598)304>.
(ii) Two Si, one Ge, and one B functions
Compounds containing the CSi2GeB function do not appear to be known. They are likely,however, to be readily available from the reaction of one of the several known CSi2GeLi contain-ing compounds with a boron halide or B(OMe)3.
388 Functions Containing at Least One Metalloid (Si, Ge, or B)
(iii) Two Si and two B functions
There are very few compounds known containing the CSi2B2 grouping but two such compoundshave been prepared using addition reactions to unsaturated boranes. Thus reaction of methyli-deneborane 32 with the three-membered species 33 gives the five-membered species 34 in 81%yield (Equation (8)) <1995OM1507> and the borataalkyne 35 reacts with Me2SiHCl to give thebicyclo[1.1.1]pentane derivative 36 in 73% yield (Equation (9)) <1995AG(E)657>.
Me B C(SiMe3)2B B
NBut
ButBut B C
BN
BButBut
Me SiMe3SiMe3
But
3233
+
34
ð8Þ
B C B mesmes
SiMe3
Me3SiMe3Si C B C
B
SiSiMe3
MeMe
mesmes
35 36
2 Li
+ 2Me2SiHCl–2 LiCl
–Me2SiH2
– –
+ ð9Þ
The boriranylideneboranes 37 react with B2Cl4 to give the unsaturated species 38 (Equation(10)). If the substituent on boron is But rather than the aromatic group, then B4C-containingspecies are produced, see Section 6.13.1.1.1 <2001EJI387>.
(Me3Si)2C C
B BArAr
CMe3Si
Me3SiCl2B
BCl
Ar
ClAr
38,
+ B2Cl4Hexane
–85 °C
37Ar = C6Me4H, 50%Ar = C6Me3H2, 33%
ð10Þ
(iv) Two Ge and two B functions; two Ge, one Si, and one B functions; and two B, one Si,and one Ge functions
As might be expected from the paucity of CSi2Ge2 and CSi2B2 containing species, there appear tohave been no compounds prepared containing the CGe2B2, CGe2SiB, or CB2SiGe functions.Again, there is unlikely to be any good reason why such compounds should not be made.Reactions between appropriately substituted lithiomethanes and halometalloids should readilyafford the required functions.
6.13.1.2 Methanes Bearing Three Metalloid Functions and a Metal Function
6.13.1.2.1 Three similar metalloid functions
(i) Three Si functions
(a) Three Si and one group 1 metal functions. There has been a surge of interest in the preparationand use of trisilyllithiomethane derivatives because of the previous widespread application of(Me3Si)3CLi and (PhMe2Si)3CLi as bulky alkyl group transfer reagents popularized by Eaborn andSmith <2001JCS(D)1541, 2001JCS(D)3397>. The chemistry and structures of compounds contain-ing these bulky groups have been reviewed. Table 2 gives details of how many of the trisilyllithiumlithium reagents available may be prepared. Several general points can be made. There are two main
Functions Containing at Least One Metalloid (Si, Ge, or B) 389
Table 2 Trisilyllithiomethanes from the reactions of trisilylmethane derivatives and various metallating agents
Trisilylmethane derivativea Metallating agent and conditions Trisilyllithiomethane product Yield (%) References
R3CH MeLi, THF/Et2O R3CLi <1999MI813>R3CH BunLi, hexane R3CLi, base-free <1997JOM(536–537)361>R3CCl Li, toluene, 85–90 �C R3CLi, base-free 86 <1997ZAAC(623)1455>(HMe2Si)3CH LDA, THF (HMe2Si)3CLi <1999OM1804>(PriMe2Si)3CH MeLi, THF, 48 h reflux (PriMe2Si)3CLi <1995JOM(489)181>(Ph2PCH2Me2Si)3CH MeLi 41 66 <2000JCS(D)2183>(Ph2PMe2Si)3CH BuLi, hexane, TMEDA [Li(TMEDA)2][(Ph2PMe2Si)3C] 65 <1999JCS(D)831>(Me2NMe2Si)3CH MeLi, THF [(Me2NMe2Si)2CLi]1 <1996CC741>(o-MeC6H4Me2Si)3CH BuLi, petroleum, TMEDA [Li(TMEDA)2][(o-MeC6H4Me2Si)3CLi] 84 <1997OM6035>[(EtO)3Si]3CH ButLi, THF, –65 �C [(EtO)3Si]3CLi <1998JOM(562)79>R2(CyMe2Si)CH MeLi, THF R2(CyMe2Si)CLi�THF 92 <2001MI(162)225>R2(PhMe2Si)CH MeLi, Et2O R2(PhMe2Si)CLi�Et2O 54 <1997OM4728>R2(PhMe2Si)CH MeLi, THF/TMEDA R2(PhMe2Si)CLi�TMEDA 54 <1997OM4728>R2(PhMe2Si)CH MeLi, THF R2(PhMe2Si)CLi�2THF <1997OM4728>R2(PhMe2Si)CH MeLi, petroleum/TMEDA R2(PhMe2Si)CLi�TMEDA <1997OM4728>R2(Ph2MeSi)CH MeLi, THF/Et2O, 4 h reflux, R2(Ph2MeSi)CH <1995BSf517>R2(2-C5H4NMe2Si)CH MeLi, THF 39 67 <2000OM3224>R2(MeOMe2Si)CCl BuLi, THF, �78 �C R2(MeOMe2Si)CLi�2THF <1998OM4322>R(MeOMe2Si)2CH MeLi mixtureb <1999JCS(D)3267>R(MeOMe2Si)2CH LDA R(MeOMe2Si)2CLi 90 <1999JCS(D)3267>R2(BrMe2Si)CBr PhLi, low temp. R2(BrMe2Si)CLi
c <2000CJC1412>R(FMe2Si)(Bu
t3Si)CBr 2 PhLi R(PhMe2Si)(Bu
t3Si)CLi <1997JOM(531)47>
R(TfOMe2Si)(But3Si)CBr 2 BunLi R(BuMe2Si)(Bu
t3Si)CLi <1997JOM(531)47>
R2(Ph2PMe2Si)CH MeLi R2(Ph2PMe2Si)CLi�2THF 75 <2000JCS(D)2183>R2(Ph2PCH2Me2Si)CH MeLi 42 ca. 90 <2000JCS(D)2183>R2(Me2NMe2Si)CCl BuLi, THF, –78 �C 40 87 <1999OM45>R2(Me2NMe2Si)CH MeLi, THF 40 59 <1999OM45>R(Me2NMe2Si)2CH BuLi R(Me2NMe2Si)2CLi 53 <1999JCS(D)3267>[(Me3Si)2CHSiMe2]2O MeLi, THF 43 90 <1998CC1277>[HCR2SiMe2CH2]2 MeLi, THF/TMEDA [Li(TMEDA)2]
+ salt of 44 79 <1996OM1651>[HCR2SiMe2CH2]2 MeLi, THF [Li(THF)4]
+ salt of 44 43 <1996OM1651>
a R=Me3Si.b Reaction occurs at both the methine C�H and at Si�OMe bonds. c This lithium species eliminates LiBr at room temperature to give the silene (Me3Si)2C¼SiMe2, see text for other related
examples.
synthetic routes,metallation of an Si3C�Hsubstituted carbon, usually byMeLi or BuLi, and treatmentof an Si3C�X (X=Cl or Br) substituted carbon with lithiummetal. The first method is more commonas it is often easier to make the Si3C�H grouping compared to the corresponding Si3C�X andcomplications arising from the incorporation of LiX into reactions following the preparation of thetrisilylmethyllithium reagent are avoided. The yields given in Table 2 are for lithium reagents isolated assolids and fully characterized. The yield of those species without an entry in the yield column can bedetermined indirectly from the yields of derivatives from subsequent reactions. There has been interestin recent years in the preparation of ‘‘base-free’’ trisilylmethyllithium reagents, i.e., not containingcoordinated solvent such as THF or Et2O that can either react or be incorporated into products infurther reactions. Such syntheses are carried out in alkane or aromatic solvents and the reagent formedusually contains no solvent, the lithium atoms being coordinated by alkyl or aryl groups within thetrisilylmethyl substituent. Another extension to this area has been the preparation of reagents contain-ing one or more potentially reactive or coordinating groups within the trisilylmethyl group. Thus,groups such as (RMe2Si)(Me3Si)2C, where R=OMe, NMe2, 2-pyridyl, or PPh2, can be transferred viatheir lithium derivatives to a range of transitionmetal centers where intramolecular coordination by thegroup R promotes monomer formation and discourages formation of oligomeric species. This synthe-tically useful range of reagents will no doubt be expanded in the future to include other morecomplicated ligating groups. A recent example, (Me3Si)2(HMe2Si)CLi(THF)2, containing a reactiveSi�H group can be prepared by treating (Me3Si)2(HMe2Si)CH with MeLi <2004JOM(689)1238>.
The various methods for the preparation of TsiLi, the most popular of the trisilyllithiumreagents, have been described in <1995COFGT(6)377>, but some new variations are includedin Table 2. Sublimation of TsiLi�2THF gives a small amount of TsiLi�1.5THF while reaction ofbase-free TsiLi with O2 in toluene gives (Me3Si)2C¼O, which forms a 1:1 adduct with TsiLi togive TsiLi�O¼C(SiMe3)2 <2000ZAAC(626)2040>. Solid-state 7Li NMR studies of base-freeTsiLi and some of its adducts have also been carried out in order to investigate further therange of structures adopted by this useful reagent <2000JA9858>.
The presence of coordinating groups in the trisilylmethyl substituent leads to species in whichintramolecular coordination occurs to give monomeric species such as 39–41 (see Table 2 for details ofthe syntheses) in which some or all of the coordinating solvent is excluded. Despite the wide variety ofstructures that have found to be adopted by these species in the solid state, they all act as simpletrisilylmethyl derivative transfer agents in solution. The use of these reagents in the synthesis oftrisilylmetallamethane derivatives is detailed extensively in following sections. If two readily metal-lated carbons are present in a molecule, then a double metallation can occur as shown by compounds42–44. Compound 43 is a molecular species containing an unusual interaction between the relativelylow-basicity siloxane oxygen and a lithium, and the [Li(TMEDA)2]
+ salt of anion 44 can be used tomake a range of divalent organometallic complexes as detailed in the following sections.
Me2Si CLi
CMe2SiO(THF)2Li
SiMe3SiMe3
SiMe3
SiMe3
SiC
LiPPh2
Me3SiMe3Si
Li(THF)2
THF
Me2
LiC
Ph2P
Me2Si
Ph2P
SiMe2
Ph2P
SiMe2
C Li
NMe2SiMe3Si
Me3Si THF
SiMe2Me2Si(Me3Si)2C C(SiMe3)2
Li
C Li(THF)2
NMe2
Me3SiMe3Si
Me2Si
39 40 41
42 43 44
Although few examples of polycyclic trisilyllithiomethanes have been reported recently (com-pared to the many described in <1995COFGT(6)377>), the bicyclic species 3 can be monome-tallated, then derivatized and then metallated at the second methine center and further derivatizedas shown in Scheme 1 above. A further series of trisilyllithiomethanes that have receiveddetailed study are of the general form (XR2Si)CLi(SiMe3)2 where R is an alkyl or aryl groupand X is an electronegative function such as halide or alkoxide. As might be expected, thesecompounds need to be prepared at low temperature as they readily eliminate LiX (at differenttemperatures depending on the nature of X) to give silenes R2Si¼C(SiMe3)2. For example,
Functions Containing at Least One Metalloid (Si, Ge, or B) 391
reaction between (XPh2Si)(Me3Si)2CBr (X=F or Br) with BuLi or PhLi at �78 �C in Et2O gives(XPh2Si)(Me3Si)2CLi, which then generate Ph2Si¼C(SiMe3)2 <1995CB1231, 1995CB1241> and(XMe2Si)(Me3Si)2CBr (X=alkoxide or halide) react with BuLi or PhLi at low temperature togive (XMe2Si)(Me3Si)2Cli, which can then be used to generate Me2Si¼C(SiMe3)2<2000CJC1412, 2000JOM(598)292, 2000JOM(598)304>.
Trisilyllithiomethane derivatives sometimes result unexpectedly from complicated reactions andrearrangements, the relative stability of trisilylmethyl anions perhaps being a driving force for this.For example, (Me3Si)2(HMe2Si)CLi is found to be an intermediate in the reaction between MeLi andMe3SiSiMe3 <2000OM374>, and the disilylmethane derivative (MeOMe2Si)2CH2 reacts with ButLiin pentane at �78 �C to give (MeOMe2Si)2CHLi, which undergoes a remarkable skeletal rearrange-ment to give the previously prepared dimer 45 (intra- and intermolecular coordination of Li in[{LiC(SiMe2OMe)3}2]; methyl groups have been omitted for clarity) in 64% yield <2003OM2505>.
LiO Si
C
Si O
C
LiOSi
O Si
O
Si
Si
O
45
The popular synthetic use of trisilylmethyllithium derivatives, particularly in transition metalchemistry, has prompted the synthesis of similar species incorporating heavier group 1metals. Clearly,such compounds are likely to be more difficult to prepare being intolerant of ether solvents, and willbe more difficult to handle because of their sensitivity toward water and oxygen. Despite theseproblems there are now well-characterized sodium, potassium, rubidium, and caesium derivatives oftrisilylmethanes, some of which have been shown to be synthetically useful. Sodium derivatives can beprepared in a similar way to some of their lithium analogs, for example, (PhMe2Si)(Me3Si)2CH reactswith MeNa in petroleum containing TMEDA to give (PhMe2Si)(Me3Si)2CNa�TMEDA in 34% yield<1997OM4728>. Alkali metal exchange may also be a useful synthetic route in preparing sodiumcompounds; thus, reaction of (Ph2PMe2Si)(Me3Si)2CLi�2THF reacts with ButONa to give (Ph2PMe2-Si)(Me3Si)2CNa in which the sodium is coordinated to both the carbanionic center and to a phenylgroup <2000JCS(D)2183>. In the search for stable silenes, even more bulky trisilylmethane deriva-tives have been prepared, e.g., treatment of (FMe2Si)(Bu
t3Si)(Me3Si)CBr with But3SiNa affords
(FMe2Si)(But3Si)(Me3Si)CNa, which can then potentially eliminate NaF <1997JOM(531)47>.
Trisilylmethylpotassium derivatives can be prepared in a similar manner to the analogouslithium compounds. Thus, reaction of TsiH with MeK in Et2O in the presence of TMEDA givesTsiK�TMEDA in 34% yield, (Me3Si)2(PhMe2Si)CH reacts with MeK in Et2O at �20 �C to give(Me3Si)2(PhMe2Si)CK in 60% yield <1997OM4728>, and (MeOMe2Si)2(Me3Si)CH reacts withMeK to give (MeOMe2Si)2(Me3Si)CK cleanly <1999JCS(D)3267>. If (Me3Si)2(PhMe2Si)CK iscrystallized from benzene, orange crystals of the potassate [K(C6H6)][K{C(SiMe3)2(SiPhMe2)}2]may be isolated <1995AG(E)2679>. The reactivity of the potassium compounds can be shownfrom the reaction of the vinyl derivative, (Me3Si)2(CH2¼CHMe2Si)CK (prepared from(Me3Si)2(CH2¼CHMe2Si)CH and MeK) with adventitious silicone grease in its container over aperiod of 4 weeks to give [K(SiMe2O)7][K{C(SiMe3)2(SiMe2CH2¼CH)}2] <1995AG(E)2679>.Alkali-metal exchange may also be useful as a synthetic route, species 39 reacts with ButOK togive the potassium analog (2-C5H4NMe2Si)(Me3Si)2CK which contains no solvent, the potassiumbeing coordinated as shown in 46 in a polymeric structure <2000OM3224>.
C K
NMe2Si
Me3Si SiMe3
C K
NMe2Si
Me3Si SiMe3
46
392 Functions Containing at Least One Metalloid (Si, Ge, or B)
The [Li(THF)4]+ salt of 44 can also be used in the preparation of the dipotassium species 47, or a
benzene solvate of the same species, 48 can be prepared directly from 49 as shown in Scheme 3<1999OM2342>. The dicaesium compound 50 can be prepared in a similar manner<2000OM1190>.
Rare examples of structurally characterized alkylrubidium and caesium derivatives can be madeusing the reaction between MeM (M=Rb or Cs), prepared in situ from MeLi and the corre-sponding alkali-metal-2-ethylhexoxide, and TsiH. Thus, TsiRb is prepared in 64% yield andcomprises an infinite chain of alternating planar Tsi� anions and Rb+ cations, and TsiCscrystallizes from benzene to give TsiCs�3.5C6H6 in which the Cs is coordinated to both thecarbanion center and three benzene molecules <1995AG(E)687>. Similar reactions but using(PhMe2Si)3CH as starting material give (PhMe2Si)3CRb and (PhMe2Si)3CCs in yields of 74 and66%, respectively <1997OM4728>. The structure of the rubidium species shows that the rubi-dium is coordinated by the aromatic groups of the trisilylmethyl substituent.
The uses of these Na, K, Rb, and Cs derivatives of trisilylmethanes are largely unexplored butthe widespread use of the Li analogs suggests that they may well have significant potential,particularly in organometallic chemistry.
(b) Three Si and one group 2 metal functions. The reaction of (Me2NMe2Si)3CI with Mg in Et2Ogives (Me2NMe2Si)3CMgI in 54% yield. Although it has the general Grignard reagent formula ofRMgX, a structural study has shown that the central carbanionic carbon has a planar environment andthat there is in fact no significant C�Mg interaction, the coordination sphere of the Mg comprisingthree nitrogen and one iodide ligand<1997OM503>. The reaction of (MeOMe2Si)(Me3Si)2CI withMgin Et2O is thought to give the Grignard reagent (MeOMe2Si)(Me3Si)2CMgI, which decomposes to givethe dialkylmagnesium species Mg{C(SiMe3)2(SiMe2OMe)}2 in 50% yield together with MgI2�(OEt2)2.The Grignard compound can however be isolated in 80% yield from the reaction between (MeOMe2-Si)(Me3Si)2CI andMg in toluene solution<1996JOM(521)113>. A variety of other more complicatedorganomagnesium complexes containing solvent are also available from similar preparative routes.Thus, reaction of reagent 39 (see Section 6.13.1.2.1 above) with MgBr2 gives 51 <2000OM3224> butwith [MgBr2(OEt2)2] the Li is retained to give complex 52 <2001JOM(631)76>. The ate complex,[Li(TMEDA)2][Li{C(SiMe3)2(SiMe2Ph)}2], reacts with MgBr2 in THF solution to give 53 in poor yield<2001JOM(631)76>. Grignard reagents 54 are formed when R3CI species (R=Me3Si or PhMe2Si)react with activated magnesium and an unusual, unsymmetrical dialkylmagnesium compound, 55, isobtained in 95% yield from the reaction between [MgBr2(OEt2)2] and the lithium reagent formed fromBuLi and (Me2NMe2Si)(Me3Si)2CI in Et2O with <2001JOM(631)76>.
C MgNMe2Si
Me3SiMe3Si
THFBr
C Mg
Me2Si
Me3SiMe3Si
OEt2Bu
NMe2
C MgNMe2Si
Me3SiMe3Si
BrBr Li(THF)3
MgBr
LiBr
NMe2
Me2N
(PhMe2Si)(Me3Si)2C
THF
MgI
MgI OEt2
CR3Et2O
R3C
54, R = Me3Si or PhMe2Si 55
5352
51
CH2Me2Si(Me3Si)2CHCH2Me2Si(Me3Si)2CH
[Li(THF)4] 44
CH2Me2Si(Me3Si)2CK(THF)2
CH2Me2Si(Me3Si)2CK(THF)2
CH2Me2Si(Me3Si)2CK(C6H6)CH2Me2Si(Me3Si)2CK(C6H6)
CH2Me2Si(Me3Si)2CCs(C6H6)CH2Me2Si(Me3Si)2CCs(C6H6)
MeLi, THF
ButOK,
THFMeK,C6H6
47 48
49
50
ii. Cryst. from C6H6
i. MeCs, Et2O
Scheme 3
Functions Containing at Least One Metalloid (Si, Ge, or B) 393
The steric protection afforded by the Tsi group is seen clearly in the isolation of Tsi2Ca, thefirst solvent-free dialkylcalcium compound to be structurally characterized and which is obtainedfrom the reaction between 2 equiv. of TsiK and 1 equiv. of CaI2 in 87% yield <1997CC1961>.Use of a bulky trisilyllithium reagent containing a group capable of intramolecular coordinationallows the preparation of simple, monomeric dialkyl derivatives of strontium and barium. Thus,reaction of 2 equiv. of (MeOMe2Si)(Me3Si)2CK with MI2 (M=Sr or Ba) in THF affords[(MeOMe2Si)(Me3Si)2C]2M(THF)n, which when crystallized from methylcyclohexane, for M=Sr,gives [(MeOMe2Si)(Me3Si)2C]2Sr(THF) in 72% yield, and when crystallized from (Me2SiO)3/DME,for M=Ba, gives [(MeOMe2Si)(Me3Si)2C]2Ba(DME) in 68% yield <2003JA7534>.
(c) Three Si and one group 12 metal functions. Reaction between TsiLi and ZnCl2 affordsTsiZnCl in 26% yield as an isolated product after sublimation of the initially formed [Li(THF)4][(TsiZn)2Cl3] <1998EJI1175, 1999JOM(572)249>. This is presumably also an intermediate in thesequential treatment of ZnCl2 with TsiLi followed by LiP(SiMe3)2 to give TsiZnP(SiMe3)2 in 60%yield <1995ZAAC(621)287>. Reaction of the trisilyllithiomethane derivative 39 containing a poten-tially chelating group with ZnBr2 or CdCl2 gives the halide-bridged dimers 56 and 57 in 67% and 69%yields respectively <2002JCS(D)2467> and reaction of reagent 40 with ZnBr2 affords an analogouscyclic dimer<2004JOM(689)1718>. The monomeric species 58M=Zn is formed in 60% yield fromthe reaction of the [Li(TMEDA)2] salt of the diorganolithiate ion 44 with ZnCl2 <1999OM2342>.
A series of crowded diorganomercury compounds have been prepared by metathesis reactions.Thus, TsiHgR compounds can be prepared by reaction of TsiHgBr with RMgX (R=Me, Pri, Bun,But, or Ph) and (PhMe2Si)3CHgR compounds from (PhMe2Si)3CHgCl and RLi (R=Me, Pri, Bun,But, or Ph). Treatment of (PhMe2Si)3CHgCl with TsiLi gives the extremely bulky (PhMe2Si)3CHgTsiin 21% yield. The symmetrical dialkylmercury derivative [(Me3Si)2(HMe2Si)C]2Hg is obtained in 16%yield from the reaction between HgCl2 and (Me3Si)2(HMe2Si)CLi at �110 �C <1996JOM(510)143>.Other congested organomercury compounds containing potentially chelating groups can also beprepared by simple metathesis reactions. Thus, reaction between (MeOMe2Si)2Me3SiCK and HgBr2gives (MeOMe2Si)2Me3SiCHgBr in 31% yield <1999JCS(D)3267>, reaction of 40 with HgBr2 gives[(Me2NMe2Si)(Me3Si)2C]2Hg in 51% yield<1999OM45>, reaction of 39with HgCl2 gives 59 in 62%yield <2002JCS(D)2467>, and reaction of the [Li(TMEDA)2] salt of the diorganolithiate ion 44 withHgBr2 gives a 91% yield of 60 <1996OM1651>.
C MNMe2Si
Me3SiMe3Si X
XMN
CSiMe2
SiMe3
SiMe3
C HgNMe2Si
Me3SiMe3Si Cl
SiMe2Me2Si(Me3Si)2C C(SiMe3)2
M
56, M = Zn, X = Br57, M = Cd, X = Cl
58, M = Zn60, M = Hg 59
(d) Three Si and one group 13 metal functions. There has been increasing interest in compoundscontaining a Si3MC grouping (where M=Al, Ga, In, or Tl) and several such compounds havebeen found to be useful precursors to a wide range of novel organometallic compounds. Thesynthesis of these compounds relies largely on metathesis reactions between a bulky trisilyllithiumreagent [for their synthesis see Section 6.13.1.2.1.(i).(a)] and a metal halide. One potential problemwith this synthetic method is that coordinating solvents, such as THF or Et2O that are convenientto use in the synthesis of the organolithium reagent, may be cleaved by strong Lewis acidic group13 compounds. For example, the reaction of TsiLi with BX3 (X=F, Cl, or Br) in Et2O affordsTsiOEt and not TsiBX2 species <1995OM3098>. This problem can be avoided by the use ofbase-free trisilyllithium reagents [for their synthesis see Section 6.13.1.2.1.(i).(a)].
The reactions between bulky trisilyllithium reagents and aluminum halides give the productsexpected from metathesis reactions. For example, TsiAlMe2�THF is formed in 85% yield fromthe reaction between TsiLi�2THF and Me2AlCl in THF <1997CEJ1783> and the solvent-free TsiAlMe2 is formed in 68% yield when base-free TsiLi in toluene is used<1997ZAAC(623)1455>. Similarly, reaction of (CyMe2Si)(Me3Si)2CLi�THF (Cy=cyclohexyl)with Me2AlCl gives (CyMe2Si)(Me3Si)2CAlMe2�THF in 88% yield and which has been used to
394 Functions Containing at Least One Metalloid (Si, Ge, or B)
prepare a range of other (CyMe2Si)(Me3Si)2CAlX2 derivatives <2001MI(162)225>. The dimethylderivative TsiAlMe2�THF is also a useful precursor to other crowded alanes. For example, thereaction with Me3SnX (X=F or Cl) gives TsiAlX2�THF, and with Br2 or I2 gives TsiAlBr2�THFand TsiAlI2�THF, respectively <1998OM2249>. Reduction of TsiAlI2�THF by NaK alloy givesthe tetrahedrane [TsiAl]4, analogous to the tetrahedranes of Ga, In, and Tl described below<1998AG(E)1952>. Base-free TsiLi reacts with AlCl3 at �78 �C in a 1:1 ratio to give Li[TsiAlCl3]in 83% yield <1997ZAAC(623)1455> but if 2 equiv. of TsiLi are used then a methylation occursto give TsiAlMeCl <2001ZAAC(627)715>. If a coordinating group is present in the trisilyllithiumreagent or the aluminum halide, then solvent may be excluded from the coordination sphere ofthe aluminum in the product. For example, reaction of 40 with AlCl3 generates 61 in 91% yield<1999OM45>, reaction of (Me2NMe2Si)3CLi with AlCl3 in toluene containing THF gives 62 as acolorless solid in almost quantitative yield <1998OM3135>, and the product, 63, in Equation(11) is formed in 50% yield in THF solution <1995CB493>. However, the weaker basic OMe sitein 64, derived from the reaction of (Me3Si)2(MeOMe2Si)CLi�2THF with AlCl3 in 62% yield, doesnot prevent THF from coordinating to the Al <1998OM4322>.
C AlNMe2
Me3SiMe3Si Cl
ClMe2Si
C
Me2SiAlCl2
NMe2Me2NMe2SiMe2NMe2Si
C AlMe3Si
Me3Si
MeOMe2Si
Cl
ClTHF
61 62 64
AlCl2
NMe2Al
NMe2
C(SiMe3)3Cl
(Me3Si)3CLi +THF, –78 °C
63
ð11Þ
Bulky trisilyllithium reagents have also been used to prepare sterically hindered aluminumhydrides, which are often monomeric in contrast to species containing less sterically demandingsubstituents. For example, the treatment of TsiLi with H3Al�NMe3 readily affords TsiAlH2�THF in86% yield <2001OM2047>. Several trisilyllithium reagents, (RMe2Si)(Me3Si)2CLi (where R=Me,Ph, or NMe2), react with LiAlH4 in THF to give cyclic dimers 65 <1994OM4143,2000JOM(597)3>. These structures all incorporate THF, excluding, in the case where R=NMe2,coordination of aluminum by the nitrogen. Treatment of the dimers where R=Me or Ph withMe3SiCl gives the simple hydrides (RMe2Si)(Me3Si)2CAlH2�THF in 40% and 50% yields, respec-tively <2000JOM(597)3>. Reaction of 65, where R=Me, with 4 equiv. of 2,6-Pri2C6H3OH givesthe diaryloxo species 66 in 75% yield and with Ph3SiOH the monomeric 67 is formed in 98% yield<2002JCS(D)3971>. The trisilyllithium reagent (MeOMe2Si)(Me3Si)2CLi�2THF reacts withLiAlH4 in THF to give 68 in which the weakly basic SiOMe group does coordinate to the Li toexclude coordination by a second THF molecule <1998OM4322>. (The structure of 68 was laterfound to be dimeric <2000JOM(597)3>.) The reaction of (MeOMe2Si)2(Me3Si)CLi with LiAlH4
gives [Li(THF)4][(MeOMe2Si)2(Me3Si)CAlH3] <1999JCS(D)3267>.
C AlH2
H
LiMe2Si O
Me3Si
Me3Si
THF
Li HAl
HLi
HAl
H
H(RMe2Si)(Me3Si)2C
H C(SiMe3)2(SiMe2R)
(THF)2
(THF)2
OLi
AlO
H Tsi
R
R
R
R
THF
(Me3Si)3C AlOSiPh3
OSiPh3
THF Me
R = Me, 64%R = Ph, 56%R = NMe2, 95%
R = Pri
6566
67 68
Functions Containing at Least One Metalloid (Si, Ge, or B) 395
Some remarkable polymetallic compounds have been isolated from the reaction between TsiLi andthe gallium(I) halide GaBr. Thus, the reaction in toluene/THF at�78 �C affords the lithium salt of theanion [Ga19Tsi6]
� in 30% yield <2000JA9178> and a small amount of the fused tetrahedranederivative 69 <2001AG(E)1241>. The [Ga19Tsi6]
� anion contains a central Ga13 metal core sur-rounded by six Tsi–Ga substituents. Use of the simpler, related tetrahedrane [TsiGa]4, as a source ofthe monomer TsiGa for the preparation of a wide variety of organometallic compounds containingTsiGa as a ligand has been demonstrated (see, e.g., <2001IC750, 2000JCS(D)3133>).
Ga
GaGaGa Ga
GaGa
Ga
C(SiMe3)3
C(SiMe3)3
C(SiMe3)3C(SiMe3)3
(Me3Si)3C
C(SiMe3)3
In Br In
Br
InC(SiMe3)3(Me3Si)3C
(Me3Si)3C BrLi(THF)3
7169
The reaction of base-free TsiLi and GaX3 (X=Cl or I) at �78 �C in a 1:1 ratio givesLi[TsiGaX3], but if 2 equiv. of TsiLi are used then a methylation occurs to give TsiGaMeCl<2001ZAAC(627)715>. Reaction of GaCl3 with (EtMe2Si)3CLi gives [Li(THF)4][(EtMe2Si)3-CGaCl3] in 49% yield. Both this species and the (Me3Si)3C analog can be reduced by magnesiumto give the corresponding tetragallium tetrahedranes <1998JOM(555)263>. The THF adduct,TsiGaMe2�THF, can be isolated in 90% yield from the reaction between TsiLi�2THF andMe2GaCl in THF. When the adduct is sublimed the THF is lost to give the solvent-freeTsiGaMe2 <1997CEJ1783>, which can also be prepared in 58% yield from the reaction betweenbase-free TsiLi and Me2GaCl <1997ZAAC(623)1455>. If a coordinating group is present in thetrisilyllithium substituent, then solvent is excluded from the product; thus, reaction of 40 withGaCl3 generates the gallium analog of 61 in 58% yield <1999OM45>.
The reactions between InBr and trisilyllithium reagents as shown in Equation (12) affordoligomers of (RR1MeSi)3CIn, 70 <1995JOM(493)C1, 1998OM5009>. For RR1=Me2, EtMe,and BunMe the compounds are tetrameric in benzene solution, while for the larger cases ofRR1=MePri and MePh the compounds are monomers in solution. For RR1=Et2 there is amonomer–dimer equilibrium in solution. In the solid state when RR1=Me2, EtMe, Et2, orMePri, the compounds are tetrameric, having a near perfect tetrahedral arrangement of indiumatoms, similar to the tetrahedral gallium species described previously <1995COFGT(6)377>. Inthe reaction of TsiLi with InBr an unusual species 71 is also formed in 24% yield, which containsa chain of three indium atoms <2002ZAAC(628)1963>. The tetrahedrane [TsiIn]4 has been usedas a convenient source of the monomer TsiIn for the preparation of a variety of organometalliccompounds containing TsiIn (see, e.g., <2003OM2705, 2001CEJ4216, 2001IC750,2000ZAAC(626)2043>).
InBr + (RR1MeSi)3C-LiToluene, –40 °C
[(RR1MeSi)3CIn]n
70 R = Me, R1 = Me, 69%; R = Me, R1
= Et, 47%R = Me, R1
= Bun, 57%; R = Me, R1 = Pri, 64%
R = Me, R1 = Ph, 66%; R = Et, R1
= Et, 56%
ð12Þ
The reaction of In(III) compounds with bulky lithium reagents has also continued to be of interest.Thus, the reaction of InBr3 with TsiLi in THF/Et2O gives a 60% yield of [Li(THF)4][TsiInBr3]<1998ZAAC(624)4> and the reaction of TsiLi with Me2InCl in Et2O gives TsiInMe2 in 65% yield<1997ZAAC(623)1455>. The reaction of base-free TsiLi and InX3 (X=Cl, Br, or I) at �78 �C in a1:1 ratio gives Li[TsiInX3] but if 2 equiv. of TsiLi are used then a methylation occurs to giveTsiInMeCl, and if 3 equiv. of TsiLi are used then two methylations occur to give TsiInMe2 togetherwith the 1,3-disilacyclobutane [Me2Si�C(SiMe3)2]2 <2001ZAAC(627)715>. If moisture is present inthe reaction between TsiLi and Prn2InBr, an unusual hydroxide-bridged trimer, 72, is formed in 28%yield, presumably via hydrolysis of the initially formed TsiInPr2
n <1999ZAAC(625)547>.Some of the chemistry described above for gallium and indium can be extended to thallium. The
reaction of TsiLi with the thallium(I) organometallic TlCp in a 1:1 ratio gives the deep red-violetTsiTl, which is tetrameric in the solid state having a slightly distorted tetrahedron of thallium atomssimilar to that described above for the gallium and indium analogs <1997AG(E)64>.
396 Functions Containing at Least One Metalloid (Si, Ge, or B)
In
HO
In
HOIn
OH
C(SiMe3)3
Prn
(Me3Si)3C
Prn(Me3Si)3C
Prn
72
(e) Three Si and one group 14 metal functions. Compounds containing the Si3MC groupingwhere M=Sn or Pb are usually made by simple metathesis reactions between trisilyllithiumreagents and metal halides. For example, reaction between SnX4 and TsiLi in Et2O at �78 �Caffords the expected TsiSnX3 compounds in excellent yields, 91% for X=Cl <2002AG(E)1365>and 89% for X=Br <1999EJI869>. However, reaction between (Me3Si)3CLi and SnX4 (whereX=Cl, Br, or I) in a 2:1 ratio in toluene solution gives (Me3Si)3C(PhCH2)SnX2 in 58%, 72%,and 76% yields respectively for X=Cl, Br, or I, apparently via a radical mechanism similar tothat found in the germanium analog described in Section 6.13.1.1.2 <1999ZAAC(625)1807>. Therelated bulky reagent, (PhMe2Si)3CLi, reacts with SnCl4 in THF to give only a 25% yield of(PhMe2Si)3CSnCl3 along with (PhMe2Si)3CCl as the main product but it reacts more cleanly withMe2SnCl2 to give (PhMe2Si)3CSnMe2Cl, which reacts readily with EtOH to give the final product(PhMe2Si)3CSnMe2OEt in 76% yield <1998JOM(564)215>. Related reagents that containsubstituents capable of intramolecular coordination to the tin atom also undergo similarmetathesis reactions. Thus reaction of 40 with SnCl4 gives (Me2NMe2Si)(Me3Si)2CSnCl3,which probably has intramolecular Sn�N coordination, in 78% yield <1999OM45>, andtreatment of (Me2NMe2Si)2(Me3Si)CLi with Me3SnCl gives (Me2NMe2Si)2(Me3Si)CSnMe3(along with the precursor (Me2NMe2Si)2(Me3Si)CH) <1999JCS(D)3267>. Derivatizationusing Bu3SnCl of the organometallic reagent formed by metallation of 3 affords a derivativeof 5 in which a Bu3Sn group has replaced the SiMe2R group <1998CL1145>. It is likely thata second metallation and further reaction with a tin halide would give a further range ofcompounds containing two Si3SnC substituted centers. Introduction of two tin atoms occursin the reaction of the [Li(TMEDA)2] salt of 44 with Me2SnCl2 or the [Li(THF)4] salt of 44with SnCl4 to afford [ClR2SnC(SiMe3)2SiMe2CH2]2 in 79% and 47% yields, respectively forR=Me and Cl <1999OM2342>.
The Si3SnC grouping has also been prepared by using the reaction between a disilylstannyl-lithium reagent and a silyl chloride. Thus, (Me3Si)2(PhMe2Sn)CLi reacts with Me2SiCl2 to furnish(Me3Si)2(PhMe2Sn)CSiMe2Cl in 76% yield <1998JOM(564)215>. Reactions of (Me3Si)2(Ph-Me2Sn)CLi (for its synthesis, see Section 6.13.1.3.1) with a range of other metal halides would,no doubt, allow convenient preparation of many new Si2SnMC groupings.
The high degree of steric protection afforded by an (R3Si)3C substituent at a group 14 metalcenter has prompted investigation into the stabilization of M(II) species where M=Sn or Pbby such substituents. Reaction of (Me3Si)2(2-NC5H4Me2Si)CLi with SnCl2 or PbCl2 givesmonomeric organotin- and organolead(II) chlorides in 74% and 47% yields, respectively,which have structures analogous to that of the related germanium compound 27<2001OM1223>. The bis-methoxy species (MeOMe2Si)2Me3SiCLi reacts with SnCl2 to give(MeOMe2Si)2Me3SiCSnCl in 65% yield <1999JCS(D)3267>. The first structurally character-ized organometallic ate complex of Sn(II), has a structure similar to that of the germaniumanalog, 28, and has been prepared in 60% yield from the reaction of (Me3Si)3CLi withSn(SBun)2 <2002OM4005>. Treatment of the K(THF)2 salt of [CH2(SiMe2)(Me3Si)2C]
2�2
(see Section 6.13.1.2.1(a)) with SnCl2 in Et2O at �78 �C gives a mixture of dialkyl Sn(II)compounds 73 (M=Sn) and 74, both of which readily undergo oxidative addition reactionsto give Sn(IV) compounds <1997OM5621, 2000OM49, 2002OM2183, 2002OM2430>. Chloro-bridged dimers 75 are formed from the reaction of (PhMe2Si)3CLi and MCl2 in THF<1995CC1829, 1997OM5653>. The lead species is a yellow-orange solid and is the firstmonoorganolead(II) derivative to be characterized. In contrast, if the smaller reagent TsiLireacts with PbCl2 in THF then a chloro-bridged trimer 76 is produced in 85% yield<1997OM5653>. When the organolithium reagent (MeOMe2Si)(Me3Si)2CLi reacts withMCl2, where M=Sn or Pb, intramolecular coordination of the OMe group to the metaloccurs to give the four-coordinate M(II) species 77 <1997OM5653>. Treatment of the[Li(TMEDA)2] salt of 44 with PbCl2 gives the Pb(II) organometallic species 73 (M=Pb) asdark blue crystals in 85% yield <1997OM5621>.
Functions Containing at Least One Metalloid (Si, Ge, or B) 397
MClCl
M(PhMe2Si)3C
C(SiMe2Ph)3SiMe2Me2Si(Me3Si)2C C(SiMe3)2
M
CH2Me2Si(Me3Si)2CSnClCH2Me2Si(Me3Si)2CSnCl
PbCl
PbClPb
Cl C(SiMe3)3
C(SiMe3)3
(Me3Si)3CM SiMe2
Cl
Cl
O
CCO
MMe2Si
Me
Me
SiMe3
SiMe3Me3Si
Me3Si
73, M = Sn or Pb 75, M = Sn or Pb
77, M = Sn, 93%; M = Pb, 60%
74
76
(f) Three Si and one transition metal functions. The reaction of lithium reagent 39 with CrCl2gives a 40% yield of 78 having a square-planar geometry at Cr, together with a small amount of79 <2000OM3224>. Reaction of TsiLi�2THF with CrCl2 is reported to give Tsi2Cr, but no detailshave been given <2002USP00334829>.
C CrNMe2Si
Me3SiMe3Si Cl
ClCrN
CSiMe2
SiMe3
SiMe3C CrNMe2Si
Me3SiMe3Si
CN
SiMe3
SiMe3
SiMe2
78 79
Reaction of the lithium reagent 39 with MnCl2 gives the manganese complex 80 in 41% yield<2000OM3224>. Similarly, the lithium reagent 40 reacts with 1 equiv. of MnCl2 to give a 95%yield of 81 X=Cl, and with 0.5 equiv. of MnCl2 to give [(Me2NMe2Si)(Me3Si)2C]2Mn in 72%yield together with a small amount of the Mn(III) complex 81 X=O (presumably formed viaoxidation by adventitious air) <2002JOM(649)121>. Reaction of the related reagent containing achelating methoxy group (see Table 2) with MnCl2 gives 82 in 63% yield <2002JOM(649)121>while the use of the chelated dialkyllithium reagent 44 affords the chloride-bridged, high-spinmanganese complex 83 in 60% yield <2000OM1190>.
C MnNMe2Si
Me3SiMe3Si Cl
Cl Li(THF)3
C MnNMe2
Me3SiMe3Si X
XMn
Me2N
C SiMe3
SiMe3
Me2Si
SiMe2
CMe2Si
OMe
MnCl
MnCl
C(SiMe3)2
SiMe2
MeO
THF
THF(Me3Si)2
SiMe2Me2Si(Me3Si)2C C(SiMe3)2
Mn
ClLi(THF)3
81, X = Cl, X = O80
82 83
Reaction of base-free TsiLi with FeCl3 leads to reduction and formation of the Fe(II) com-pound Tsi2Fe in 68% yield <2001ZAAC(627)715>. If coordinated THF is present in the lithiumreagent, TsiLi�2THF, then reaction with FeCl2 at �35 �C in THF solution also occurs to give redblocks of Tsi2Fe in 44% yield <2003ICA(345)359, 2002USP00334829>.
398 Functions Containing at Least One Metalloid (Si, Ge, or B)
Reaction of the lithium reagent 39 with CoBr2 gives the halide-bridged ate complex 84 in 56%yield <2000OM3224>. Similarly, lithium reagent 40 containing a dimethylamino substituentcapable of acting as a ligand, reacts with CoBr2 to give 85 in 50% yield <2002JOM(649)121>.The simple diorganocobalt compound Tsi2Co has been reported to be formed as dark-green,plate-like crystals from the reaction between CoCl2 and TsiLi�2THF but no spectroscopic detailsare available <2002USP00334829>.
C CoNMe2Si
Me3SiMe3Si Br
BrLi(THF)2
C CoNMe2
Me3SiMe3Si Br
BrCo
Me2N
C SiMe3
SiMe3
Me2Si
SiMe2
84 85
The first �-bonded organonickel(I) compound 86 is obtained in 30% yield from the reactionshown in Scheme 4. Trace amounts of hydroxide present in the starting material are thought to beresponsible for the formation of complex 87 as a minor by-product. In contrast, reaction of[PdCl2(PPh3)2] gave the chloro-bridged dimer 88 as a pale yellow solid in 53% yield <2000CC691>.
Reaction of 39 with CuI or AuCl�SMe2 gives dimeric products 89 M=Cu or Au in 62% and37% yields, respectively <2002JCS(D)2467>.
(Me3Si)2C
Me2Si
NMN
SiMe2
C(SiMe3)2
M 89, M = Cu or Au
The reactions between group I metal derivatives of trisilylmethanes and CuCN can give avariety of products. Thus, treatment of CuCN with (PhMe2Si)3CM (M=Li or Na) in THFsolution affords the monomeric species (PhMe2Si)3CCuCNM(THF)3 which, when crystallizedfrom toluene, gives the dimeric species 90 <2000OM5780>. Similar dimers, 91 and 92, areformed, in 65% and 41% yield, respectively, directly from reactions with (RMe2Si)(Me3Si)2CLi(R=Me or NMe2) while (MeOMe2Si)2(Me3Si)CLi gives 93 <2002JCS(D)3975>. Crystallizationof the product formed from the potassium reagent (PhMe2Si)3CK and CuCN gives the tetramer94 in 43% yield <2000OM5780>.
C LiNMe2Si
Me3SiMe3Si THF [NiCl2(PPh3)2]
C Ni
NMe2SiMe3Si
Me3Si PPh3
NN
Me2Si CNi
SiMe2
ONi
OC
Me2Si
N
SiMe2
SiMe3
Me3Si
PdCl
ClPd
N
SiMe2C
Me2Si C
Me3Si SiMe3
SiMe3Me3Si
[PdCl2(PPh3)2]
2
THF, –78 °C trace H2O
THF, –78 °C
8687
88
Scheme 4
Functions Containing at Least One Metalloid (Si, Ge, or B) 399
LiCN
LiNC CuRRCu
THFTHF
THFTHF
N
N
K
K
K
N
N
K
CCuR
CCuR
CRCu
CRCu
C Cu CN Li
Me2Si
OMe
Li
Me3Si
Me2Si
MeO
CN Cu C
SiMe3
SiMe2SiMe2
MeOOMe
THF
THF
90, R = (PhMe2Si)3C91, R = (Me3Si)3C92, R = (Me2NMe2)(Me3Si)2C
94, R = (PhMe2Si)3C
93
(g) Three Si and one lanthanide or actinide functions. The first structurally characterized�-bonded organosamarium(II) complex [Sm{C(SiMe3)2(SiMe2OMe)}2�THF] was obtained fromthe reaction between K{C(SiMe3)2(SiMe2OMe)} and [SmI2(THF)2]. The compound is isolated asdeep green-black, air-sensitive crystals in 71% yield and should inspire further work into alkyl,rather than the more well-known cyclopentadienyl, derivatives of samarium <1997AG(E)2815>.Reaction of a range of alkylpotassium species with YbI2 (Equation (13)) in benzene solution givessimple, monomeric dialkylytterbium compounds 95 <1994JA12071, 1996OM4783> including thesolvent-free dialkyl lanthanide compound Tsi2Yb as an orange solid in 85% yield which, despite thesteric encumbrance of the Tsi groups, is bent at Yb (C�Yb�C angle 137�) and can act as apolymerization catalyst for methylmethacrylate <2002JOM(647)128, 2003T10409>. A similarmetathetical reaction occurs between TsiK and EuI2 to give the bent species Tsi2Eu in 65% yield<1996OM4783>. Grignard-like complexes [RYbI�Et2O]2, 96, are formed from the reaction betweenRI and elemental Yb in Et2O (Equation (14)) <1994JA12071, 1996OM4783>. Reaction of thedipotassium compound 48 with YbI2 in benzene solution affords 97 in 45% yield <1999OM2342>.In contrast to the reactions carried out in benzene as a solvent, reaction between TsiK and YbI2 inEt2O in either a 2:1 or a 1:1 ratio gives the centrosymmetric dimer 98 as orange-red crystals in 63%yield. It is not clear how the EtO� group is generated, but possibly by the Lewis acid character ofinitially formed Tsi2Yb or TsiK cleaving the solvent <1994CC2691, 1995JCS(D)3933>.
C6H6YbI2 + 2(Me3Si)2(Me2RSi)CK [(Me3Si)2(Me2RSi)C]2Yb + 2KI
95, R = Me, 85% R = CH2=CH, 80% R = EtOCH2CH2, 70%
ð13Þ
Et2OYb
II
YbC(SiMe3)2(SiMe2R)
OEt2
Et2O
(RMe2Si)(Me3Si)2C(Me3Si)2(Me2RSi)CI + Yb powder
96, R = Me R = OMe, 65%
ð14Þ
SiMe2Me2Si(Me3Si)2C C(SiMe3)2
Yb
YbOEt
EtO
YbC(SiMe3)3
OEt2
Et2O
(Me3Si)3C
97 98
No trisilylmethyl derivatives of the actinide elements seem to have been prepared.
400 Functions Containing at Least One Metalloid (Si, Ge, or B)
(ii) Three Ge and one metal functions
As has been seen in sections above there is a general lack of compounds containing severalgermanium atoms attached to the same carbon and there do not appear to be any compoundscontaining the Ge3MC grouping known. Such compounds should be readily available via theroutes used to prepare the many analogous Si3MC containing functions as described above.
(iii) Three B functions
As has been described above, there are few compounds containing several boron atoms attachedto carbon apart from carboranes and other compounds with multicenter bonding. See reference<1995COFGT(6)377> for early work in this field.
6.13.1.2.2 Other mixed metalloid functions
(i) Two Si, one Ge, and one metal functions
Treatment of XMe2GeCBr(SiMe3)2 with PhLi (for X=Br) or Bun (for X=OPh) at low tem-perature gives XMe2GeCLi(SiMe3)2 species which, on warming, eliminates LiX to give theunsaturated Me2Ge¼C(SiMe3)2 <2000CJC1412, 2000JOM(598)304>.
(ii) Two Si, one B, and one metal functions
The products obtained from the reaction between boriranylideboranes and [CoCp(C2H4)2] dependon the substituents at boron. For R=duryl (2,3,5,6-Me4C6H) or mesityl the dinuclear metalcomplexes 99 are formed (in 46% and 19% yields, respectively) but for R=But the mononuclearcomplex 100 is formed (Scheme 5) in 11% yield <1998CEJ44>.
(iii) One Si, one Ge, one B, and one metal functions. Also two Ge, one Si, and one metal functions.Also two Ge, one B, and one metal functions. Also Two B, one Si, and one metal functions.Also two B, one Ge, and one metal functions
Very few examples of compounds containing these functions seem to have been prepared.Compounds containing such functions should, however, be available from synthetic routesdescribed above in this section. In particular, such functions should be available from thereactions between suitably substituted lithium reagents and appropriate metal halides.
B
Co
C B But
Me3Si
Me3Si
But
B
C
Co
CMe3Si
Me3Si B
Co
R
Men
C
BB
RR
CMe3Si
Me3Si
2[CoCp(C2H4)2]2[CoCp(C2H4)2]
R = mesitylor duryl
99100
R = But
Scheme 5
Functions Containing at Least One Metalloid (Si, Ge, or B) 401
As would be expected from the ready metallations of trisilylmethane derivatives the digermyl-silylmethane (Me3Ge)2(FBu
t2Si)CH reacts with MeLi in THF/Et2O to give (Me3Ge)2(FBuFBu
t2-
Si)CLi, which, when treated with Me3SnCl, affords (Me3Ge)2(FBut2Si)CSnMe3 in 51% yield
<1996JOM(511)239>.
6.13.1.3 Methanes Bearing Two Metalloid and Two Metal Functions
6.13.1.3.1 Two Si and two metal functions
Metallation of BrMe2SnCBr(SiMe3)2 by PhLi affords BrMe2SnCLi(SiMe3)2 which, when warmed,eliminates LiBr to give first a stannene and then a cyclic dimer, 101, as shown in Scheme 6<2000JOM(598)292, 2000JOM(598)304>. A related bulky methyllithium derivative(Me3Si)2(PhMe2Sn)CLi was readily prepared via Sn�C bond cleavage of (Me3Si)2(PhMe2Sn)2Cby MeLi in THF/Et2O <1998JOM(564)215>.
Attempts have been made to prepare (Me3Si)2CLi2 by the pyrolysis of either the ate complex[Li(THF)4][Tsi2Li] or the solvent-free [TsiLi]2 (a method that works in the synthesis of (Me3Si)2-SiLi2 from (Me3Si)3SiLi) but they fail and give instead oligomeric products <1998MI222>.
6.13.1.3.2 Two Ge and two metal functions
There do not appear to be any compounds containing this function but they could, doubtless,be prepared in similar ways to the analogous Si2M2C-containing species described above inSection 6.13.1.3.1.
6.13.1.3.3 Two B and two metal functions
Compounds containing this grouping are relatively rare (see <1995COFGT(6)377> for earlywork in the area). A range of diboraallenes, 102, containing a four-coordinate planar carboncan be prepared according to Equation (15) from the anions 103 <2001AG(E)2662>. Syntheticapproaches to planar carbon atoms have often involved the preparation of compounds containingcarbons heavily substituted by metalloids or metals and this work has been reviewed in<1999CSR367>.
B C B R1R1
(Me3Si)2CHB C B
R1
R2
R1
R2
Li
Li
OEt2
OEt2
2 – ––
+ R2Li–(Me3Si)2CHLi
102
103 R1 = R2
= mesitylR1
= R2 = 2,3,5,6-Me4C6H
R1 = R2
= 2,6,-Me24-ButC6H2
R1 = mesityl, R2
= But
ð15Þ
C(SiMe3)2Me2SnBr Br
Et2OC(SiMe3)2Me2Sn
Br Li –LiBrC(SiMe3)2Me2Sn
Me2Sn(Me3Si)2C SnMe2
C(SiMe3)2
+ PhLilow temp.
x2
101
Warm
Scheme 6
402 Functions Containing at Least One Metalloid (Si, Ge, or B)
6.13.1.3.4 Other combinations of two metalloids and two metal functions
There are very few compounds known containing mixed metalloids and two metal functions.They should, however, be available by the routes described above for related compounds contain-ing two of the same metalloid. One notable example of this type of compound is racemic(Me3Pb)(Me3Sn)(Me3Ge)(Me3Si)C, a molecule containing all the elements of group 14 connectedtogether, which can be obtained from a series of metathesis reactions <B-1997MI251>.
6.13.1.4 Methanes Bearing One Metalloid and Three Metal Functions
6.13.1.4.1 One Si and three metal functions
Relatively few new compounds of this type have been prepared since those described in<1995COFGT(6)377>. The bulky dialkyltitanium complex 104 reacts with AlMe3 (Equation(16)) to give the four-coordinate carbide complex 105 in 78% yield <2001OM1175>.
TiCp N
PPri3
Si SiMe3Me3
TiCp
MeAlMe2
C
NAlMe2
SiMe3
PPri3
–3CH4
+ AlMe2CH2SiMe3
104105
3AlMe3
ð16Þ
6.13.1.4.2 One Ge and three metal functions
No new compounds containing this grouping seem to have been prepared since those described in<1995COFGT(6)377>.
6.13.1.4.3 One B and three metal functions
There seem to be few, if any, compounds of this type known. It may be possible to prepare suchspecies by the reaction of a methylidyne cluster with a borane, R2BH, in a manner similar to thatused in the preparation of silyl-substituted alkylidyne complexes.
6.13.2 METHANES BEARING FOUR METAL FUNCTIONS
6.13.2.1 Methanes Bearing Four Similar Metals
A slightly modified method for the preparation of (Me3Sn)4C from CCl4, Li, and Me3SnClhas been reported together with new spectroscopic data <1995JOM(496)241>. This compounddoes not seem to have been of use in synthesis but has been the subject of several detailedstructural studies (see, e.g., <1999MI385>). A method for obtaining very pure Hofmann’s base,[CHg4O(OH)2OH2]n, has been described <1996JOM(522)297>. The pure base can be used inthe preparation of C(HgNO3)4 and C(HgSO4)2(HgOH2)2.
6.13.2.2 Methanes Bearing Three Similar and One Different Metal Functions
Treatment of phosphinimide complexes 106 with excess AlMe3 leads to multiple C�H bondactivation and formation of the carbide complexes 107 in good yield (Equation (17))<2001OM1175>. (For the products from the analogous reaction with bulky alkyl substituentsat Ti see Section 6.13.1.4.1, and for their behavior in solution see Section 6.13.3.)
Functions Containing at Least One Metalloid (Si, Ge, or B) 403
TiCp1 N
PR3
Me MeTi
Cp1
MeAlMe2
C
NAlMe2
AlMe2
PR3
–3CH4
106, 107
3AlMe3
Cp1 = Cp; R = Cy or Pri
Cp1 = indenyl; R = Pri
ð17Þ
6.13.2.3 Methanes Bearing Two Similar and Two Different Metal Functions
Compounds containing this type of grouping seem to be very rare although carbons coordinatedby different metals may well occur in metal carbides, these are outside the scope of this chapter.
6.13.2.4 Methanes Bearing Four Different Metal Functions
Although there are a potential 135 751 different combinations (and their optical isomers) of 43different metals at a tetrahedral carbon center, very few seem to have been prepared. A compre-hensive search of the literature for such a large number of functional groups is clearly very difficultto carry out and it is quite possible that many such groupings have been missed in compiling thisarticle. It is hoped that any omissions of such groupings will not be serious for the organic chemist.
6.13.3 METHANES BEARING MORE THAN FOUR METALLOIDOR METAL FUNCTIONS
Polyhedral metallacarboranes in which carbon is bonded tomore than four metalloid or metal centersvia multicenter interactions are numerous but beyond the scope of this article. Reviews of metalla-carborane chemistry can be found in <2002CCC728, 2002CCR(231)23, 2000MCLC(342)7,1999JOM(581)1>. Variable temperature NMR studies show that the four-coordinate carbide com-plexes, 107 (see Section 6.13.2.2), are in equilibrium (Equation (18)) with five-coordinate complexes108 in the presence of AlMe3 <2000AG(E)3263>.
TiCp
MeAlMe2
C
NAlMe2
AlMe2
PR3
AlMe3
–AlMe3
TiMe N
CMe2Al
AlMe2
Me
Me2Al
AlMe2
Cp PR3
107
R = Pri or Ph108
ð18Þ
ACKNOWLEDGMENTS
This chapter is dedicated to Professor C. Eaborn, FRS, who died in February 2004. Much of thechemistry described above was initiated in the Eaborn group and the versatility of reagents, suchas (Me3Si)3CLi, that have now become popular across a wide range of organometallic chemistrywas demonstrated first in the research laboratories at Sussex University.
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Biographical sketch
Paul D. Lickiss was born in Kent, the Garden of England, studied atThe University of Sussex, where he obtained a B.Sc. degree in 1980 andhis D.Phil. in 1983 under the supervision of Professor C. Eaborn, FRS.After staying at the University of Toronto with Professor Adrian Brookfrom 1983 to 1984, he returned to Sussex and took up a position as aRoyal Society 1983 University Research Fellow in 1985. In 1989 heresigned his Fellowship to take up a position as a lecturer in the Uni-versity of Salford where he stayed for four years. From the 1990s, he hasbeen a Lecturer, Senior Lecturer, and now Reader in organometallicchemistry in the Synthesis Section in the Chemistry Department atImperial College, London. His research interests are mainly in the fieldof organosilicon chemistry, particularly the synthesis of low-coordinatecompounds such as silyl cations and the use of bulky groups to stabilizeunusual compounds. He is also interested in the synthesis and uses oforganosilanols, especially those containing several Si–OH groups. Theuse of ultrasound for synthesis is also actively pursued.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 381–408
408 Functions Containing at Least One Metalloid (Si, Ge, or B)
6.14
Functions Containing a Carbonyl
Group and at Least One Halogen
R. MURUGAN and S. V. YARLAGADDA
Reilly Industries Inc., Indianapolis, IN, USA
6.14.1 INTRODUCTION 4106.14.2 CARBONYL HALIDES WITH TWO SIMILAR HALOGENS 4106.14.2.1 Carbonic Difluoride 4106.14.2.2 Carbonic Dichloride 4116.14.2.2.1 Preparation of phosgene 4116.14.2.2.2 Phosgene alternatives 411
6.14.2.3 Carbonic Dibromide 4126.14.2.4 Carbonic Diiodide 412
6.14.3 CARBONYL HALIDES WITH TWO DISSIMILAR HALOGENS 4136.14.3.1 One Fluorine and Chlorine, Bromine, or Iodine 4136.14.3.1.1 Carbonic chloride fluoride 4136.14.3.1.2 Carbonic bromide fluoride 4136.14.3.1.3 Carbonic fluoride iodide 414
6.14.3.2 One Chlorine and Bromine or Iodine 4146.14.3.2.1 Carbonic bromide chloride 4146.14.3.2.2 Carbonic chloride iodide 414
6.14.3.3 One Bromine and Iodine 4146.14.3.3.1 Carbonic bromide iodide 414
6.14.4 CARBONYL HALIDES WITH ONE HALOGEN AND ONE OTHER HETEROATOM 4146.14.4.1 One Halogen and One Oxygen 4146.14.4.1.1 Fluoroformate esters 4156.14.4.1.2 Chloroformate esters 4156.14.4.1.3 Bromoformate esters 4196.14.4.1.4 Iodoformate esters 419
6.14.4.2 One Halogen and One Sulfur 4196.14.4.2.1 Fluorothiolformate esters 4196.14.4.2.2 Chlorothiolformate esters 4206.14.4.2.3 Bromothiolformate esters 4206.14.4.2.4 Iodothiolformate esters 420
6.14.4.3 One Halogen and One Nitrogen 4206.14.4.3.1 Carbamoyl fluorides 4216.14.4.3.2 Carbamoyl chlorides 4216.14.4.3.3 Carbamoyl bromides 4226.14.4.3.4 Carbamoyl iodides 422
6.14.4.4 One Halogen and One Phosphorus 4226.14.4.4.1 Chlorocarbonyl derivatives of phosphorus(III) 4226.14.4.4.2 Chlorocarbonyl derivatives of phosphorus(V) 423
6.14.4.5 One Halogen and One Arsenic, Antimony, or Bismuth 4236.14.4.6 One Halogen and One Metalloid (Boron, Silicon, or Germanium) 4236.14.4.7 One Halogen and One Metal 4246.14.4.7.1 Halocarbonyl complexes of first transition metal series (iron and chromium) 4246.14.4.7.2 Halocarbonyl complexes of second transition metal series (ruthenium and rhodium) 4246.14.4.7.3 Halocarbonyl complexes of third transition metal series (rhenium and iridium) 424
409
6.14.1 INTRODUCTION
The literature search was done using the general term carbonyl halides and other specificcompounds such as carbonyl difluoride, phosgene, chloroformates, etc., discussed by name inthis chapter. As observed by the authors, of COFGT (1995) <1995COFGT(6)407>, the presentauthors observed more literature on those compounds, when the halogen is chlorine. Forexample, there are more references on carbonyl dichloride than those on carbonyl difluoride,carbonyl dibromide, and carbonyl diiodide combined. Similarly in the case of halo formatederivatives there are more references on chloro formates than those on, fluoro-, bromo-, oriodo-formates.
The arrangement of sections and subsections is similar to that of COFGT (1995)<1995COFGT(6)407>, except some sections are not repeated as not much has changed betweenthen and the end of 2003. For example, the section on toxicity and handling of phosgene is notrepeated here. In the decade up to 2003, the trend has been towards the ‘‘green chemistry’’concept of alternative synthetic approaches for the titled functional groups that would replacetoxic substances like carbon monoxide and phosgene with other relatively less/nontoxic chemicalslike carbon dioxide.
6.14.2 CARBONYL HALIDES WITH TWO SIMILAR HALOGENS
The general preparations reported in <1995COFGT(6)407> on these carbonyl difluoride,dichloride, dibromide, and diiodide are summarized in Scheme 1. There are three general syn-thetic routes for these compounds. One of the methods is by halogen exchange reaction oncarbonyl chloride or phosgene using a halide source. The other two methods start from carbonmonoxide and halogen (carbon monoxide insertion into halogens works well for carbonyldifluoride and dichloride), and oxidation of a perhalogenated organic compound with an oxygenoxidant (works well for carbonyl dibromide).
6.14.2.1 Carbonic Difluoride
A novel approach to making carbonyl difluoride has been to react carbon dioxide and fluorinegas (Equation (1)). This method does not use toxic compounds such as phosgene and carbonmonoxide. Carbon dioxide and fluorine are allowed to react with each other in the gaseous state,to produce carbonyl difluoride, at a preferred temperature range of 150–250 �C with a mole ratioof 0.5:2, and near atmospheric pressure in a fluorine resistant metal, such as stainless steel, underanhydrous conditions <1999JAP11116216>.
+CO2 F2 COF2 ð1Þ
Carbonyl difluoride has been used in the synthesis of fluorinated methyl ethers<1995USP5382704> of the formula R2CHOCF2A where A is Cl or F, and each R is H,(CF2)nCl, (CF2)nF, or (CF2)nH (where n=1–10).
Dry etching of high-melting-point metals has been achieved by using carbonyl compounds,specifically that of carbonyl difluoride <1995JAP07221074>. This process has been useful forforming electrodes, circuits, etc.
Oxidant
2X–
CO COX2 CX4
COCl2
X2
Scheme 1
410 Functions Containing a Carbonyl Group and at Least One Halogen
6.14.2.2 Carbonic Dichloride
Carbonic dichloride or carbonyl dichloride or phosgene is the most important of all the functionalcompounds mentioned in this chapter. It is made commercially in large quantities and almost allthe other functional groups mentioned in this chapter could be obtained by chemical transforma-tions on phosgene. Phosgene is also a highly toxic and very reactive compound. It is anindustrially important compound, as it is used in the preparation of polyurethanes and poly-carbonates. Hence, it is the most studied of all the functional groups mentioned in this chapter. Inthe early 2000s, there is an awareness that phosgene should be replaced by other less toxicchemicals in the synthesis of polyurethanes and polycarbonates.
6.14.2.2.1 Preparation of phosgene
In general, phosgene has been prepared in three ways: the classical synthesis of insertion ofcarbon monoxide to chlorine; the chemical as well as photochemical oxidation of perchlorinatedcompounds; and the decomposition of other phosgene derivatives such as chloroformates andcarbonates which are also used as phosgene alternatives. All these methods have been discussed inCOFGT (1995) <1995COFGT(6)407>.
Phosgene is also produced as one of the products in the photocatalytic degradation of perha-logenated hydrocarbons on porous titanium oxide <2001AC(B)109, 2002MI412>.
A report on the synthesis of phosgene from triphosgene or bis(trichloromethyl)carbonate, alongwith the comparison of the reactivity of phosgene with that of diphosgene and triphosgene withmethanol, has been published <2000JOC8224>.
Phosgene can be manufactured from diphosgene and triphosgene using deactivated amines as thecatalysts. The amine catalysts are selected from poly(2-vinylpyridine), phenanthridine, phthalo-cyanines, and metallophthalocyanines free and on a polymer support, and poly(N,N-dimethyl-aminomethylstyrene) <1999GEP19740577>.
There are a few reports of carbon labeled phosgene synthesis, which were also discussedin COFGT (1995) <1995COFGT(6)407>. Even in the preparation of 11C-labeled phosgene tomake 11C-labeled ureas and isocyanates, alternatives like 11C-labeled carbon dioxide have beenused <1999MI537>. Another example of the use of 11C-carbon monoxide in place of labeledphosgene is in the preparation of 11C-carbamoyl compounds using selenium <2002JOC3687>.11C-Phosgene, a useful precursor for labeling several radiopharmaceuticals, is generally made bycatalytic oxidation of 11C-carbon tetrachloride over iron granules, although in low yields or withpoor reproducibility. Chlorination of 11C-methane followed by reaction with a stream of 98:2nitrogen/oxygen over iron has provided 11C-phosgene <2001MI785>. The yield of 11C-phosgenewas significantly increased by using iron oxide along with iron granules <2002MI345>.
A simple review of the history, preparation, and uses of phosgene was done by Senet<1998MI12>.
A modified production of phosgene from carbon monoxide and chlorine has been patented.This patent claims the use of a metal halide catalyst preferably selected from group III metals likealuminum and gallium <1999GEP19916856>.
An improved method for the preparation of phosgene in the laboratory has been reported. Inthis approach phosgene was prepared by addition of 95–98% sulfuric acid to a mixture ofphosphorus pentoxide and carbon tetrachloride <1998MI123>.
An interesting way to address the toxicity and safety issues associated with phosgene is the useof a microfabricated reactor for its manufacture. This is an example of the potential for safeon-site/on-demand production of a hazardous compound, in this case phosgene. Complete con-version of chlorine is observed for a 1:1 feed at 8 cc/min, which gives a projected productivity ofapproximately 100 kg/year from a 10-channel microreactor, with the opportunity to producesignificant quantities by operating many reactors in parallel <2001MI1639>.
6.14.2.2.2 Phosgene alternatives
Because of the toxicity and the high reactivity of phosgene, many alternatives have been madeand used as phosgene equivalents. Interestingly, most of them are made from phosgene but areeasier to handle than phosgene itself. The most common phosgene alternatives mentioned inCOFGT (1995) <1995COFGT(6)407> are summarized in Scheme 2.
Functions Containing a Carbonyl Group and at Least One Halogen 411
Ureas have been traditionally synthesized by methodologies mainly based on the use ofdangerous reagents such as phosgene and isocyanates. However, in the late 1990s and early2000s, these reagents have been increasingly substituted by cleaner and inherently safercompounds, referred to as phosgene substitutes, such as bis(4-nitrophenyl)carbonate, triphosgene,di-t-butyl-dicarbonate, 1,1-carbonylbisimidazole, 1,1-carbonylbisbenzotriazole, S,S-dimethyldithiocarbonate, and trihaloacetyl chlorides. These safer reagents could be stored and handledwithout special precautions <2000GC140>.
Phosgene has been replaced with carbon dioxide in the synthesis of alkyl carbonates. Mixedor symmetrical dialkyl carbonates were generated in high yields (53–97%) from alcohols,carbon dioxide, and alkyl chlorides in apolar aprotic solvents using guanidine bases under mildconditions <1995JOC6205>.
(i) Prepared from phosgene
The common phosgene alternatives are usually made from phosgene, replacing either one or bothof the chlorine atoms with a leaving group, and thus making the whole compound more stableand easier to handle. There are also reviews on the use of these phosgene alternatives. Forexample, the use of bis(trichloromethyl)carbonate or triphosgene in organic synthesis as a sub-stitute for phosgene is well reviewed <1996S553, 1994MI357>.
The preparation of N,N0-carbonyldiimidazole has been reported, starting from imidazole andphosgene. Reaction of imidazole with phosgene in toluene in the presence of tributylamine gave76% yield of N,N0-carbonyldiimidazole <2001MI33>.
6.14.2.3 Carbonic Dibromide
Carbon monoxide and bromine are reacted over activated carbon to give carbonyl dibromide(Equation (2)). Like phosgene, carbonyl dibromide is also used in the synthesis of compoundssuch as diaryl carbonates <1992EUP520238>. In the application on the use of carbonyl dibro-mide in the preparation of diaryl carbonates, aluminum trifluoride has been used as the catalyst<1992EUP516355>. Carbonyl dibromide is also used in the synthesis of metal bromides and theirbromide oxides <1997JCS(D)257>. This reaction of carbonyl bromide with metal oxides isfurther discussed in Section 6.14.4.7 on the halocarbonyl metal compounds.
+Activated “C”
CO Br2 COBr2ð2Þ
6.14.2.4 Carbonic Diiodide
This compound was not reported in COFGT (1995) <1995COFGT(6)407> and many attempts tomake this compound have failed. It was suggested that this may be due to its poor stability.However, it has been found that heating carbon tetraiodide in a stream of oxygen results in theformation of carbonyl diiodide, and this has been confirmed from its infrared (IR) spectrum(Equation (3)) <1995CPL594>. Carbonyl diiodide, which is similar to carbonyl difluoride, has
Diphosgene Triphosgene
Phosgene
N
N
NN O
Imidazole Methanol MethanolCOCl2 CH3OCOCl CH3OCOOCH3
CCl3OCOCl CCl3OCOOCCl3
Cl2 Cl2
Scheme 2
412 Functions Containing a Carbonyl Group and at Least One Halogen
been used in the decontamination of metal surfaces that are contaminated by metal oxides ofU, Pu, Np, Tc, etc. The metal oxides are converted into their iodides or carbonyl complexes,which are volatile and hence removed by vacuum <2001JAP153996>.
+CI4 O2 COI2 ð3Þ
6.14.3 CARBONYL HALIDES WITH TWO DISSIMILAR HALOGENS
The general syntheses of these compounds mentioned in COFGT (1995) are summarized inScheme 3 <1995COFGT(6)407>. The two major approaches are: the insertion of carbon mon-oxide with the mixed halogen compound, and halogen exchange with a halide ion source on acarbonyl dihalide with a different halogen.
6.14.3.1 One Fluorine and Chlorine, Bromine, or Iodine
6.14.3.1.1 Carbonic chloride fluoride
An improved method for the synthesis of carbonyl chloride fluoride under mild conditions hasbeen reported. Pure carbonyl chloride fluoride can be isolated in essentially quantitative yieldfrom the decomposition of the oxygen-bridged COCl2�SbF5 donor–acceptor adduct at roomtemperature (rt) in a dynamic vacuum <1999JFC(94)107> (Equation (4)). These adducts alongwith that of carbonyl chloride fluoride and penta fluoro compounds have been studied usingvibrational spectroscopy, nuclear magnetic resonance (NMR), mass spectra, and theoreticalcalculations <1997JCS(D)251, 1999IC3143>.
+COCI2.SbF5 O2 COClF ð4Þ
Carbonyl chloride fluoride is formed by thermal decomposition of chlorofluoro carbons likeCCl2F2 with titanium dioxide catalyst <1995JCA394> (Equation (5)), as well as by dielectricdischarge <1999MI627>. They are also formed by the oxidation of chlorofluoro carbons withozone <1992JPC8069> (Equation (6)).
+ Other products+CF2Cl2 O2 COFClTiO2 ð5Þ
+CFCl3 O3 COFCl ð6Þ
Carbonyl chloride fluoride is also formed in the oxidation of hydrofluorocarbons with eitherchlorine <1993MI179> or other oxidants <1993MI(66)97> (Equation (7)).
+ Cl. Cl. +CHFCl2 COFCl H3CCFCl2Air Air ð7Þ
6.14.3.1.2 Carbonic bromide fluoride
Photooxidation of tribromofluoromethane in an oxygen atmosphere containing ozone showed theformation of carbonyl bromide fluoride (Equation (8)) <1996JPC9271>. This compound likeother different carbonyl dihalides has been spectroscopically studied, specifically its NMR andmass spectra <1997JCS(D)251>.
CO COX1X2 COCl2–Cl–
X1X2 X1–
Scheme 3
Functions Containing a Carbonyl Group and at Least One Halogen 413
+CFBr3 O3 COFBr ð8Þ
6.14.3.1.3 Carbonic fluoride iodide
The synthesis of carbonic fluoride iodide was reported in COFGT (1995) <1995COFGT(6)407>by a reaction of iodine pentafluoride with carbon monoxide under pressure, and no new syntheticmethods for this compound have been reported, up to 2003.
6.14.3.2 One Chlorine and Bromine or Iodine
6.14.3.2.1 Carbonic bromide chloride
Carbonyl bromide chloride has been prepared by the insertion reaction of carbon monoxide withbromine chloride <1993USP5235000>, a readily available brominating reagent (Equation (9))<1999JPC2624>.
+BrCl CO COBrCl ð9Þ
Carbonyl bromide chloride has also been prepared by the photochemical oxidation ofbromochlorohydrocarbons such as, dibromochloromethane and bromodichloromethane, withozone (Equation (10)) <1999JCS(D)73, 1997JPC2074>.
++ Others+ H2CBrClO3HCBr2Cl O3 COBrCl ð10Þ
Like other carbonyl dihalides, carbonyl bromide chloride has been studied for its spectralbehavior, like that of NMR and mass spectra <1997JCS(D)251>.
6.14.3.2.2 Carbonic chloride iodide
As was the case in COFGT (1995) <1995COFGT(6)407>, carbonic chloride iodide has not yet(in late 2003) been reported.
6.14.3.3 One Bromine and Iodine
6.14.3.3.1 Carbonic bromide iodide
As in COFGT (1995) <1995COFGT(6)407>, no synthetic method for this compound, carbonicbromide iodide, has been reported, up to the end of 2003.
6.14.4 CARBONYL HALIDES WITH ONE HALOGEN AND ONE OTHERHETEROATOM
6.14.4.1 One Halogen and One Oxygen
The general methods used for the syntheses of these haloformate esters, reported in COFGT(1995), are summarized in Scheme 4 <1995COFGT(6)407>. The three possible approaches are:first, the nucleophilic displacement of one of the halogen of a dihalo carbonyl with an alcohol togive the haloformates; second, the insertion of carbon monoxide on organo hypohalites; andthird, the halogen exchange reaction of one haloformate ester to another haloformate ester byusing a halide ion source.
414 Functions Containing a Carbonyl Group and at Least One Halogen
6.14.4.1.1 Fluoroformate esters
A method for the production of aliphatic fluoroformates, where carbonyl fluoride is esterifiedwith aliphatic alcohols (e.g., t-butanol) in an ether at �20 �C to +50 �C, is described. The methodis carried out using carbonyl fluoride obtained by reacting phosgene with surplus powderedsodium fluoride whose granules have a specific surface of �0.1m2 g�1 and/or anaverage diameter of �20 mm. This method enables the preparation of unstable fluoroformates(e.g., t-Bu fluoroformate) in excellent yields (Equation (11)) <2000WOP0059859>.
+OH OCOF
COCl2NaF ð11Þ
One of the fluoroformates, 9-fluorenylmethyl fluoroformate, is a useful reagent for the largescalesynthesis of dipeptide-free Fmoc (9-fluorenylmethoxycarbonyl) amino acids. 9-Fluorenylmethylfluoroformate (Fmoc-F) is an inexpensive and effective reagent, which is available in large quan-tities for the synthesis of Fmoc-amino acids <1998MI244>.
6.14.4.1.2 Chloroformate esters
Next to phosgene, chloroformate esters are the most important industrial compounds consideredin this chapter. Significant research has been done on the transformation of these compounds intoother compounds. Chloroformates are much easier to handle than phosgene and the difference inreactivity of the two leaving groups has been exploited in its chemistry. Diphosgene or trichloro-methyl chloroformate, a versatile reagent in organic synthesis, is reviewed. Its reactions withamines, alcohols, and others have been discussed <1992MI230>. Similarly, another chlorofor-mate, methyl chloroformate, has been reviewed for its chemistry as well as its hazardous nature<1994MI181>. As mentioned earlier, because of its importance as an industrial chemical,procedures for the storage and transport of chloroformate esters with reduced decompositionare well documented and regulated. For example, using polymer surface coatings of polyethylenefor storage vessels as well as transport pipes decreases the decomposition of ethyl chloroformate<2002GEP10102807>.
Chloroformates with the simplest alkyls, such as methyl, ethyl, or isobutyl, are used as generalderivatizing agents in gas chromatography. The use of chloroformates in this regard in variousdisciplines has been reviewed <1998JC57>.
The preparation and application of chloroformates, for the immobilization of enzymes, havebeen described <1995ANY391>.
(i) From phenols and phosgene
A continuous process is reported for the preparation of monofunctional aromatic chloroformates.Thus para-cumylphenol in methylene chloride reacted with phosgene in the presence of excess ofaqueous sodium hydroxide gave a very good yield of the chloroformate with trace amounts of thediaryl carbonate impurity <2000WOP0058259> (Equation (12)). Other similar approaches arealso known <2001WOP0132598, 1994JAP06135900, 1994USP5332841, 1993RUP1240016,1993RUP1235148, 1996EUP743298, 2000WOP0051964>.
+
COX2
ROCOX1
ROHROCOX CO
ROCl
X1–
X–
–HX
Scheme 4
Functions Containing a Carbonyl Group and at Least One Halogen 415
OH
+
O Cl
O
COCl2NaOH
ð12Þ
Synthesis and application of 3,5-di-t-butylbenzyl chloroformate for the protection of aminofunctions and the improvement of solubility in polyurethane synthesis have been reported<1999JPR29> (Equation (13)).
OH
+O Cl
O
COCl2NaOH
ð13Þ
Arylene bis(chloroformates), precursors for cyclic oligomeric carbonate monomers, are pre-pared by three methods: using PhNEt2 to scavenge HCl, by low pH, low-temperature interfacialcondensation of bisphenols with phosgene, and using Ca(OH)2 in interfacial condensation withphosgene <1995MI179> (Equation (14)).
OH
+
O Cl
O
OH O Cl
O
2COCl2AIBN ð14Þ
Chiral resolution of 1,10-binaphthalene-2,20-diol and its (�)-menthyl chloroformate derivativesby high-performance liquid chromatography has been reported using the urea derivative as achiral stationary phase <2002MI217>.
(ii) From alcohols and phosgene
Chloroformates are prepared by dissolution of water-soluble alcohols having a melting point�20 �C in H2O and reaction with phosgene. Trimethylolpropane reacted with phosgene in H2Ounder ice cooling for 1 h to give 72% trimethylolpropane trischloroformate <2000JAP273066>(Equation (15)).
+
CH2OH
CH2OHCH2OH
CH2OCOCl
CH2OCOClCH2OCOCl3COCl2 ð15Þ
Chloroformates are prepared by treating alcohols with molecular sieves followed by reactionwith phosgene. Thus, s-butyl alcohol was treated with molecular sieves at room temprature for15 h, and reacted with phosgene to give 96% s-butyl chloroformate <1999JAP11302230>(Equation (16)).
+OH OCOCl
COCl2 ð16Þ
Chloroformates have also been prepared by phosgenation of alcohols under pressure<1999WOP9911597>, under reduced pressure <2002EUP1216983>, as well as in the presenceof activated carbon <1999GEP19737329>. Under the reduced pressure conditions, phosgene hasbeen replaced by either diphosgene or triphosgene <2002EUP1216983>.
416 Functions Containing a Carbonyl Group and at Least One Halogen
Hydroxyalkyl (meth)acrylate chloroformates are prepared by reaction of hydroxyalkylated acry-late or methacrylate esters with chloroformylation agents in the presence of H2O. 2-Hydroxyethylmethacrylate was treated with COCl2 in the presence of H2O at 0 �C for 2h to give 78%chloroformate <1998JAP10130205> (Equation (17)).
CH3
+
O
OOH
CH3
O
OOCOCl
COCl2NaOH
ð17Þ
Purification of methacryloyl-terminated chloroformates is done in high yields by mixing themwith hydrocarbon solvents and removing polymerized product by filtration <2001JAP288145>.
A convenient process for the synthesis of glyoxylate-derived chloroformates has been devel-oped. The approach involves the reaction of glyoxylate esters with triphosgene and pyridine invarious solvent systems. These novel glyoxylate-derived chloroformates are multifunctional,possessing a chloroformate, ester, and haloalkyl moiety <2002S365>.
The synthesis of benzyl chloroformate from benzyl alcohol and phosgene was studied. Theapplication of benzyl chloroformate in polypeptide synthesis has been introduced <2001MI35>.
(iii) Chlorination of carbonate
Trichloromethyl chloroformate is prepared from methyl formate or methyl chlorocarbonate inreactor under stirring using an ultraviolet (UV) high-pressure mercury lamp <1998PRP1172102>(Equation (18)).
+CH3OCOOCH3 Cl2 Cl3COCOCl ð18Þ
(iv) Preparation of �-halogenated chloroformates from aldehyde and phosgene
�-Chlorinated chloroformates, useful as pharmaceutical intermediates, are prepared by the reac-tion of phosgene with an aldehyde in the presence of a catalyst comprising alkyl-substitutedguanidines, hexa-substituted guanidinium chlorides, or bromides. Thus, acetaldehyde reacted withphosgene in the presence of pentabutylguanidine, producing 1-chloroethyl chloroformate in88.9% yield <1998USP5712407> (Equation (19)). Similarly, benzaldehyde-derived chlorofor-mates have also been made and used in the synthesis of novel insecticides <2001TL7751>.
+O
H
O
Cl
Cl
OCOCl2 ð19Þ
(v) Preparation of �-halogenated chloroformates by halogenation of chloroformates
An improved process for concurrently preparing 1-chloroethyl chloroformate and 2-chloroethylchloroformate with improved selectivity, was achieved by chlorination of ethyl chloroformate,optionally in presence of a free radical initiator. Ethyl chloroformate was chlorinated withchlorine gas in the presence of a free radical initiator 2,2-azobis(2-methylpropanenitrile) to givea mixture of 1-chloroethyl- and 2-chloroethyl-chloroformate <1994USP5298646>.
Preparation of trichloromethyl chloroformate has been achieved by a photochemical chlorina-tion process of methyl chloroformates. For example, this process comprises adding PCl5 tomethyl chloroformate and heating to 30–50 �C under light, treating with chlorine for 70–80 hwhile absorbing HCl with lime water <1998PRP1192434> (Equation (20)).
+CH3OCOCl PCl5 Cl3COCOCl ð20Þ
Preparation of chloromethyl chloroformate was done by free radical chlorination, using sulfurylchloride and 2,20-azobisiobutyronitrile (AIBN), of methyl chloroformate. The product, chloro-methyl chloroformate, thus obtained was reacted with alcohols to give alkoxycarbonyloxymethyl
Functions Containing a Carbonyl Group and at Least One Halogen 417
chlorides as intermediates for pharmaceuticals <1996JAP08040986> (Equation (21)). Chloro-methyl chloroformate has also been used in the synthesis of trichloroacryloyl chloride<1993MI001>.
+CH3OCOCl SO2Cl2 ClCH2OCOCl ð21Þ
(vi) Nonphosgene methods
Chloroformate esters are prepared by treating 1mol of HCl or nitrosyl chloride with 0.1–100 mol ofnitrite esters and CO in the presence of Pt-group metal catalysts. A mixture of HCl, CO, MeONO,NO, and MeOH (0.6:6:7:2:8) was passed through PdCl2/alumina at 60 �C to give 100% ClCO2Me<1994JAP06306017> (Equation (22)).
++ + +HCl CO MeONO NO MeOH MeOCOClPdCl2/Al2O3 ð22Þ
Chloroformate esters are also prepared by treating 1mol of chlorine with 0.1–100mol of nitriteesters and CO in the presence of supported Pt-group metal catalysts. A mixture of chlorine, CO,MeONO, NO, and MeOH (1:7:6:2:6) was passed through PdCl2/alumina at 120 �C to give 18%ClCO2Me (based on chlorine) <1994JAP06306016>. Similar preparations are reported for thesynthesis of alkyl chloroformate where the methyl nitrite has been replaced with alkyl nitrite ester<1994BCJ2554>.
Methyl chloroformate has been synthesized via direct interaction of palladium bis(methoxy-carbonyl) complexes with CuCl2 <1993JOM243> (Equation (23)). ClCOOMe has been obtainedin 80% yield by reaction of [PdL2(COOMe)2] [L2=2,20-bipyridine (bipy) or 1,10-phenanthroline(phen)] with CuCl2.
+ MeOCOClTHF
[Pd (bipy) (COOMe)2] 4CuCl2 ð23Þ
Benzyl chloroformate synthesis using carbon monoxide as a carbonyl source has been reported<2002T10011>. A novel nonphosgene synthetic method for benzyl chloroformate has beenestablished. S�Me O–benzyl carbonothioates were prepared by the carbonylation of benzylalcohols with carbon monoxide and sulfur (or carbonyl sulfide) in the presence of 1,5-diazabi-cyclo[5.4.0]undec-5-ene (DBU) followed by esterification using methyl iodide in good yields.Then, the benzyl chloroformates were successfully synthesized by the chlorination of S�MeO–benzyl carbonothioates using sulfuryl chloride in excellent yields (Equation (24)).
CH2OH
+
CH2OCOSMeS/DBU
CH2OCOCl
COSCl2 ð24Þ
A novel synthetic method for benzyl chloroformate using carbon monoxide or carbonyl sulfideas a carbonyl source has been established. Benzyl chloroformate was successfully synthesized bythe chlorination using sulfuryl chloride of PhCH2O2CSMe, which was prepared by the carbonyla-tion of benzyl alcohol with carbon monoxide and sulfur (or carbonyl sulfide) in the presence ofDBU (1,5-diazabicyclo[5.4.0]undec-5-ene) followed by esterification using methyl iodide<2002TL7765>.
(vii) Other chloroformates
An oxime of an estradiene derivative was reacted with phosgene or diphosgene to give achloroformate derivative <2002GEP10056677> (Equation (25)).
418 Functions Containing a Carbonyl Group and at Least One Halogen
ORCH2OR
O
H
NHO
Me
H
ORCH2OR
O
H
NO
Me
H
Cl
O
COCl2 ð25Þ
Methyl 11C-labeled methyl chloroformate, a novel 11C-acylating agent, was formed by thereaction of 11C-labeled methanol and phosgene <1995MI365>.
6.14.4.1.3 Bromoformate esters
From COFGT (1995) <1995COFGT(6)407> it is known that these compounds, bromoformateester, are prepared by two approaches. One using the reaction of alcohols with carbonyl dibro-mide, and two using the bromide exchange reaction on the chloroformates. Up until the end of2003, no new approaches have been reported for making bromoformate esters.
6.14.4.1.4 Iodoformate esters
Stable iodoformates were reported in COFGT (1995) <1995COFGT(6)407>. The first iodofor-mate, 9-triptycyl iodoformate, was made photochemically from its 9-triptycyl monoester of oxalicacid. Iodoformates have also been synthesized by using the iodide exchange reaction on chloro-formates. Up until the end of 2003, there have not been any new approaches to the synthesis ofiodoformates.
6.14.4.2 One Halogen and One Sulfur
Similar to the oxygen system of haloformate esters, here again in the halothiolformate esters thesynthetic methods mentioned in COFGT (1995) <1995COFGT(6)407> are summarized inScheme 5. The insertion of carbon monoxide to sulfenyl halide, the nucleophilic displacementof one of the halogen in carbonyl dihalide with a thiol, and the halogen exchange on ahalothiolformate are the three general routes to halothiolformate esters.
Structures and conformations of (fluorocarbonyl)trifluoromethylsulfane and that of (chloro-carbonyl)trifluoromethylsulfane have been determined by gas electron diffraction, vibrationalspectroscopy, and theoretical calculations <1997JPC2173>.
6.14.4.2.1 Fluorothiolformate esters
The preparation of fluorocarbonyl sulfenyl bromide from fluorocarbonyl sulfenyl chloride andtrimethylsilyl bromide was described in COFGT (1995) <1995COFGT(6)407>. A photochemical
X1
+
COX2
RSCOX1
RSHRSCOX
X–
CORSCl
–
–HX
Scheme 5
Functions Containing a Carbonyl Group and at Least One Halogen 419
study has been done with this compound. Under photochemical conditions, this fluoro-thiolformate ester eliminates carbon monoxide to give sulfur bromide fluoride <1993IC948>.
6.14.4.2.2 Chlorothiolformate esters
Here one should be careful not to confuse the thiono formates, with sulfur in the thiocarbonylgroup (C¼S), with that of thiol formates, with sulfur in the thiol group (C�S�). In some casesthe thiono formates could rearrange to thiol formates as seen with the allylic thiono chlorofor-mates.
(i) From phosgene and thiols
Thiochloroformates are manufactured with reduced amount of by-products by reacting thiolswith phosgene in the presence of ureas as a catalyst. For example, phosgene and n-octanethiolwith N,N-dimethylpropyleneurea as the catalyst, gave mainly n-octylthio chloroformate with verysmall amounts of thiocarbonate and disulfide as impurities <1999GEP19737619>.
(ii) By rearrangement of allylic thionochloroformates
Treatment of allylic alcohols with thiophosgene and pyridine gives thiolo chloroformates directlyat rt, presumably via a very rapid [3,3]-sigmatropic rearrangements of thionochloroformates.Synthesis of allyl thionochloroformate from allyl alcohols sodium hydride and thiophosgene atlow temperature and warming up to rt supports this finding <1999TL8059>.
Thiophosgene, as seen above, has been used in the synthesis of thiochloroformates. Generalreviews on the industrial synthesis of thiophosgene and derivatives are available <1998MI252,1997OPRD240>.
6.14.4.2.3 Bromothiolformate esters
These compounds, bromothiolformate esters, have rarely been reported <1995COFGT(6)407>.Bromide exchange on a fluorothiolformate has been reported to make trifluoromethyl bromothiol-formate and carbon monoxide insertion on methylsulfenyl bromide has been used to make methylbromothiolformate. Up until the end of 2003, new methods for the synthesis of bromothiolformateesters were not found in the literature.
6.14.4.2.4 Iodothiolformate esters
Similarly to what was reported in COFGT (1995) <1995COFGT(6)407>, the present authors didnot find any reference to this class of compounds in the period up to 2003.
6.14.4.3 One Halogen and One Nitrogen
The general methods reported in COFGT (1995) <1995COFGT(6)407> for the preparation ofthe above-mentioned compounds are summarized in Scheme 6. The reaction of carbonyl dihalidewith primary, secondary, and tertiary amines leads to carbamoyl halides, which in the case of aprimary amine could further be converted into isocyanates, an important industrial compound.The secondary amine carbamoyl halides could also be synthesized from either carbon monoxideinsertion into dialkyl haloamines, or halogenation of N,N-dialkyl formamides. Halo cyanato andhalo thiocyanato carbonyl compounds are made by nucleophilic displacement of the correspond-ing anions source with a carbonyl dihalide.
420 Functions Containing a Carbonyl Group and at Least One Halogen
6.14.4.3.1 Carbamoyl fluorides
Carbamoyl fluorides formed by the addition of hydrogen fluoride on to an isocyanate are used asfluorinating agents, specifically for converting a chloride into a fluoride. For example, para-(trifluoromethyl)phenyl isocyanate is prepared from para-(trichloromethyl)phenyl isocyanateand hydrogen fluoride in the presence of tin tetrachloride. A carbamoyl fluoride is suggested asthe intermediate in this reaction, which is isolated in small amounts from the reaction mixture<2002WOP0255487> (Scheme 7).
Experimental and theoretical investigations of the geometry and conformation of fluorocarbo-nyl isocyanate and fluorocarbonyl azide were carried out. These were compared with that of theircorresponding precursors, formyl isocyanate and formyl azide, respectively. The present authorswarn that fluorocarbonyl azide is an explosive and should be handled only with proper safetyprecautions and in millimolar quantities <1993JST197>.
N-fluoroformyliminotrifluoromethylsulfur fluoride, FCON¼S(F)CF3, has been studied usingvibration spectroscopy and theoretical calculations <2000MI881>.
6.14.4.3.2 Carbamoyl chlorides
Carbamoyl chlorides have also been made using the phosgene substitute, trichloromethyl carbo-nate or triphosgene. The effects of solvent, reaction time and temperature, feed ratio, and dosageof nucleophile on the yield have been discussed <2000MI16>.
Solid-phase synthesis of ureas of secondary amines via carbamoyl chloride has been reported.Secondary amines attached to a solid support such as the Wang resin can be converted to thecorresponding carbamoyl chlorides by treatment with phosgene or triphosgene <1997TL1895>.
R1R2R3N+COCl
R1R2NCOCl
COCl2 RNHCOClRNH2
R1R2NH
R1R2NCOH
COR1R2NCl
Cl2
R1R2R3N
Cl–
OCNCOCl
NCO–
SCNCOCl
SCN–
RNCOHCl
Scheme 6
N
CCl3
+
HN
CCl3
C
O
F
OHN
CF3
F
O
N
CF3
CO
+
97% 3%
HFSnCl4
Scheme 7
Functions Containing a Carbonyl Group and at Least One Halogen 421
A novel synthesis of 3-substituted 1-chlorocarbonylimidazolidin-2-ones using triphosgene orbis(trichloromethyl)carbonate has been reported. The yields and purity of the products obtainedare better than those obtained by a conventional method using phosgene <2000JCR(S)440,2000OPP498>.
New and efficient palladium-catalyzed routes to carbamoyl chlorides have been reported. Thepalladium-based catalytic system is very active and operates in two steps, avoiding the synthesis ofphosgene, but making use of carbon monoxide and chlorine as in phosgene chemistry. Primaryamines lead directly to isocyanates and the secondary amines lead to carbamoyl chlorides<2000OM3879>.
6.14.4.3.3 Carbamoyl bromides
Carbamoyl bromides or N-bromocarbonyl compounds have been made as reported in COFGT(1995) <1995COFGT(6)407> using the general methods used for the preparations of carbamoylhalides. The addition of hydrogen bromide to an isocyanate or the exchange of chloride incarbamoyl chlorides with a bromide source are the two common approaches to the synthesis ofcarbamoyl bromides. Up until the end of 2003, new methods for the synthesis of carbamoylbromides have not been seen in the literature.
6.14.4.3.4 Carbamoyl iodides
These compounds are suggested to be not very stable according to COFGT (1995)<1995COFGT(6)407>. Only one approach, that of addition of hydrogen iodide to an isocyanate,has been reported for the synthesis of carbamoyl iodides. There have been no new reports on thesynthesis of this class of compounds, up to the end of 2003.
6.14.4.4 One Halogen and One Phosphorus
Synthesis of compounds belonging to this section, mentioned in COFGT (1995)<1995COFGT(6)407>, is summarized in Scheme 8. The trivalent phosphorus compounds couldfurther react either by elimination of CO to give phosphorus halide, or by elimination ofhydrogen halide to give phosphaketene. The reaction of trisalkoxy phosphorus with carbonyldihalide gives alkyl halide and (dialkoxyphosphinyl)formyl halide, a pentavalent phosphoruscompound (Arbuzov reaction).
6.14.4.4.1 Chlorocarbonyl derivatives of phosphorus(III)
The reaction of triphenylmethyl-substituted primary and secondary phosphines with phosgene hasbeen studied. The nature of the product with the trityl-substituted primary phosphine depends onthe nature of the solvent. In toluene, the initially formed chlorocarbonyl phosphorus compound isstable, but it loses CO in methylene chloride to give a chlorophosphine, and loses HCl in ether
R2 = H
+ +
R1R2PSiMe3
R1P=C=O
COCl2R1R2PCl
(RO)3P
R1R2PCOCl
COCl2 (RO)2POCOCl RCl
Scheme 8
422 Functions Containing a Carbonyl Group and at Least One Halogen
solvent to give a phosphaketene, which dimerizes. In the case of the trityl-substituted secondaryphosphine, the nature of the product depends on the nature of the second substituent onphosphorus. When the substituent was phenyl, the initial adduct, chlorocarbonyl phosphoruscompound, was very stable, and when the substituent was a t-butyl the initial adduct readily lostthe CO to give the corresponding chlorophosphine compound <1999ZAAC1979>. In the samepaper the reaction of diphosphine with phosgene was reported. It was found to be inert in theabsence of hydrogen chloride. In the presence of HCl the P�P bond was cleaved to give theprimary phosphine and the chlorophosphine as the products <1999ZAAC1979>. All thesereactions are summarized in Scheme 9.
Another way these chlorocarbonyl phosphorus compounds have been made is via anhydrousHCl hydrolysis of phospha–urea compound, where the cleavage of a P�CO bond occurs leadingto a phosphine and a chlorocarbonyl phosphorus compound. This reaction is depicted inScheme 10 <1999ZAAC919>.
6.14.4.4.2 Chlorocarbonyl derivatives of phosphorus(V)
A facile one-pot preparation of phosphonothiolformates, useful reagents for the synthesis ofcarbamoylphosphonates, was accomplished by sequential reaction of phosgene solution withalkane thiols, to form the chlorothiolformates, followed by Arbuzov reaction with trialkylphos-phites <2000SL815>.
6.14.4.5 One Halogen and One Arsenic, Antimony, or Bismuth
As in COFGT (1995) <1995COFGT(6)407> any reports on these compounds were not seen.
6.14.4.6 One Halogen and One Metalloid (Boron, Silicon, or Germanium)
Preparation of this class of compounds has not been reported, in the period up to 2003, as wassimilarly observed in COFGT (1995) <1995COFGT(6)407>.
COCl2/CH2Cl2 COCl2/ether
+
COCl2/ toluene
R = But
+
Ph3CPHCOCl
Ph3CPHCOCl
Ph3CPHCOCl
Ph3CPRCOClCOCl2
Ph3CPRH
Ph3CPH2
–CO
Ph3PHCl
–HCl
(Ph3CPCO)2
Ph3CPRClPh3CPCl2COCl2
R = Ph
(Ph3CPH)2
COCl2
HClPh3CPH2 Ph3CPHCl
Scheme 9
+(Ph3CPH)2COHCl
Ph3CPH2 Ph3CPHCOCl
Scheme 10
Functions Containing a Carbonyl Group and at Least One Halogen 423
6.14.4.7 One Halogen and One Metal
The organometal carbonyls reactions with halogens are known to give organometal carbonylhalides <1995COFGT(6)407>. These compounds could further lose carbon monoxide to giveorganometal halides.
The synthesis of metal bromides and their bromide oxides by the use of carbonyl dibromidemust have gone through bromocarbonyl metal intermediates. Carbonyl dibromide reacted with awide selection of d- and f-block transition-metal oxides to form either the metal bromide orbromide oxide. The reaction was done, by heating the metal oxides at 125 �C for 10 days withexcess carbonyl dibromide in a sealed tube. Under these conditions V2O5, MoO2, Re2O7, Sm2O3,and UO3 were converted into VOBr2, MoO2Br2, ReOBr4, SmBr3, and UOBr3, respectively<1997JCS(D)257>.
No new synthetic method for this class of compounds has been seen in the period 1993–2003.All the references were to complexes with halogens and carbonyls attached directly to the metals,which are beyond the scope of this chapter.
6.14.4.7.1 Halocarbonyl complexes of first transition metal series (iron and chromium)
No new synthetic methods for this class of compounds have been reported in the period1993–2003, other than those mentioned in COFGT (1995) <1995COFGT(6)407>.
6.14.4.7.2 Halocarbonyl complexes of second transition metal series (ruthenium and rhodium)
No new synthetic methods for this class of compounds have been reported in the period1993–2002, other than those reported in COFGT (1995) <1995COFGT(6)407>.
6.14.4.7.3 Halocarbonyl complexes of third transition metal series (rhenium and iridium)
No new synthetic method for this class of compounds have been reported, other than thosementioned in COFGT (1995) <1995COFGT(6)407>, briefly discussed above.
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Biographical sketch
Ramiah Murugan was born in Madurai, India.He obtained B.Sc. in chemistry in 1975 fromAmerican College, Madurai, Tamil Nadu,India and an M.Sc. in chemistry in 1977 fromMadurai University. After four years of JuniorScientist work at Madurai University, he joinedProfessor A. R. Katritzky’s group at the Uni-versity of Florida, USA and obtained hisPh.D. in 1987. He stayed there for two moreyears doing postdoctoral work in the area ofhigh-temperature aqueous organic chemistry.He joined Reilly Industries in 1989 and iscurrently a Senior Research Associate. Hisresearch interests include synthesis of inter-mediates for pharmaceuticals, agrochemicalproducts, and performance products; mechan-istic studies; catalysis; polymer chemistry; andprocess development.
Subbarao Yarlagadda received his M.Sc. inorganic chemistry from Andhra University,Waltair, India. He obtained his Ph.D. in1991 from the Indian Institute of ChemicalTechnology (IICT), Hyderabad, India. Hisdoctoral work was chiefly on selective organictransformations by using a new class of het-erogenized homogeneous catalysts. Later, hejoined as a postdoctoral fellow with ProfessorM. Graziani at the University of Trieste, Italyunder the UNIDO program, and worked onpolydentate ligands and their metal complexesfor an oxidative amination reaction. From1992 to 1996, he was a staff scientist inDr. A.V. Ramarao’s group at IICT, India,and worked on the synthesis of fine and speci-alty chemicals, pharmaceutical intermediatesby using zeolite catalysts. In 1996, he joinedProfessor P. A. Jacobs at the Katholieke Uni-versity of Leuven, Belgium and worked onMesoporous zeolites and homogeneous cata-lysts for the synthesis of specialty chemicals.Since July 1998, he has been with ReillyIndustries, Indianapolis, IN, USA as aResearch Associate. His current interestsinclude the process development, inventionof new routes for the existing products, synth-esis of fine and specialty chemicals, develop-ment of new catalysts for the synthesis ofpharmaceutical and agrochemical intermedi-ates, and vitamins.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 409–427
Functions Containing a Carbonyl Group and at Least One Halogen 427
6.15
Functions Containing a Carbonyl
Group and at Least One Chalcogen
(but No Halogen)
H. ECKERT
Technical University Munich, Garching, Germany
6.15.1 CARBONYL CHALCOGENIDES WITH TWO SIMILAR CHALCOGEN FUNCTIONS 4306.15.1.1 Two Oxygen Functions 4306.15.1.1.1 Carbonates from phosgene and substitutes, chloroformates 4306.15.1.1.2 Carbonates from carbon oxides and carbonate salts 4326.15.1.1.3 Carbonates from ureas 4336.15.1.1.4 Cyclic carbonates and transesterification 4336.15.1.1.5 Acylcarbonates 4346.15.1.1.6 Carbonates by iodolactonization 4346.15.1.1.7 Polycarbonates 435
6.15.1.2 Two Sulfur Functions 4356.15.1.2.1 Dithiocarbonates by [3,3]-sigmatropic rearrangement 4356.15.1.2.2 1,3-Dithiol-2-ones by xanthogen disulfide-alkyne cycloaddition 4356.15.1.2.3 Mixed methods 436
6.15.1.3 Two Selenium Functions 4366.15.2 CARBONYL CHALCOGENIDES WITH TWO DISSIMILAR CHALCOGENIDE ATOM
FUNCTIONS 4366.15.2.1 Oxygen and Sulfur Functions 4366.15.2.1.1 Thiocarbonates from activated carbonates 4366.15.2.1.2 Thiocarbonates from alkoxycarbonylsulfenyl chlorides 4376.15.2.1.3 Thiocarbonates from carbonothioic acid salts 4376.15.2.1.4 Other methods 438
6.15.2.2 Other Dissimilar Chalcogenide Functions 4386.15.2.2.1 Oxygen and selenium functions 4386.15.2.2.2 Oxygen and tellurium functions 4396.15.2.2.3 Sulfur and selenium functions 440
6.15.3 CARBONYL CHALCOGENIDES WITH A CHALCOGEN FUNCTION AND ONE OTHERHETEROATOM FUNCTION 440
6.15.3.1 Oxygen and Nitrogen Functions 4406.15.3.1.1 Carbamates from chloroformates or phosgene equivalents 4406.15.3.1.2 Carbamates from isocyanates 4416.15.3.1.3 Carbamates from N,N0-carbonyldiimidazole (CDI) 4416.15.3.1.4 Carbamates from carbonates or dicarbonates 4426.15.3.1.5 Carbamates from carbon oxides 4436.15.3.1.6 Carbazates 4446.15.3.1.7 Azidoformates 444
6.15.3.2 Oxygen and Phosphorus Functions 4446.15.3.2.1 Phosphinecarboxylates by the Arbuzov reaction and related methods 444
6.15.3.3 Oxygen and Other Heteroatom Functions 4456.15.3.3.1 Oxygen and boron functions 445
429
6.15.3.4 Sulfur and Nitrogen Functions 4456.15.3.4.1 Thiocarbamates from chlorothioformates and amines 4456.15.3.4.2 Thiocarbamates from carbamoyl chlorides and thiols 4456.15.3.4.3 Thiocarbamates from isothiocyanates and alcohols 4466.15.3.4.4 Thiocarbamates from alkylamide salts, carbon monoxide, and sulfur 4466.15.3.4.5 Thiocarbamates from [3,3]-sigmatropic rearrangement 4466.15.3.4.6 Thiocarbamates from trichloroacetyl chloride, thiols, and amines 447
6.15.3.5 Sulfur and Phosphorus Functions 4476.15.3.5.1 Phosphonothioformates 447
6.15.3.6 Other Mixed Systems 4476.15.3.6.1 Selenium and nitrogen functions 4476.15.3.6.2 Tellurium and nitrogen functions 449
6.15.1 CARBONYL CHALCOGENIDES WITH TWO SIMILARCHALCOGEN FUNCTIONS
An overview on all functional group transformations, which can be accomplished by use ofphosgene as well as by use of about 70 phosgene substitutes and equivalents, has been presentedin 2003 by Cotarca and Eckert in Phosgenations—A Handbook <B-2003MI615-01>.
6.15.1.1 Two Oxygen Functions
Carbonic acid is principally a difunctional carboxylic acid; therefore, manifold preparativeaccesses for a great variety of its organic derivatives exist, which differ widely in rate andselectivity of reactions and reagents. Some reviews have been published <B-2003MI615-02,2000T8207, 1996CRV951, 1983HOU(E4)66>.
6.15.1.1.1 Carbonates from phosgene and substitutes, chloroformates
Phosgene, <B-2003MI615-01, 1964CRV645, 1973CRV75, B-1991MI615-01> as the formalcarboxylic acid dichloride of carbonic acid, is a highly reactive reagent, which affords highturnovers and good yields. Thus, both symmetrical and unsymmetrical dicarbonates, the lattervia chloroformates, can easily be produced.
A key intermediate of the decalin part of azadirachtin, an antifeedant, insect growth regulatory, andreproductive effective substance from the Neem treeAzadirachta indica, has been prepared by carbonyl-ation of the alcohol with methyl chloroformate, affording the carbonate (Equation (1)) <2000S1878>.
OO
OO O
O OMe
O
TBDMS
OO
OO O
OH
TBDMSCl-CO2Me
Pyridine, DCM0 °C, 70 min, then, rt, 40 min70%
ð1Þ
During a nice enantioselective total synthesis of epothilone A using multifunctional asymmetriccatalysis (Suzuki cross-coupling of fragment A with fragment C, followed by Yamaguchi lactoniza-tion), the reaction of the aldehyde with TMS-acetylide affords an alcohol, which is methoxycar-bonylated with methyl chloroformate resulting the carbonate (Equation (2)) <2000JA10521>.
N
S
OTBS
CHON
S
OTBS
O O
Oi. TMS- Li
THF, –78 °C40 min
ii. MeOCOCl
30 min, 79% TMS
_ +
ð2Þ
430 Functions Containing a Carbonyl Group and at Least One Chalcogen
A carbonate intermediate for the synthesis of functionalized ‘‘pyridoindoles,’’ which haveattracted great interest by virtue of their cytotoxic activity toward leukemia cells, has beenprepared by using ethyl chloroformate <2001T4787>. Phenyl chloroformate has been employedin the cyclocarbonylation reaction to prepare an intermediate in synthesis of solanoeclepin A<2000CC1463>.
Functionalization of taxol, which is a powerful anticancer drug, in the position 2, is animportant pharmaceutical tool. This can be achieved advantageously by cyclocarbonylation ofthe 1,2-diol at 13-deoxy-7-TES baccatin III with phosgene yielding 95% of the corresponding1,2-cyclocarbonate (Equation (3)), which will further be reacted with alkyllithium compounds toafford 2-acylbaccatin derivatives under ring opening of the 1,2-cyclocarbonate <1994CC295>.
OH
OH
OAc
OTESAcO O
OH
OH
OAc
OTESAcO O
O O
O
COCl2
Pyridine25 °C, 30 min95%
2 211 ð3Þ
A highly interesting synthetic route for preparing intermediates of ‘‘retinal’’ comprises apalladium-catalyzed transformation of an ‘‘yne-carbonate’’ into an ‘‘allenyl enal.’’ The carbonateis prepared by unsymmetrical carbonylation of propargylic alcohol and silyl enol ether withphosgene, each step with 90% yield (Scheme 1) <1994TL7383>.
In all reactions previously described phosgene is the basic chemical for the preparation ofcarbonates in a direct way as well in the synthesis of the chloroformates. Phosgene itself is apoisonous gas which was discovered in 1812 by Davy from the action of sunlight on carbonmonoxide and chlorine. Extensive safety precautions are required to prevent exposure to phos-gene during handling. In order to avoid the difficulties associated with the toxicity of phosgenegas, equivalents and substitutes for phosgene as well as the ‘‘safety phosgenation’’ have beendeveloped <B-2003MI615-03, 2002EUP1017623, B-1991MI615-01>.
Another often used phosgene equivalent to accomplish carbonylation reactions is the solid1,10-carbonyldiimidazole (CDI). The conversion of (RS)-sec-phenethyl alcohol to its2,2,2-trifluoroethylcarbonate, which is needed for the resolution of ‘‘chiral alcohols,’’ by usingCDI in good yield has been described (Scheme 2) <2000TA1279>.
OH
Ph
COCl2
Ph
O
O
O
TMSO
–CO2
Pd(PPh3)4
Ph
CHO
i. BuLi
ii.
iii.
MeLi
Cat.
90%
90%
Scheme 1
OH O N N
O
O O
O
CF3N
N
N
N
O
CF3 OHCDI
DCM, rt, 2 h98%
10% DMAPDCM, rt, 24 h85%
Scheme 2
Functions Containing a Carbonyl Group and at Least One Chalcogen 431
6.15.1.1.2 Carbonates from carbon oxides and carbonate salts
The bulk chemical diphenyl carbonate (DPhC), which is an important reagent in the manufactureof polycarbonates, has been produced by the oxidative carbonylation of phenol with carbonmonoxide (CO) and air-oxygen catalyzed by Pd dinuclear complexes and redox catalyst(Equation (4)) <1999JMOC(148)289, 2000JMOC(154)243>. Reaction proceeds smoothly on aPd dinuclear complex bridged with a pyridylphosphine ligand [Pd2(Ph2Ppy)2X2] and redoxcatalyst along with ammonium halide in the presence of CO and air at 100 �C and the TOFreaches 19.21 (mol-DPhC/mol-Pd h).
OH
O O
OCO, O22
Pd2(Ph3PPy)2Cl2Redox catalyst
NH4Cl, 100 °C
H2O
DPhC
+ ð4Þ
Dialkylcarbonates have been prepared from CO2 and alkanols under Appel conditions byusing tri-(1-butyl)-phosphane, tetrabromomethane, and cyclohexyl tetramethylguanidine(CyTMG). This strong, hindered, and non-nucleophilic base is more effective than other basessuch as DBU. DMF is the solvent of choice (Equation (5)) <1996CL825>. Yields of dialkylcarbonates derived from various primary alkanols are 54–91%; from secondary alkanols theyare 14–22%.
OR OR
O
2ROH + CO2
+ n-Bu3P
+ CBr4
DMF54–91%
CyTMG+ n-Bu3P=O
+ CHBr3
ð5Þ
A three-component coupling system of aliphatic alcohol/CO2/alkyl halide under a pressureof 160 psig CO2 and in the presence of a peralkylated guanidine has been applied toprepare dialkylcarbonates <1995JOC6205>. Thus, di-1-butylcarbonate is obtained in 73% yield(by GC).
An approach to synthesize ‘‘mixed’’ dialkylcarbonates employs the above three-componentcoupling system aliphatic alcohols/CO2/alkyl halides in the presence of Cs2CO3 and withoutpressure of CO2 (Scheme 3). This method shows a great variety in use of alcohols and alkylhalides (Table 1), reaction times are 2.5–23 h, yields of the resulting mixed dialkylcarbonatesare 91–98% <1999JOC4578>.
One of the most attractive synthetic goals starting from CO2 is the bulk chemical dimethylcar-bonate (DMC). An approach is the organostannane-catalyzed reaction of dehydrated derivativesof methanol (ortho-ester and acetals) with ‘‘supercritical’’ CO2 <1999JA3793, 1998JOC7095,2000POL573>. The reaction of acetals is especially attractive because the starting material ismuch less expensive compared with ortho-esters, and the co-produced acetone can be recycled(Scheme 4).
OHPh
OPh
OBu
O
OPh
OPh
O
O
Cs2CO3
TBAIDMF23 °C, 3.5 h
_Cs
_Cs
CO2
1-BuBr 92%
+ +
Scheme 3
432 Functions Containing a Carbonyl Group and at Least One Chalcogen
6.15.1.1.3 Carbonates from ureas
Processes to produce DMC in high yield are of great interest. There is a need for low-cost DMC,because it becomes more and more important in fuel application as a gasoline additive. DMC hasmany desirable properties: almost 3 times the oxygen content of methyl t-butyl ether (MTBE),good octane for blending (RON of 130), lower volatility than MTBE, and biodegradability.Reaction of methanol with urea to give DMC is a well-known low-yield synthesis, but the useof triethylene glycol dimethyl ether (triglyme) as a solvent, in conjunction with tin catalysts,affords high yields of DMC to be realized (Scheme 5) <1999USP5902894, 1998JAP10259165>.More details on this process are also described in <B-2003MI615-04>.
6.15.1.1.4 Cyclic carbonates and transesterification
Transesterification is used industrially to produce DMC and diethylcarbonate as shown inrecent patents. Dowex MSA 1, CoYO, and Y2O3 are used as catalysts (Equation (6))<1992JAP04198141, 1997JAP09040616, 2001JAP2001316332>.
OOO
MeO OMe
O
Me2Sn(OMe)2
CO2
Supercritical
+2 MeOH
–H2O
cat.+
Scheme 4
NH2 NH2
O
NH2 NH2
O O
OMeMeO
O
OMeMeO
2NH3 + CO2+ H2O
+ 2MeOH + 2NH3
2MeOH + CO2 + H2O
DMC
Diglymetin-cat.
180 °C
98%
Scheme 5
Table 1 Dialkyl carbonate formation using alcohols, halides, and CO2 inthe presence of Cs2CO3
Alcohol (ROH) Halide (R0-X) Time (h) Yield (%)
4-Phenylbutanol t-Butyl 2-bromoacetate 5 95Benzyl chloride 2.5 94Allyl bromide 4 91s-Butyl bromide 23 98n-Butyl bromide 4.5 92
2-Phenylpropanol t-Butyl 2-bromoacetate 5 96Benzyl chloride 3 98n-Butyl bromide 5 96MPMCl 3 92
Source: <1999JOC4578>.
Functions Containing a Carbonyl Group and at Least One Chalcogen 433
OO
OO
OMeMeOOH
OH+ 2MeOH
Cat.+
DMC
ð6Þ
The above-presented process with CoYO as catalyst is also employed in the productionof diphenyl carbonate (DPhC) in 95% yield from ethylene carbonate (EC) (Equation (7))<1997JAP09040616>. It is a continuous process using a fixed bed reactor at 130 �C, a pressureof 9 kg cm�2, and an LHSV of 3 h�1.
OO
O
O
O OOH
OHCat., 130 °C95%
+
i. MeOHii. PhOH
DPhC
ð7Þ
(i) Enzyme catalysis
In a transesterification process by selective alkoxycarbonylation using enzymes in organic solventsas catalysts, the A-Ring precursor of vitamin D3 has been prepared. Candida antarctica lipase(CAL) is found to be the best catalyst in toluene (Equation (8)). Other enzymes are PSL andCVL, other solvents are THF and 1,4-dioxane, yields of alkoxycarbonylation products dependstrongly on conditions and are 17–100%. Regioselective alkoxycarbonylation occurs only at theC-5-(R) hydroxy group <1997JOC4358, 2001JOC4227>.
OHOHO O
N
O
OHOO
O
EnzymeCalToluene
30 °C, 4 h100%
+ð8Þ
Enzymatic acylation in organic solvents has also been employed to synthesize water-solublePaclitaxel derivatives. Thus, potential new ‘‘prodrugs’’ can be generated possessing high solubilityin water. The approach involves an enzymatic acylation of ‘‘paclitaxel’’ with a bifunctionalacylating reagent, catalyzed by enzyme ‘‘thermolysin’’ (from ‘‘bacillus thermoproteolyticusrokko’’) to give an activated carbonate dervative (conversion 83%) <1997JA11554>.
6.15.1.1.5 Acylcarbonates
A detailed review on di-t-butyldicarbonate (BOC2O), a widely used standard reagent for theintroduction of the BOC-group, in its reactions with alcohols in the presence of DMAP is givenby Hassner and Basel <2000JOC6368>. Many general procedures for reactions of BOC2O withcommon alcohols affording O-BOC-derivatives and/or symmetrical carbonates are described(Equation (9)).
RO OBut
O
RO OR
O
O O
O O
ROH +
CarbonatesBOC2O
DMAP
MeCN+
ButBut O ð9Þ
6.15.1.1.6 Carbonates by iodolactonization
An intermediate carbonate 1 for an iodolactonization reaction has been accomplished by usingthe acylcarbonate BOC2O in excellent yield of 98% <1999JOC3798>.
434 Functions Containing a Carbonyl Group and at Least One Chalcogen
OH
O-But
C6H11
O
1
6.15.1.1.7 Polycarbonates
For polycarbonates there is a huge and fast-growing market. They are excellent engineeringthermoplastics and substitutes for metals and glass because of their good impact strength, heatresistance, and transparency, which makes it an ideal material for optical data-storage devices. Anumber of synthetic routes for producing polycarbonates have been described. During thisprocess phenol is removed by distillation and recycled by transesterification with DMC to affordDPhC which is employed again in the polycarbonate production process <1994CBR970,1996PAC367, B-2003MI615-05>.
6.15.1.2 Two Sulfur Functions
6.15.1.2.1 Dithiocarbonates by [3,3]-sigmatropic rearrangement
Alkylxanthate undergoes a thermal [3,3]-sigmatropic rearrangement to form the dithiocarbonate,which is the starting material for a novel rearrangement of allylic thionitrites to thioepoxides(Equation (10)) <2002CC2394>.
SMeS
O
O SMe
S
THF
Reflux, 7 h
R1R2
R1 R2
R3
R3 ð10Þ
6.15.1.2.2 1,3-Dithiol-2-ones by xanthogen disulfide-alkyne cycloaddition
1,3-Dithiol-2-ones (cyclic dithiocarbonates) have been prepared in a single-step synthesis fromdiisopropylxanthogen disulfide and an alkyne in a radical cycloaddition reaction <1995CC1429,1998H2003, 2003OBC129>. The method is versatile and provides good yields; in particular, witharene-substituted alkynes, starting materials are commercially available. The radical cyclization isinitiated by AIBN <1995CC1429> (Scheme 6). The scope of the reaction can be extended tosome alkenes such as bornene and norbornene <1998H2003>.
O
S
SS
S
OO
S
S
R
S
O
R
S
S
S
R
O
CO2Me
MeO
OH
AIBN
Heat2 .
.+
R =
76–82%
** ***
.
Scheme 6
Functions Containing a Carbonyl Group and at Least One Chalcogen 435
This proven method has been applied to the preparation of an intermediate of molybdopterin,where the needed alkynes are disubstituted, yields are similar to those reactions with monosubstitutedalkynes (Equation (11)) <2003OBC129>. For work-up only flash chromatography is necessary.
O
O
N
N H
O
S
SS
S
O
OO
SS
N
N
H
O
+
AIBNToluene
2 x 1.5 h Reflux 77%
ð11Þ
6.15.1.2.3 Mixed methods
Besides these classical methods some less common synthetic approaches have been published.Benzo-1,3-dithiol-2-ones are important precursors for tetrathiofulvalenes (TTFs) which have
been successfully used as building blocks for low-dimensional organic conductors and super-conductors. They have been prepared from benzo-1,3-dithiol-2-thiones (Equation (12))<2003AG(E)2765>. By the same method a 1,3-dithiol-2-one intermediate has been prepared forthe synthesis of a zinc(II) phthalocyanine derivative functionalized with four peripheral substi-tuted TTF units <2002JHC1071>.
S
S
OTBDPS
OTBDPS
SS
S
OTBDPS
OTBDPS
O
Hg(OAc)2
DCM, AcOH 85%
ð12Þ
6.15.1.3 Two Selenium Functions
An unusal synthesis of Se,Se0-diphenyldiselenocarbonate has been accomplished by the reactionof dipotassium nitroacetate with benzeneselenyl bromide in 19% yield (Equation (13))<2001CC1390>. The product is thermally unstable.
KO2C NO2 PhSe SePh
O_K+
+ 2PhSeBrMeOH
1 h, 19%
ð13Þ
6.15.2 CARBONYL CHALCOGENIDES WITH TWO DISSIMILAR CHALCOGENIDEATOM FUNCTIONS
6.15.2.1 Oxygen and Sulfur Functions
6.15.2.1.1 Thiocarbonates from activated carbonates
A simple and efficient procedure has been developed for a one-pot synthesis of substitutedbenzothiazine-2,4-diones from thiosalicylic acid and amines. Both functional groups of thio-salicylic acid are reacted and activated, recpectively, with ethyl chloroformate affording theintermediate thiocarbonate in 62% yield (Scheme 7) <2003H115>.
436 Functions Containing a Carbonyl Group and at Least One Chalcogen
An alkyl chloroformate has also been employed to form thiocarbonates from thiols for the‘‘desymmetrization’’ of 2,20,6,60-tetramethoxybiphenyl by a regioselective sulfenylation reaction<2001TA3313>. This provides an access to C2-symmetric sulfur derivatives. Resolution of2,20,6,60-tetramethoxy-3,30-dimercapto1,10-biphenyl was achieved by conversion to the corre-sponding dithiocarbonate diastereomers.
During the synthesis of potential plant protecting compounds on basis of 2,3-didehydrothiazole-2-thione, isobutyl chloroformate has beenused to acylate the tautomeric formof the thione catalyzed bylead nitrate affording the corresponding thiocarbonate in 89% yield (Equation (14)) <2000JPR554>.
S
NH
S
S
N S OBu
O
But
+ ClCO2Bui
Cat. Pb(NO3)2
DCM, Et3N 89%
But i
ð14Þ
6.15.2.1.2 Thiocarbonates from alkoxycarbonylsulfenyl chlorides
For synthesis of the two conformationally different ‘‘tetrathiacyclododecino tetraindoles’’ theintermediate 3,30-bis(methoxycarbonylsulfenyl)-2,20-biindolyl has been prepared from 2,20-bisindolyl- and methoxycarbonylsulfenyl chloride in excellent yield of 94% (Equation (15))<2002EJO1392>. Reaction occurs at rt within 2 h and needs no Friedel–Crafts catalyst.
NH
NH
NH
NH
S
SO
O
OMe
MeO
MeO2CSCl
DCM, rt, 2 h94%
ð15Þ
6.15.2.1.3 Thiocarbonates from carbonothioic acid salts
As described above, S-methyl O-benzyl carbonothioates with substituted phenyl groups have beenprepared by carbonylation of benzyl alcohols with carbon monoxide and sulfur (or carbonylsulfide) in the presence of DBU followed by esterification using methyl iodide in good yields(Equation (16)) <2002T10011>.
SH
CO2H
S
O
O
O
OEt
O OEtNH2
S
O
O OEt
NH
+ 2ClCO2Et
62%
+ CO2 + EtOH
CHCl3
2Et3N
Scheme 7
Functions Containing a Carbonyl Group and at Least One Chalcogen 437
OH O S
O
+ CO + S
i. DBU, THF 1 MPa CO 80 °C, 6 h
ii. MeI 20 °C, 16 h 89%
ð16Þ
6.15.2.1.4 Other methods
Benzimidazo[1,2-c]quinazoline-6(5H)-thiones were prepared by cyclization of 1,2-diaminobenzenewith dimethyl 2-isothiocyanatoterephthalate and acylated with ethyl chloroformate according toEquation (17) affording thiocarbonate in 70% yield <2002MI615-01>.
NH2
NH2
N=C=S
CO2Me
MeO2C N
N
NS
CO2Me
OOEt
+i. PriOH
ii. ClCO2Et DMF, Et3N 70%
ð17Þ
A convenient process for the synthesis of highly functionalized glyoxylic acid derivatives hasbeen accomplished by reaction of n-butylglyoxylate with triphosgene, sodium thioethylate, andbenzoic acid, to provide the acetal containing a thiocarbonate moiety with excellent yield of 91%(Equation (18)) <2002S365>.
BunO
O
O
BunOO
O
O
O
Ph
SEtOi. (Cl3CO)2CO THF, pyridineii. NaSEt, Et2O
iii. Ph-CO2H THF, DIPEA 91%
ð18Þ
According to Equation (19) a thiocarbonate is quantitatively formed from methyl 2-thioxo-3H-benzoxazole-3-carboxylate with 1,6-dimethyl-2,4-hexadiene in a photochemical reaction<2002HCA2383>.
O
N
O
OMe
SO
NS
O
OMe
Photochem.Benzene, 100%
ð19Þ
6.15.2.2 Other Dissimilar Chalcogenide Functions
6.15.2.2.1 Oxygen and selenium functions
During the synthesis of ‘‘mucocin,’’ a powerful antitumor ‘‘acetogenin,’’ the 4-hydroxybutenolideterminus is a key intermediate. Its precursor, the selenocarbonate, has been prepared according toScheme 8 in a yield of 89% <1998TL9627>. Total synthesis of mucocin was achieved in ananalogous way for preparing the selenocarbonate 2 (yield 78%) by using TBDPS protective groupand triphosgene instead of phosgene as a carbonyl source <2002JOC5739>. In the synthesis of‘‘(+)-juruenolide C,’’ a 5-exo-digonal radical cyclization has been applied with a selenocarbonateintermediate 3, which has been prepared in 74% yield in a similar way as described above byusing carbonyldiimidazole (CDI) as a carbonyl source <2001JOC4841>.
438 Functions Containing a Carbonyl Group and at Least One Chalcogen
TBDPSO
O O
O Se
O
OMeMeO
Ph
TBDPS = t-butyl diphenyl silyl
2
O
OO
Bu2SiH
OSe
O
Ph
3t
Preparation of 5-selenopentopyranose sugars from pentose starting materials by samarium(II)iodide or (phenylseleno)formate-mediated ring closures is described <2000T3995>. Selenocarbo-nates have been prepared by insertion of selenium into the zinc–carbon bond of arylzinc halidesforming corresponding zinc selenoates which react with acyl halides in the presence of HMPAproviding selenocarbonates in good yields (Equation (20)) <2002MI615-02>.
MgBr Se
O
OMei. ZnCl2, THFii. Se
iii. ClCO2Me HMPT 70%
ð20Þ
6.15.2.2.2 Oxygen and tellurium functions
Alkyl aryl tellurocarbonates, which are effective precursors of oxyacyl, primary, and secondaryalkyl radicals, have been prepared from diphenyl ditelluride and alkyl chloroformate in goodyields (Equation (21)) <1996JOC5754>. The same tellurocarbonates can be obtained in yields of60–96% by palladium-mediated reactions of chloroformates with aryltellurotris(trimethylsilyl)-silane (Equation (22)) <1998JOC5713>.
THF, 91%
TeTePh
PhTe
O
MeOPh
i. NaBH4
MeOH, THF
ii. ClCO2Með21Þ
TBDMSO
O
TBDMSO
OH
Cl Cl
O
TBDMSO
O Cl
O
TBDMSO
O Se
O
Ph
+
BuLi THF
TBDMS = t-butyl dimethyl silyl
Et3N
PhSeHPyridine
89%
Scheme 8
Functions Containing a Carbonyl Group and at Least One Chalcogen 439
SiMe3 Si Te
SiMe3
SiMe3
PhTe
O
MeOPh+ ClCO2Me
Pd(PPh3)4
Benzene80%
ð22Þ
6.15.2.2.3 Sulfur and selenium functions
A thioselenocarbonate precursor for the synthesis of thioselenofulvalenes, which are strongelectron donors, has been prepared in several steps according to the overall Equation (23)<2002JOC4218>.
O
O
I
Cl-Mg
S
S
Se
SO
KCNS + + + Se + EtSCN + CS2 + Tol-SO2Cl
83%ð23Þ
6.15.3 CARBONYL CHALCOGENIDES WITH A CHALCOGEN FUNCTIONAND ONE OTHER HETEROATOM FUNCTION
6.15.3.1 Oxygen and Nitrogen Functions
Carbamates are carbonic acid derivatives containing a carbonyl function directly connected to an alkoxyfunction and an amino function. They are important for producing pharmaceuticals and polymers, andtherefore many preparative methods exist. A review is given in <B-2003MI615-06>.
The formal constitution allows a great deal of variety in the alkoxy component as well as thebasic amino function. In general, two synthetic approaches to carbamates can be distinguished:the first method involves a carbonic acid derivative of an alcohol or of a phenol reacting withammonia or amine and the second one involves carbonic acid derivatives of ammonia or anamine reacting with an alcohol or a phenol.
6.15.3.1.1 Carbamates from chloroformates or phosgene equivalents
Chloroformates are easily prepared using phosgene or phosgene equivalents <B-2003MI615-07> suchas the readily available triphosgene (bis(trichloromethyl)carbonate) <1987AG(E)894, 1996S553>.
2-Methyl-2-propyl-1,3-propanediol dicarbamate (Meprobamate), a general sedative, issynthesized by the low-temperature phosgenation of the substituted 1,3-propanediol in aninert medium in the presence of a tertiary amine, followed by conversion of the bischlorofor-mate derivative to the dicarbamate by ammoniation with gaseous NH3. Antipyrine gaveconsistently higher yields than other tertiary amines (Equation (24)) <B-2001MI615-01,1951JA5779>.
OH OHO OH2N NH2
OO
i. COCl2 Antipyrine Toluene, CHCl3
ii. NH3 (g)
ð24Þ
2-Cyclohexenyloxycarbonyl chloride has been reacted with 2-hydroxymethylaniline to providethe corresponding carbamate in 76% yield (Equation (25)) <1999AG(E)1928>.
440 Functions Containing a Carbonyl Group and at Least One Chalcogen
O
O
ClH
NH2
OHNH
OH
O OH
+
PyridineDCM
0 °C to rt2 h, 76%
ð25Þ
(4R,5S)-4,5-diphenyl-2-oxazolidinone has been prepared from (1S,2R)-(+)-2-amino-1,2-diphenylethanol and triphosgene (Equation (26)) <1998OS45>. It is used for the synthesisof optically active amines because of its high stereoselectivity and easy deprotection by hydro-genolysis after the reaction <1993TL289>. The procedure can also be used for preparing2-oxazolidinones from various 2-aminoethanol derivatives.
OH
NH2
Ph
Ph NH
OO
Ph
PhO
OCCl3Cl3CO
DCMEt3N
<10 °C, 3 h 99%
+ ð26Þ
Triphosgene (1/3 equivalent) has also been employed advantageously in the preparation of6-methoxy-2-oxo-2,3-dihydrobenzoxazole (MBOA), in yield of 75%, from 2-amino-5-methoxy-phenol (Equation (27)) <1989S875>. With the exception of CDI, approaches by using otherreagents—such as phosgene, urea, or potassium cyanate—employed in the reaction providesubstantially lower yields of MBOA <B-2003MI615-08>.
OH
NH2
MeO0.33 equiv. (Cl3CO)2CO MeO
NH
OO
2 equiv. Et3N THF, rt30 min, 75%
ð27Þ
6.15.3.1.2 Carbamates from isocyanates
Highly functionalized carbamate intermediates suitable for potential elaboration to ‘‘esperamici-none’’ have been prepared by Nicolaou employing phenyl isocyanate to react with an epoxyalco-hol in excellent yield (99%) (Equation (28)) <1994T11391>. O-benzyl N-vinyl carbamate hasbeen prepared from vinyl isocyanate and benzyl alcohol <2002OPRD74>.
OO
OO OTBDMS
O
HN
PhO
OO
OOH OTBDMS
OPh-N=C=O
DCM, Et3N25 °C, 1 h 99%
TBDMS = ButMe2Si
ð28Þ
The first ‘‘molecular motor,’’ which consists of just ‘‘78 atoms,’’ was developed by Kelly andgets rotational energy from forming a cyclic carbamate which causes a directed movement of therotor as shown in Scheme 9. The carbamate results from the addition reaction of the iso-cyanate (at the rotor) with the alcohol function (connected over a propoxy linker to the baseplate) <2000JA6935, 1999NAT(401)150>.
6.15.3.1.3 Carbamates from N,N0-carbonyldiimidazole (CDI)
CDI is widely used in the preparation of oxazolidinones. It has been employed in the synthesisof (4S,5R)-5-[(E)-dec-1-en-1-yl]-4-methyl-2-oxazolidinone (Equation (29)) <1999JOC6147,1992JOC5469>. Further similar applications of CDI on oxazolidinones are given <2000T8643,1998S627>.
Functions Containing a Carbonyl Group and at Least One Chalcogen 441
HN O
O
C8H17
H2N OH
C8H17
THF, 20 °C2 h, 70%
NN N
N
O
ð29Þ
An elegant method for formation of N-imidazole carbamates is the reaction of alcohols withCDI which in this case is an aminocarbonylating reagent. Thus, 2,6-dimethylphenol has beenreacted with CDI to result in the formation of the carbamate in good yield of 91% (Equation(30)) <2002S29>.
OH
Me
Me
DCM, reflux5 h, 91%
O
Me
MeN
O
NCDIð30Þ
6.15.3.1.4 Carbamates from carbonates or dicarbonates
Diethylcarbonate is employed for the cyclocarbamation of various aminoalcohols. The reaction iscatalyzed by basic substances, such as sodium methoxide, magnesium methoxide, potassiumhydroxide, or sodium or potassium carbonate. Sodium methylate in xylene <1996S719>, potas-sium or sodium carbonate under reflux <1993TA2513, 1999EJO2965> are the preferred reactionconditions. The reaction has wide scope and synthetic utility. 4,4-Dimethyl-2-oxazolidone hasbeen prepared with diethylcarbonate in excellent yield (98%) (Equation (31)) <1991T2801>.
OH
NH2
H3C
H3C
(EtO)2CO
NH
OH3C
H3C
OK2CO3, 120 °C2 h, 98%
ð31Þ
Preparation of t-butyl carbamates with BOC2O from amines (and their one-pot conversion toamides with acyl halide–methanol mixture) in mostly quantitative yields has been described(Equation (32)) <2002S203>. A review on reactions of BOC2O with amines forming carbamateshas appeared <2000JOC6368>.
NH2
BOC2ONH
R1O
OBut
R1
R1 = PhCH2 (92%)
n-C8H17 (100%)PriOC(O)CH2 (100%)
BOC = ButOCO
ð32Þ
N
Me
O
Me
O
O O
N
Me
ON
OO
Rotationover Eact–25 kcal
O
H
H
rotor Baseplate
OHC
Scheme 9
442 Functions Containing a Carbonyl Group and at Least One Chalcogen
t-Butoxycarbonylation of an amidic nitrogen with BOC2O, in acetonitrile at room temperature,as part of an efficient and regioselective method for the exchange of the N-benzoyl group inPaclitaxel (Taxol1) 4 to 10-acetyldocetaxel and to Docetaxel 5 has been reported (Equation (33))<1999TL189>. Paclitaxel1 4 and its semisynthetic analog Docetaxel (Taxotere1) 5 are amongthe most important new antitumoral agents of the 1990s.
R2O OH
OOHO
HAcOOPh
O
OH
NHR1
OO
COPh
4 Paclitaxel R1 = Ph, R2
= Ac5 Docetaxel R1
= But O, R2 = H
AcO OSiEt3
OOHO
HAcOOPh
O
O
NHPh
OO
COPhOBn
O
AcO OSiEt3
OO O
HAcOOPh
O
O
NPh
OO
OBn
O
COOtBu
BOC2O, DMAP
MeCN, rt, 24 h61%
Ph OtBu
ð33Þ
6.15.3.1.5 Carbamates from carbon oxides
Carbamates can be obtained from carbon monoxide (CO) or carbon dioxide (CO2) as outlined in<B-2003MI615-09>. A review on converting carbon dioxide into carbamato derivatives has beenreported treating mainly carbamato metal complexes and their reactions <2003CRV3857>.
Carbon dioxide (CO2) can be reacted with amines and alkyl halides in the presence of bases(Scheme 10) <1995JOC2820>. Use of sterically hindered guanidine bases gives best results,i.e., 80–99% yield with virtually 100% selectivity. But the need for stoichiometric amounts ofbase causes serious limitation to the large-scale application of the process.
The transformation of vicinal aminoalcohols with CO2 to the corresponding carbamates in acatalytic process that occurs in good yields has been described (Equation (34)) <2002SL307>.The catalyst is commercially available n-Bu2SnO in powder form, which is stable in air.
R1HN OH
R2 R3
N
OO
R3
R2
R1
R1 = Me, R2
= R3 = H, 94%R1
= Et, R2 = R3
= H, 76%R1
= R2 = R3
= H, 53%R1
= R2 = H, R3
= Me, 73%R1
= H, R2 = R3
= Me, 85%
NMP180 °C, 16 h
+ CO2
10 mol.%nBu2SnO
ð34Þ
R1HN R1HNO
O
O
O
R1NH2 + CO2
Guanidine _
GuanidineH+
Hal-R2
R2 + GuanidineHHal
Scheme 10
Functions Containing a Carbonyl Group and at Least One Chalcogen 443
6.15.3.1.6 Carbazates
Generally carbazates can be divided into two groups: monoacylated and bisacylated derivatives.They are obtained simply by reacting alkyl- or aryl chloroformates with hydrazine hydrate, orwith alkyl- or arylhydrazine derivatives. Chloroformate as an intermediate is employed in thereaction of 3-chlorophenol, diphosgene, and hydrazine (Equation (35)) <1998CCC793>.
Cl OH Cl O NH
NH2
O
i. Cl3COCO–Cl
ii. N2H4, Et2O88%
ð35Þ
Instead of chloroformates, unsymmetrically substituted O-alkyl O0-phenylcarbonates can beused; the phenoxy group activates the carbonate ester <1968HCA622, 1984CJC574> (Equation(36)). In special cases, dialkylcarbonates, particularly the symmetrical ones, have been employedto achieve carbazates in good yields (Equation (37)) <2002CJC1187, 2000GEP19837070>.
OO
O
PhO
NH
O
NH2
H2NNH2ð36Þ
O O
O
PhOH O N
H
NH2
OPhH2NNH2
DCM77%
ð37Þ
6.15.3.1.7 Azidoformates
The chloroformates to be used for the synthesis of azidoformates can be generated in situ from analcohol and phosgene <1991JCS(P1)37> or a phosgene equivalent such as diphosgene<2001JOC6585> or triphosgene <2003T8233, 2002SL1455>. A synthesis of fused 2-pyrrolinesvia thermolysis of 6-substituted 3,5-hexadienylazidoformates is described <2001JOC6585>.During a total synthesis of a penicillin N analog the intermediate azidoformate has been preparedby using triphosgene as shown in Equation (38) <2003T8233>.
OH
S
H CO2EtO
S
H CO2EtO
N3
i. (Cl3CO)2CO Pyridine CCl4, 50 °C
ii. NaN3, DMF50 °C, 67%
ð38Þ
6.15.3.2 Oxygen and Phosphorus Functions
6.15.3.2.1 Phosphinecarboxylates by the Arbuzov reaction and related methods
Alkyldialkyloxyphosphinecarboxylate oxides are prepared by reacting alkyl chloroformates andtrialkyl phosphites in a typical Arbuzov reaction (Equation (39)) <1998T12233>.
Cl
O
OEt P
O
EtOEtO
O
OEt(EtO)3P +91%
+ EtCl ð39Þ
Alkoxycarbonyl-substituted t-butylmethylboranes have been synthesized from the reaction oft-butylphosphine with an alkyl chloroformate, methyl iodide, and borane/THF in yields of 61–85%(Equation (40))<2002BCJ1359>. Also disubstituted derivatives have been prepared in yields of 86–99%.
444 Functions Containing a Carbonyl Group and at Least One Chalcogen
Cl
O
O
P
O
OH3B
But-PH2 + BH3-THF + MeI +
BuLi, THFHexane
67%
But
ð40Þ
6.15.3.3 Oxygen and Other Heteroatom Functions
6.15.3.3.1 Oxygen and boron functions
Tricyclohexylphosphine(methoxycarbonyl)borane has been prepared from the reaction tricyclohexyl-phosphine-iodoborane with DMC as carboxylating reagent (Equation (41)) <2000JA6329>.
B
H
H I B
H
BrO
OMe
c-Hex3 P
+ Me2CO3
(i)
i. (p-But-C6H4)2*Li TMEDA, THF
ii. Br2, MeOH
c-Hex3 P
ð41Þ
As a synthon for novel ‘‘carboranyl peptides,’’ water-soluble icosahedral carboranyl anionshave been synthesized by the above methods <2002CCC1095>.
6.15.3.4 Sulfur and Nitrogen Functions
6.15.3.4.1 Thiocarbamates from chlorothioformates and amines
A simple and efficient procedure has been developed for a one-pot synthesis of benzothiazine-2,4-diones directly from thiosalicylic acid and amines; the reagent for supply of the carbonylgroup is ethyl chloroformate (Equation (42)) <2003H115>.
SH
CO2H
Cl
O
OEt
NH2
S
N
O
O
Ph+ +
CHCl3
Et3N66%
ð42Þ
6.15.3.4.2 Thiocarbamates from carbamoyl chlorides and thiols
A synthesis of S-2-cyclohexenyl N-dialkyl thiocarbamates is described (Equation (43))<2002OL4217>.
SH
Cl Ni-Pr2
Ni-Pr2O
O
S
+i. NaH, THF
ii. H2O, 82% ð43Þ
Thiocarbamates can also be prepared from carbamoyl chlorides and disulfides which arereductively acylated in the presence of Yb metal and a catalytic amount of MeI (Equation (44))<2002JCR(S)442>.
Functions Containing a Carbonyl Group and at Least One Chalcogen 445
N
N
S
O
O
O
Cl
O
S
S
Br
Br
N
N
S
O
O
O
S
O
Br
+
YbCat. MeI
HMPTTHF83%
ð44Þ
6.15.3.4.3 Thiocarbamates from isothiocyanates and alcohols
An example for the synthesis of a thiocarbamate by reaction of an isothiocyanate with an alcoholis given <2002JGU1146>. The primary generated thioncarbamate undergoes thione–thiol(Newman–Kwast) rearrangement providing the thiocarbamate. According to Scheme 11 thisimmediately reacts intramolecularly to afford the 4-phospha-1,3-thiazolidin-2-one.
6.15.3.4.4 Thiocarbamates from alkylamide salts, carbon monoxide, and sulfur
1,3-Thiazolidin-2-one has been prepared from 2-aminoethanethiol, elemental sulfur, and carbonmonoxide in good yield of 87% (Equation (45)) <2002T7805>.
NH2
SH
S
NH
O+ CO
S8, K2CO3
DMF, O2
87%
ð45Þ
6.15.3.4.5 Thiocarbamates from [3,3]-sigmatropic rearrangement
2-Cyclohexenol reacts with methyl isothiocyanate via Newman–Kwast rearrangement to formS-2-cyclohexenyl N-methyl thiocarbamate (Equation (46)) <2002EJO2970>.
OH S NHMe
O+ Me-N=C=S
i. NaH, THF
ii. NaHCO3
H2O, 80%
ð46Þ
A series of isothiocyanate-substituted allenes has been prepared by [3,3]-sigmatropic rearrange-ment of the corresponding propargyl thiocyanates. Further reaction of the isothiocyanate allenesprovides a substituted 1,3-thiazolin-2-ones; an example is given in Equation (47) <2002S1423>.
S=C=N
S=C=N
S
NH
Et
OMe
O
MeOHH2O
32%ð47Þ
S=C=N P
S
OPh
ClS
PNH
S
OPh
ONH
PS
OPh
Cl
S
OEt
NH
PS
OPh
Cl
O
SEt
EtOH
–EtCl
Rearr. 27%
Scheme 11
446 Functions Containing a Carbonyl Group and at Least One Chalcogen
6.15.3.4.6 Thiocarbamates from trichloroacetyl chloride, thiols, and amines
It has been found that the carbonyl group in trichloroacetic acid esters behaves like one incarbonic acid ester, i.e., it can be reacted twice with nucleophiles. This is exploited for a simpletwo-step synthesis of thiocarbamates from trichloroacetyl chloride, thiol, and amine<2003JOC3733>. Either trichloroacetyl chloride can be reacted first with an amine and thenwith a thiol, or first with a thiol and then with an amine (Scheme 12). The latter methodprovides significantly better yields of 83–100% for thiocarbamates.
6.15.3.5 Sulfur and Phosphorus Functions
6.15.3.5.1 Phosphonothioformates
Trialkylphosphonothioformates have been prepared in a mild one-pot reaction by sequentialreaction of phosgene with alkanethiols, and subsequent Arbuzov reaction with trialkyl phosphitesin good yields (Equation (48)) <2000SL815>.
Cl Cl
O
S
O
P(OEt)2
O
i. Toluene n-PrSH Et3N, DCM
ii. P(OEt)3
Toluene 84%
+ EtCl ð48Þ
6.15.3.6 Other Mixed Systems
6.15.3.6.1 Selenium and nitrogen functions
A ring-closure reaction has been performed using elemental selenium, carbon monoxide, andalkyl(prop-2-ynyl)amines resulting 5-alkylideneselenazolin-2-ones stereoselectively via cycloaddi-tion of the in situ generated carbamoselenoates to the carbon–carbon triple bond<2002JOC6275>. Yields are 58–95% of product (Equation (49)). Butyl(but-3-ynyl)amine affordsthe corresponding six-membered selenium-containing heterocycle (69% yield) with the aid of CuI<2002JOC6275>.
NHR
NSe
O
RSe + CO +
i. DBU, THF rt, 1.5 h
ii. Sat. NH4Claq
rt, 5 min
R
Me 78Pri
Bu 95c-Hex 76
Productyield (%)
58ð49Þ
S CCl3
O
CCl3
O
NEt2
S N
O
R1-SHCl3CCOCl R1
Et2NHCl3CCOCl
R1R2
R3
HNR2R3
R -SH1
83–100%
54–63%
R1 = n-Hex, Ph, p-ClBn
R2 = H, Et
R3 = H, Et, But
Scheme 12
Functions Containing a Carbonyl Group and at Least One Chalcogen 447
Also N-heterocyclic carbamoyl chlorides have been employed in the synthesis of carbamates.Thus, N-(phenylselenocarbonyl)oxazolidin-2-one has been prepared with 85% yield by treatmentof the Li salt of oxazolidinone with triphosgene, followed by addition of PhSeH <1999SL1657>(Scheme 13).
The samarium-iodide-mediated reaction of N-chlorocarbonyl-imidazolidin-2-one-N0-methan-solfonamide with dinaphthyl diselenide provides the corresponding naphthylselenocarbamate in82% yield via the samarium selenolate RSeSmI2 <2002JCR(S)168> (Equation (50)).
NN
O
SOO O
ClSe
Se NN
O
SOO O
Se+
SmI2THF
82%
ð50Þ
An easy access to benzoselenazine-2,4-diones has been described <1995AJC1221>.N-butylbenzamide has been reacted with dibenzyl diselenide to provide 2-benzylseleno(butyl)-benzamide, which has been treated with trimethylsilyl triflate. Resulting N-TMS-benzamide isfurther reacted with phosgene to afford 3-butyl-2H-1,3-benzoselenazin-2,4(3H)-dione in 80%yield (Scheme 14).
A rather exceptional access to selenocarbamates with potential antiviral properties is thetreatment of an isocyanate with LiAlHSeH and the alkylation of the resulting selenide by analkyl halide <2002JOC486>. Thus, Se-methyl N-phenylselenocarbamate has been prepared in70% yield (Equation (51)).
N=C=OPh
NH
Se–Me
O
Ph
i. LiAlHSeH THF, rt, 1 h
ii. MeI, rt, 2 h 70%
ð51Þ
O
NH
O
O
N O
O Cl
O
N O
O SePh
i. BuLi
ii. (Cl3CO)2C=O
PhSeHPyridine
85%
Scheme 13
NH
O
NH
O
Se
N
O
SeSe
N
O
O
i. BuLi
ii. (BnSe)2 Bn
TMS-Tf
Bn
TMS
rt, overnight
COCl2rt, 12 h
80%
Scheme 14
448 Functions Containing a Carbonyl Group and at Least One Chalcogen
6.15.3.6.2 Tellurium and nitrogen functions
A method using very simple starting materials for the preparation of tellurocarbamates employselemental tellurium and carbon monoxide together with amines and alkyl halides<1993HAC471>. Thereby the corresponding lithium amides react with tellurium under atmo-spheric pressure of carbon monoxide to yield carbamotellurates, which are trapped with alkylhalides to obtain the tellurocarbamates (Scheme 15). Satisfactory yields of above 60% can onlybe achieved, if the correct order of reaction steps is maintained
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NH NLi N
O
TeBuLi
THF–78 °C
i. Teii. CO (1 atm), 2 hiii. EtBr, 1 h
THF–78 °C 65%
Scheme 15
Functions Containing a Carbonyl Group and at Least One Chalcogen 449
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2002EJO2970 F. Marr, R. Frohlich, B. Wibbeling, C. Diedrich, D. Hoppe, Eur. J. Org. Chem. 2002, 2970–2988.2002EUP1017623 H. Eckert, B. Gruber, N. Dirsch, Eur. pat. 1017623 (2002) (Chem. Abstr. 1999, 130, 211406).2002HCA2383 T. Nishio, K. Shiwa, M. Sakamoto, Helv. Chim. Acta 2002, 85, 2383–2393.2002JCR(S)168 W. Su, N. Gao, Y. Zhang, J. Chem. Res. (S) 2002, 168–169.2002JCR(S)442 W. Su, N. Gao, V. Zhang, J. Zhu, J. Chem. Res. (S) 2002, 442–443.2002JGU1146 N. A. Khailova, R. Kh. Bagautdinova, M. A. Pudovik, T. A. Zyablikova, N. M. Azancheev,
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4218–4227.2002JOC5739 S. Takahashi, T. Nakata, J. Org. Chem. 2002, 67, 5739–5752.2002JOC6275 S.-i. Fujiwara, Y. Shikano, T. Shin-ike, N. Kambe, N. Sonoda, J. Org. Chem. 2002, 67, 6275–6278.2002MI615-01 A. Ivachtchenko, S. Kovalenko, O. Drushlyak, Heterocyclic Comm. 2002, 8, 233–236.2002MI615-02 X. H. Xu, W. Q. Liu, Chin. Chem. Lett. 2002, 13, 283–284.2002OL4217 F. Marr, D. Hoppe, Org. Lett. 2002, 4, 4217–4220.2002OPRD74 C. K. Govindan, Org. Proc. Res. Dev. 2002, 6, 74–77.2002S29 W. Fischer, Synthesis 2002, 29–30.2002S203 A. Nazih, D. Heissler, Synthesis 2002, 203–206.2002S365 M. J. Mulvihill, J. Gallagher, B. S. MacDougall, D. G. Weaver, D. V. Nguyen, K. H. Chung,
W. Mathis, Synthesis 2002, 365–370.2002S1423 K. Banert, S. Groth, H. Huckstadt, J. Lehmann, J. Schlott, K. Vrobel, Synthesis 2002, 1423–1433.2002SL307 K. Tominaga, Y. Sasaki, Synlett 2002, 307–309.2002SL1455 R. Patil, G. Parveen, V. K. Gumaste, B. M. Bhawal, Synlett 2002, 1455–1458.2002T7805 T. Mizuno, J. Takahashi, A. Ogawa, Tetrahedron 2002, 58, 7805–7808.
450 Functions Containing a Carbonyl Group and at Least One Chalcogen
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Tetrahedron 2003, 59, 8233–8243.
Functions Containing a Carbonyl Group and at Least One Chalcogen 451
Biographical sketch
Heiner Eckert was born in Munich, Germany, where he did his diplomain chemistry at the Technical University of Munich (TUM) in 1973, andreceived his Ph.D. with ‘‘summa cum laude’’ under Prof. Ugi three yearslater. In 1977 he founded ‘‘Dr. Eckert GmbH,’’ a company specializingin developing fine chemicals and processes for chemical production(phosgenations). At present he is working as an Academic Director atthe TUM, with his research focused on new methods in organic synth-eses development. Dr. Eckert has published numerous scientific papersand patents (natural product syntheses, metal phthalocyanines asreagents and catalysts), and indeed the ‘‘Eckert hydrogenation catalysts’’are named after him. In 2003, he published the voluminous book Phos-genations–A Handbook.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 429–452
452 Functions Containing a Carbonyl Group and at Least One Chalcogen
6.16
Functions Containing a Carbonyl
Group and Two Heteroatoms Other
Than a Halogen or Chalcogen
O. V. DENISKO
Chemical Abstracts Service, Columbus, OH, USA
6.16.1 FUNCTIONS CONTAINING AT LEAST ONE NITROGEN FUNCTION (AND NOHALOGENS OR CHALCOGENS) 454
6.16.1.1 Carbonyl Derivatives with Two Nitrogen Functions 4546.16.1.1.1 Reactions with isocyanates 4546.16.1.1.2 Reactions with metal cyanates 4606.16.1.1.3 Carbonylation of amines 4606.16.1.1.4 Substitution reactions of amines with phosgene and its equivalents 4616.16.1.1.5 Oxidation of thioureas and related compounds 4666.16.1.1.6 Reactions of amines with amides and other carboxylic acid derivatives 4666.16.1.1.7 Miscellaneous reactions 4676.16.1.1.8 Preparation of carbamoyl azides 468
6.16.1.2 Carbonyl Derivatives with One Nitrogen and One P, As, Sb or Bi Function 4686.16.1.2.1 Carbonyl derivatives with one nitrogen and one phosphorus(III) function 4686.16.1.2.2 Carbonyl derivatives with one nitrogen and one phosphorus(V) function 4696.16.1.2.3 Carbonyl derivatives with one nitrogen and one arsenic function (carbamoyl arsines) 4706.16.1.2.4 Carbonyl derivatives with one nitrogen and one antimony function 4716.16.1.2.5 Carbonyl derivatives with one nitrogen and one bismuth function 471
6.16.1.3 Carbonyl Derivatives with One Nitrogen and One Metalloid (B, Si, Ge) Function 4716.16.1.3.1 Carbonyl derivatives with one nitrogen and one boron function 4716.16.1.3.2 Carbonyl derivatives with one nitrogen function and one silicon function (carbamoyl silanes) 4726.16.1.3.3 Carbonyl derivatives with one nitrogen and one germanium function (carbamoyl germanes) 473
6.16.1.4 Carbonyl Derivatives with One Nitrogen and One Metal Function 4736.16.1.4.1 Carbon monoxide insertion reactions 4736.16.1.4.2 Aminative carbonylation 4746.16.1.4.3 Amination 4746.16.1.4.4 Reactions with heterocumulenes (isocyanates, ketenimines, azides, carbodiimides) 4756.16.1.4.5 Miscellaneous reactions 476
6.16.2 FUNCTIONS CONTAINING AT LEAST ONE PHOSPHORUS, ARSENIC, ANTIMONY,OR BISMUTH FUNCTION (AND NO HALOGEN, CHALCOGEN, OR NITROGENFUNCTIONS) 476
6.16.2.1 Carbonyl Derivatives with Two P, As, Sb, or Bi Functions 4766.16.2.2 Carbonyl Derivatives with One Phosphorus and One Metal Function 4786.16.2.3 Carbonyl Derivatives with One B, As, Sb, or Bi Function, and One Metal Function 479
6.16.3 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION (ANDNO HALOGEN, CHALCOGEN, OR GROUP 5 ELEMENT FUNCTIONS) 479
6.16.3.1 Carbonyl Derivatives with Two Silicon Functions 4796.16.3.2 Other Carbonyl Derivatives with Two Metalloid Functions 4806.16.3.3 Carbonyl Derivatives with One Metalloid and One Metal Function 480
6.16.4 CARBONYL DERIVATIVES CONTAINING TWO METAL FUNCTIONS 481
453
6.16.1 FUNCTIONS CONTAINING AT LEAST ONE NITROGEN FUNCTION (AND NOHALOGENS OR CHALCOGENS)
6.16.1.1 Carbonyl Derivatives with Two Nitrogen Functions
6.16.1.1.1 Reactions with isocyanates
(i) Additions of amines to isocyanates with formation of acyclic ureas
(a) Starting materials. The addition of various amines to isocyanates (Equation (1)) representsthe most widely used approach to the preparation of mono-, di-, and trisubstituted ureas and theirfunctionalized derivatives, especially if the starting isocyanates are readily available.
N C OR1
N N
O
R1
H
R2
R3+ R2R3NH ð1Þ
As an amine component, ammonia <1994S56>, primary aliphatic amines <1999JOC2835,2001MI351, 2003TL2065>, secondary aliphatic amines <2002PS(177)1303> and their silylated<1996JGU349> and labeled <1993MI655> analogs, cycloalkyl <2001JCO171> and cycloalk-enylamines <2001CPB391>, polyaza macrocycles <2001EJO1943>, hydroxyalkyl amines<2001JMC2344, 2001MI191>, N-hydroxylamines <2000MI115723> and their O-alkyl deriva-tives <1992BAU1920, 1996TL5835>, amino acids <1997TL4603, 2000TL1487>, allylic amines<1993SC2065>, benzylic amines <1998TL1121, 1999JOC2835, 2000PHA490, 2003TL2065>,arylamines <1996JMC1243, 1997SL1184, 1999JOC2835, 2003MI425>, heteroaryl amines<1995JHC13, 2000BAU1202, 2001CPB391, 2001JCS(P1)2012, 2002CPB1379, 2002JMC2994>,heterocyclic saturated <1996SC3685, 1997HCA966, 1998JCS(P1)3127, 2002HCA2458> andpartially hydrogenated amines <1992JHC1189, 2003SC1449>, azaheteroaromatics<1995SL605>, heterocyclic ammonium and aminophosphonium salts <1993H(35)1237,1994JOC7144, 2002JOC5527>, aminophosphonates <1993PS(85)161, 1994OPP357,2002PS(177)1303>, diamines <2001PHA361, 2002MI81, 2002ZN(B)937, 2003JMC1112>, poly-amines <1995CL759>, amino-substituted calixarenes <1995JOC6448, 2000MI1152,2002T7207>, steroidal amines <2002OL4639>, amino sugars <1993T2655, 1993T2676,2002SL1779>, nucleosides <1995BSB411>, amino borabicyclononanes <1992HAC245>, cyanoimines <2002JOC5546>, sulfimines <1999H(51)2035>, metalated acrylamides <2001JGU1953>,N-arylsulfonyl sulfenamides <2001JOU1611>, sulfonamides <1994AP819, 1998EUP879816,2001MI127, 2001MI404>, hydrazines <1994H(38)235, 1994JOC6487, 1996SC2941,2001JMC1475, 2001MI42>, N-amino indoles <2001SL222>, hydrazides <1994AP469,2000PHA490, 2001JMC1475, 2001MI180>, carbamates <1999TL6545>, isoureas<1995AP393>, isothioureas <1996TL1945, 2002JCO285>, thiourethanes <1992JOU1635>,guanidines <2002H(57)1799>, triazenes <2000JCO710>, and even amino ligands of organome-tallic complexes <1994JOM(465)297> were used successfully.
Along with amines, isocyanates could also be used to introduce one or more functional groupsin the urea molecule. Due to the mild reaction conditions generally used, the reaction is tolerantto a wide variety of functionalities, and urea preparation from ammonium isocyanate<1993GEP4127562>, alicyclic <1995BSB411>, N-acyl <1993JGU1675, 1996SC2941> and unsa-turated acyl isocyanates <1994H(38)235>, polyfluorinated <2000BAU1202>, polyunsaturated<1994S56, 2003JOC5512>, azido- and diazine-substituted isocyanates <1993MI655>, glucosyland glucopyranosyl <1994SL919, 1995JCS(P1)377, 2000SL1253, 2001JOC4200, 2002SL1779>,phosphoryl and thiophosphoryl isocyanates <1996JGU349>, radiolabeled <2002MI785>,chlorinated <1992JOU1635, 2001MI351>, chlorosulfonyl <1996JHC943, 1996JMC1243>, aryl-sulfonyl isocyanates <2001WOP23368>, and isocyanato-substituted carboranes <1996POL4355,1997IC4753> has been reported.
Reaction of disubstituted silaazacyclohexanes with isocyanate-terminated polyurethane pre-polymer afforded oligomeric silylureas useful as sealants <1994WOP14820>. The additionof bulky 4-(triphenylmethyl)aniline to linear isocyanates at 40 �C in the presence of a macrocyclichost allowed for the preparation of nonpolymeric rotaxanes with urea-containing axles<1997SL1184>.
454 Functions Containing a Carbonyl Group and Two Heteroatoms
(b) Chemo-, regio-, and stereoselectivity of the addition. The chemoselectivity of the CuCl-catalyzed carbamoylation of ergoline carboxamide 1 (Figure 1), bearing two reactive nitrogenatoms is determined by the nature of the ligand used <1995SL605>. Thus, the best ligandfor carbamoylation of the indole nitrogen was found to be triethyl phosphite, whereas thechemoselectivity was reversed in the presence of 2,20-bipyridyl.
3-Amino-1H-1,2,4-triazole, also having two potential reaction sites, reacts with substitutedbenzylic isocyanates exclusively at the ring nitrogen with the amino substituent remaining intact<2002MI109>. A similar trend was observed on carbamoylation of 2-arylaminothiadiazolidiniumchloride <1993H(35)1237>.
2-Substituted 1-methylperhydropyrimidines 2 (R1=Me, Et, i-Pr, Ph), existing in equilibriumwith minor, but more reactive open-chain tautomers, N-[3-(methylamino)propyl]imines,react with isocyanates R2NCO (R2= t-Bu, Ph, Bn) producing either ureas 3 or 4 (Scheme 1)<1997HCA966>. The chemoselectivity depends mostly on the bulkiness of the R1 substituent withsmaller R1 substituents favoring the cyclic products 3.
The reactions of isocyanates with �,�-unsaturated amines bearing �-hydrogen, such as 2,2-diaminoacrylonitriles <1994JHC329> or N-monosubstituted �-aminovinyl trifluoromethyl ketones 5(Scheme 2) <2000TL10141, 2003T1731>, give either C-addition products e.g., 6, or ureas e.g., 7,with the nature of the predominating product depending both on the reactant substitution andthe reaction conditions. Generally, the increase in the steric hindrance caused by N-substituents orthose in the �-position to the amino group or higher reaction temperatures favor the formation of theC-addition products, whereas the use of more polar solvents and addition of nucleophilic catalysts(pyridine, triethylamine) shifts the equilibrium toward the ureas. The effect of isocyanate componentvariation is less pronounced.
The similar effect of the N-substituents was observed in reactions of acyl or phosphorylisocyanates with 2-amino-1-propenyl phosphonates <1993JGU1675>.
N
N
ON
NMe2
H
H
H
H
1
Figure 1 Ergoline carboxamide: two reactive nitrogen atoms.
N N
R1Me
NHR2
O
N N
R1Me H N
MeNR2HN
O R1
R2NCO R2NCO
23 4
Scheme 1
R2
HN
R1
CF3
O
NHTs
O
R2
HN
R1
CF3
OR2
N
NH
R1
CF3
O
O
Ts
TsNCO TsNCO
56 7R1 = H, Me, Ph;
R2 = H, Me, t-Bu, PhCH2, etc.
Scheme 2
Functions Containing a Carbonyl Group and Two Heteroatoms 455
When optically active amines or isocyanates are used, the reaction proceeds without race-mization affording optically active ureas and their derivatives <1994JOC6487, 2000M463,2001JOC4200>.
(c) Experimental techniques and solid-phase synthesis. A series of 1,3-diaryl ureas was con-veniently prepared in 80–93% yields by addition of anilines to 2-nitrophenyl isocyanate undermicrowave irradiation conditions <2003MI425>. An automated solution-phase parallel synthesisapproach has been successfully implemented for the preparation of numerous urea libraries.To eliminate the major problem of this approach, time-consuming work-up and purification,a series of scavengers, both small-molecule and on a solid support, has been developed. Thus,excess of an isocyanate could be effectively quenched using a fluoro-tagged primary amine<1999JOC2835>, aminomethyl polystyrene <1998JCS(P1)3127> or microgel-supportedtris(2-aminoethyl)amine <2002JCO436> and removed from the reaction medium by simplephase-separation or filtration, respectively. On the other side, the excess of an amine could bereadily removed with fluoroalkyl-substituted isatoic anhydride or isocyanate <2003TL2065>,while the control over the unwanted amine presence could be carried out using ‘‘self-indicating’’resins with pH-dependent color <2003JCO632>.
Lately, solid-phase synthesis has become the major approach to the preparation of urealibraries and several procedures based on either the resin-bound isocyanate <1999TL2749,1999TL4501, 2002MI81> or the resin-bound amine component <2000JCO710, 2001JCO189,2001SL697, 2001TL1973, 2002JCO285, 2002OL597, 2002OL4033, 2003TL811> have been devel-oped. m- and p-Ureido-substituted arylboronic acids were readily synthesized in 65–92% yieldsand with >95% purity via the preliminary deactivation of the acid functionality by condensationof an aminophenylboronic acid with resin-bound diethanolamine followed by treatment of thepolymer-supported boronate thus prepared with an isocyanate and mild acidic cleavage from thesolid support <2002JOC3>.
(ii) Additions of amines to isocyanates with formation of cyclic ureas
(a) Solution-phase reactions. Reactions of isocyanates with amines, bearing a suitably locatedadditional functional group sensitive to nucleophilic attack, are often followed by the intramolecularreactions of the nitrogen atom of the newly formed urea fragment with formation of five- orsix-membered cyclic ureas. These ring closure reactions could be further subdivided into substitutionand addition reactions, the former being more widely exploited. This isocyanate addition/intramole-cular substitution approach generally uses �- or �-amino acids and esters as amine components,and the ring closure step includes intramolecular acylation of the newly formed urea fragment (e.g.,Scheme 3). This procedure is most commonly applied to the preparation of fused polyheterocyclicsystems <1993JHC897, 1993S111, 1994CPB2108, 1994JHC77, 1994JHC1569, 1994JOC1583,1996TL5835, 1997WOP47626, 2002CPB1379, 2002JHC417, 2003JMC113>, but was also usedfor the synthesis of monocyclic substituted tetrahydropyrimidinediones <2000TL4307>, chiralhydantoins <2003OL2555>, and 5-alkoxyhydantoins <1997JOC3230>.
Ethoxycarbonylhydrazones 8 of aromatic aldehydes and ketones react with 2 equiv. ofan isocyanate in triethylamine with formation of intermediates 9, which immediately undergointramolecular N-acylation/ring closure to give imino-substituted triazinetriones 10 (Scheme 4)<1998JHC261>.
HO COOH
NH
NH
R1 R1 ONH
N
HO COOH
NHR2 N
O
O
R2H
NH
N
HO
R1reflux
acetone/DMSO
R1 = H, Me;
R2 = Me, Et, n-Pr, Ph
R2NCO
30–82%
Scheme 3
456 Functions Containing a Carbonyl Group and Two Heteroatoms
On carbamoylation of 2-methylimidazoline, three equivalents of an aryl isocyanate are con-sumed affording hexahydroimidazo[1,2-c]pyrimidine-5,7-diones in good yields <1994BAU1430>.
Intramolecular addition reactions, realized as a second step in one-pot preparation of cyclicureas, include: (a) addition to a carbonyl group <2003JOC754>; (b) addition to a thiocarbonylgroup followed by H2S elimination <2002HAC199>; (c) addition to a carbon�carbon doublebond of enamines <1998S967>; (d) addition to a carbon�nitrogen double bond of imines<1998PHA607, 2001JCS(P1)1241>, isothiocyanates <1993IJC(B)779>, oximes <1999T475>,diazo compounds <2002JMC5448> or methyleneamines, generated in situ by retro-Mannichreaction of hexahydro-1,3,5-triazines <1995JHC995>; (e) addition to a carbon�carbon<1995JHC1141> or carbon�nitrogen <2000PS(160)141, 2001EJO1695> triple bond. The lattercould further be followed by another cyclization reaction <1994AP469> or rearrangement<2001JCS(P1)1241> thus providing access to highly substituted polyheterocyclic systems.
(b) Solid-phase synthesis. There are two major approaches to the solid-phase synthesis ofheterocycles with a urea fragment. The first is based on the direct construction of the desiredheterocyclic ring on the solid support using the isocyanate addition/cyclization procedures,described above for solution-phase synthesis, followed by simple cleavage from the resin. Therepresentative examples of this approach include: preparation of quinazoline-2,4-diones fromresin-bound 2-aminobenzoates <1996TL4439>, 1,3-disubstituted uracils <2000TL1487> and1,3,5-triazine-2,4,6-triones <2002JCO484> from �-amino esters, 1,3,5-triazine-2,4-diones fromresin-bound guanidines <2001JCO278>, and trisubstituted triazinobenzimidazolediones frompolymer-supported 2-iminobenzimidazoles <2002JCO345>.
In the second approach, the acyclic urea fragment is constructed while on a solid support.The subsequent cleavage from the resin releases a reactive functional group (most commonly,carboxylic group), which intramolecularly reacts with the nitrogen atom of the urea unit affordingthe corresponding cyclic ureas. This approach was successfully used for synthesis of functionalizedhydantoins <1996TL5835, 1997TL4603, 1998MI129, 1999TL5841, 2000TL7409, 2001TL1973>,spiro-hydantoins <2001JCO171>, tetrahydrouracils <1998MI139>, and 1,2,4-trisubstitutedurazoles <2002JCO491>.
(iii) Self-condensation and cycloaddition reactions of isocyanates
(a) Dimerization and trimerization reactions. Catalytic cyclodimerization and cyclotrimerizationreactions of isocyanates with formation of symmetrical 1,3-diazetidine-2,4-diones 11 or isocyanu-rates 12, respectively, are well known (Scheme 5). The direction of the cyclocondensation dependspredominantly on the catalyst and the reaction conditions used.
R1
R2
N
HN
O
OEt NN
O
N
EtOR3O
R2R1 O
NHR3 N
OR2
R1
N
N
O
OR3
R3NR3NCO (2 equiv.)
Et3N, rt
8 9 10
R1 = Me, Ph, 4-ClC6H4, 4-MeC6H4;
R2 = H, Me
15–79%
Scheme 4
N N
O
O
R RN
N
N
O O
OR
R
RRNCO
11 12
Scheme 5
Functions Containing a Carbonyl Group and Two Heteroatoms 457
A wide variety of catalysts for high-yielding trimerization of isocyanates includes fluoridesalts <1993JOC1932>, tricyclic proazaphosphatrane and its derivatives <1993AG(E)896,1994JOC4931>, potassium or sodium piperidinedithiocarbamate under conventional or micro-wave heating <2000JCR(S)145>, sodium p-toluenesulfinate <2002BCJ851>, trialkyl amines<1994NKK146>, tetrasulfido tin complexes <1999OM4700>, and transition metal complexese.g., CpCo(PPh3)Me2, in supercritical carbon dioxide <2001JOM(626)227>. Even minor changesin the catalyst composition can affect the product distribution: thus, self-condensation of PhNCOin the presence of the oxoniobocene complex [Cp*2Nb(O)OMe] resulted in exclusive formationof triphenyl isocyanurate, whereas the [Cp*2Nb(O)H]-catalyzed reaction gave a mixture ofdimerization and trimerization products with the former predominating <2001JOM(634)47>.
The exclusive or predominant formation of 1,3-diazetidine-2,4-diones 11 occurs either onheating without a catalyst <2001JOU1747> or under catalysis with pyridine or 2- or 4-picolinesunder high pressure <1994NKK146>. In the latter case, the selectivity of the dimerizationincreases with the increase in pressure or in amount of the pyridine catalyst, whereas polarsolvents, such as acetonitrile, favor the trimeric product. The predominant dimerization of phenylisocyanate was also observed when 1,5-diazabicyclo[5.4.0]undec-5-ene (DBU) was used as acatalyst <1994JOC4931>.
The reaction of tungsten hexachloride with excess of ethyl isocyanate in dichloroethane led toinsertion of three isocyanate molecules into one of the tungsten�chlorine bonds furnishing thetungsten complex WCl4[(EtNCO)3Cl], which on hydrolysis gave isocyanurate 12 (R=Et)<2002MI673>.
Self-condensation of isocyanates under aqueous (aq.) basic conditions affords acyclic symme-trical ureas. Thus, heating 3-alkoxyphenyl isocyanates in aq. NaOH gave the correspondingN,N0-bis(3-alkoxyphenyl)ureas in 72–83% yields <1994CCC495>. Aromatic isocyanates werereadily converted into symmetrical 1,3-diaryl ureas in 85–95% yields in aq. pyridine at 20 �C<1999S1907>.
(b) Other cycloaddition reactions of isocyanates. SbCl5-Catalyzed 1,3-dipolar cycloaddition ofisocyanates with �-chloro-substituted azo compound 13 afforded the corresponding triazoloniumhexachloroantimonates 14 in moderate yields (Equation (2)) (where TMSNCO indicatestrimethylsilyl isocyanate) <1993T9973>, whereas 1,3-dipolar cycloaddition of isoquinoliniumarylimides, generated in situ from N-(arylamino)isoquinolinium halides, gave the correspondingtriazoloisoquinolones in 87–99% yields <1998EJO379>.
Cl NN
Ar
MeMe
NN N
O
R Ar
Me Me+
SbCl6
i. SbCl5, CH2Cl2,
–60 °C
ii. RNCO
–
13 14
R = H (from TMSNCO), t-Bu, Ph
42–68%
Ar = 2,4,6-Cl3C6H2
ð2Þ
Heating phenyl isocyanate with nonsymmetrical azines 15 in xylene triggered two consecutive1,3-dipolar cycloaddition reactions yielding heterocycles 16 with three fused five-memberedrings (Equation (3)) <2002TL6431>. 1,3-Dipolar cycloaddition of phenyl isocyanate to �-iminothioamides occurs with sulfur elimination affording 4-amino-1,3-dihydroimidazol-2-ones<1997BSF623>.
H2CC
R
NN
Me Me
OMe
N N
NO
MeMe
Ph
OMe
R
PhNCO
15 16
R = Me (64%), Et (68%)
Xylene
Reflux
ð3Þ
The in situ 1,3-dipole generation via thermal or palladium-catalyzed ring opening of three-membered heterocycles, such as functionalized aziridines <1995JA4700, 2000JOC5887>, bicyclicaziridines <2000SL1779>, or oxaziridines <2001TL9131>, in the presence of isocyanates
458 Functions Containing a Carbonyl Group and Two Heteroatoms
presented a convenient method for regioselective preparation of substituted imidazolin-2-ones,pyrazolo[1,2-a][1,2,4]triazolones and 1,2,4-oxadiazolidin-3-ones, respectively. A similar azetidinering opening/isocyanate cycloaddition of 2-vinyl azetidines under palladium catalysis<2001SL914> or of 2-azabicyclo[2.2.0]hex-5-enes <2003JOC1626> afforded the correspondingvinylic or azetidine-fused tetrahydropyrimidin-2-ones in moderate to excellent yields.
Chiral 2-alkenyl dihydrooxazoles 17 (X=O) react with 2 equiv. of aryl and arylsulfonyl isocyanatesto give nonracemic dihydropyrimidone derivatives 18 (Scheme 6) via asymmetric hetero-Diels–Alderreaction followed by the addition of a second molecule of the isocyanate to the cycloadduct<1997CC2311>. The thia analogs 18 (X=S) were obtained in the similar reactions of 17 (X=S)with tosyl isocyanate; however, cycloaddition with less reactive phenyl isocyanate afforded 1:1 adduct19 as the sole product <1999SL1379>.
Other examples of hetero-Diels–Alder cycloaddition reactions with isocyanates include thepreparation of benzimidazolotriazinones and benzothiazolotriazinones from the correspondingN-(2-heteroaryl) arylimines <1993SC1427> and of imidazo[5,1-d]-1,2,3,5-tetrazin-4-one(temozolomide) and analogs from 5-diazoimidazole-4-carboxamide <1995JCS(P1)2783,2002JMC5448>.
[2+2+2]-Cycloadditions of N-trimethylsilyl imine 20 with various isocyanates affordedunsymmetrical 1,3,5-triazine-2,4-diones 21 (Scheme 7) in 75–96% yields <1995S1529>. Impor-tantly, two different isocyanates could be added stepwise allowing for introduction of differentsubstituents on N-1 and N-3 atoms of the cycloadducts. Analogous [2+2+2]-cycloadditionof 3-aryl-3,4-dihydroquinazolines with 2 equiv. of phenyl isocyanate gave the correspondingquinazolinotriazinediones <2000EJO2105>.
Benzotriazolyl-substituted iminium chloride undergoes [1+2+2]-cycloaddition with 2 equiv. ofphenyl isocyanate to give, after quenching with an appropriate nucleophile, functionalizedhydantoins in moderate yields <1996JHC1935>.
Conjugated heteroarylvinyl iminophosphoranes react with alkyl or phenyl isocyanates via the aza-Wittig-type reaction and formation of carbodiimide intermediates to afford heteroarylmethylidene-substituted imidazoline-2,4-diones in moderate yields<1994JOC6413>. A similar approach was usedfor the solid-phase synthesis of 2-imino-4-oxo-1,3,5-triazino[1,2-a]benzimidazoles from resin-bound2-benzimidazolyl iminophosphoranes <2003JCO155>.
NX
R1
R2
N
N
X O
R3R1
R3HN
O
R2
N
N
S O
PhPh
PhNCO
171819
(X = S, R1 = Ph,
R2 = H)
55%
25–94%
2 R3NCO
X = O; R1 = Me, Et, Ph; R2 = Et;
X = S; R1 = Ph; R2 = H, (i-Pr)3SiOCH2
R3 = Ph, 4-BrC6H4, Ts, etc.
Scheme 6
N
N OTMS
R1
CH2OTBDMS CH2OTBDMS
N
O NTMS
R1
HN
N
NR2
R1O O
CH2OTBDMS
NTMS
CH2OTBDMS
R1NCOR2NCO
75–96%
20 21
Scheme 7
Functions Containing a Carbonyl Group and Two Heteroatoms 459
6.16.1.1.2 Reactions with metal cyanates
Reactions of primary amines with sodium or potassium cyanates (Equation (4)) represent the mostcommonmethod for thepreparationofmonosubstitutedureas.As anamine component, benzylic amines<2002JOC8827>, anilines <2000EJM879>, sterically constrained primary amines <1994TL8891>,�-amino acids <2001JCS(P2)1247, 2001MC32, 2002JOC8827>, �-amino acids <2001MC32>, andamino sugars <2002JCS(P1)1982> were successfully used. The kinetics of N-carbamoylation of�-amino acids with potassium cyanate were studied in detail <2001JCS(P2)1247>.
RNH2 MOCN N NH2
OR
H(M = K, Na)
+ ð4Þ
Secondary aromatic amines <2003JOC754>, hydroxylamines <1994TL6017>, and even aza-heterocycles, such as 4,5-disubstituted 2,4-dihydro-1,2,4-triazol-3-ones <1995GEP4343595>, werealso reacted with potassium cyanate to afford the corresponding urea derivatives. When theamine component has a suitably located carbonyl group, the latter undergoes intramolecularcondensation with the newly formed urea fragment <2002JOC5527, 2003JOC754>.
The reaction of KOCN with haloalkyl acrylates and methacrylates 22 gave the correspondingsymmetrical ureas 23 (Equation (5)) <1993TL3857>. The presence of water is required tosuppress the trimerization of the intermediate isocyanates.
H2C
RO(CH2)nNH
O
CO
2
H2C
RO(CH2)nX
O
KOCN
aq. MeCN
22 23
R = H, Me; n = 6, 8; X = Cl, Br
69–85%
Bu4NBrð5Þ
Treatment of acyl or sulfenyl chlorides with silver cyanate in ether or aromatic solvents isa convenient approach to in situ generation of isocyanates which are unstable and/or notreadily available. The subsequent addition of amines <1995TL6257>, N-alkoxyamines<1995JHC1625>, or hydrazines <1995PHA379> allows for the preparation of the correspondingfunctionalized ureas and sulfenyl carbazides.
6.16.1.1.3 Carbonylation of amines
A convenient approach to the conversion of primary and secondary amines into symmetricalureas is the catalytic oxidative carbonylation of the amines with CO/O2 (Equation (6)). A widevariety of catalysts has been found effective for this reaction, including selenium compounds<2000MI355, 2000USP6127575>, manganese-based catalysts <1993JCA631>, resin-immobilizedgold <2002JCA548>, Pd/H2SO4-modified ZrO2 <2001TL2161>, sulfur <1993HAC455>, polymer-supported palladium�copper catalyst <2000MI55>, PdI2/KI catalytic system <2003CC486>,and palladium methoxycarbonyl complexes in the presence of CuCl2 <1994JOM(470)249>.Electrocatalysis has also been applied <2001MI799>. Primary aromatic amines and secondaryaliphatic amines are generally less reactive than primary alkylamines, allowing for the prepara-tion of unsymmetrical ureas by oxidative carbonylation of primary alkylamines in the presenceof excess of a less reactive amine <2001TL2161, 2003CC486>.
N N
OR1
R2
R3
R4
R1R2NH +CO
Catalystor ∆
R3R4NH ð6Þ
High-pressure Se-catalyzed carbonylation of amines and diamines with [11C] carbon monoxideprovided access to 11C-labeled cyclic and symmetrical acyclic ureas <2002JOC3687>. Treatmentof N,N0-di(t-butyl)diaziridinone with Ni(CO)4 under CO atmosphere resulted in CO insertion intothe N�N bond giving the ring expansion product, symmetrical N,N0-di(t-butyl)diazetidinedione,in 75% yield <1999H(50)67>.
460 Functions Containing a Carbonyl Group and Two Heteroatoms
Instead of oxygen, iodine could be used as an oxidant. Thus, tungsten-catalyzed carbonylationof aliphatic primary and secondary amines and diamines in the presence of iodine furnisheda series of acyclic <2000JMOC(A)11, 2000JOC5216> and cyclic ureas <1999OL961,2002JOC4086, 2003JOC1615>. This reaction is compatible with acid-sensitive and fluoride-sensi-tive functional groups. A nitroarene, such as 3-(trifluoromethyl)nitrobenzene, was also used as anoxidant for Se-mediated conversion of primary alkylamines into symmetrical 1,3-dialkyl ureas<1995JGU88>.
The ability of carbon monoxide to reduce nitroarenes to the corresponding anilines has beenexploited in the preparation of 1,3-diaryl- <1993USP5198582, 2002JCA255, 2003JMOC(A)135>and 1-aryl-3-cycloalkyl ureas <2003JMOC(A)135>. Selenium is the most common catalyst forthis process, although a polymer-supported rhodium catalyst has also been applied<2002JCA255>. In these reactions the nitro compound acts as both the reagent and an oxidant.
The use of toxic carbon monoxide could be avoided by replacing it with CO2. Thus, 1,3-dialkylureas and 2-imidazolinones were successfully prepared from the corresponding amines ordiamines and CO2 at 80 �C using the Ph3SbO/P4S10 catalytic system <1992JOC7339>. Trisub-stituted ureas were also synthesized under these conditions in moderate yields, but the attemptsto prepare a tetrasubstituted urea, other than tetramethylurea, failed. This shortcoming waslater overcome by carrying out the reaction in the presence of carbon tetrachloride and1,8-bis(dimethylamino)naphthalene <2002JOC9070>.
Purging CO2 into a mixture of a primary aromatic amine and DBU in pyridine ortetrahydrofuran (THF) followed by addition of the trimethylamine–sulfur trioxide complex as adehydrating agent gave the corresponding 1,3-diaryl ureas in 23–87% yields <1995SC2467>.The analogous reaction of ammonia with carbon dioxide with removal of water usingwater-selective membranes allowed for the large-scale preparation of unsubstituted urea<2001WOP04085>.
Heating primary aromatic or aliphatic amines with ethyl acetoacetate at 180 �C in thepresence of the commercially available zeolite, HSZ-360, led to carbonylative dimerization ofthe amines affording symmetrical 1,3-diaryl or 1,3-dialkyl ureas as the sole reaction products<1998CC513, 1999JOC1004>. The reaction presumably occurs via the intermediate formationof the corresponding acetoacetamide, which undergoes C�C bond cleavage on further reactionwith an amine.
6.16.1.1.4 Substitution reactions of amines with phosgene and its equivalents
(i) Reactions of amines with phosgene
Despite its toxicity, phosgene is still utilized, although to a lesser degree than other carbonic acidderivatives, for the conversion of amines into ureas (Equation (7)). The reaction generally takesplace in inert solvents (toluene, dichloromethane, THF) at 0–5 �C in the presence of a base(aq. NaHCO3, aq. NaOH, triethylamine, etc.).
N N
O
R1
R2
R3
R4
COCl2+R1R2NH + R3R4NH ð7Þ
The reactions of phosgene with 2 equiv. of an amine were used for the synthesis of a varietyof symmetrical ureas, including N,N0-carbonylbis(azoles) <1996EUP692476, 1997JOC4155,2000GEP19830556, 2002GEP10035011> and cyclic ureas, such as 4,5-diaminoimidazol-2-ones<1998EJO183>, imidazolidin-2-ones and their fused analogs <1993T4419>, tetrahydropyrimidin-2-ones <2002HCA1999>, and hexahydroazepin-2-ones <1997JOC5380, 1998JOC9252>.
More useful, however, is the synthesis of unsymmetrical ureas by consecutive treatment ofphosgene with two different amines with in situ formation of an isocyanate intermediate.A combination of two aromatic amines <2002WOP83642>, two amino acids <2001OL2313>,or an aromatic or heterocyclic amine and O-alkyl hydroxylamine <1996TL2361, 2000CCA569>were all successfully used. 14C-Labeled phenylureas bearing photoactive azido and diazine groupswere also prepared by this procedure <1993MI655>.
The reaction with phosgene was also employed in the solid-phase synthesis of functionalizedN-carbamoyl indolines <2000JA2966>.
Functions Containing a Carbonyl Group and Two Heteroatoms 461
(ii) Reactions of amines with carbamoyl chlorides
Reactions of carbamoyl chlorides with amines (Equation (8)) are comparatively seldom used forthe urea synthesis, probably due to a limited range of available carbamoyl chlorides.
N N
OR1
R2
R3
R4
R1R2NH + R3R4NCOCl ð8Þ
Dialkyl and alkyl aryl carbamoyl chlorides were successfully used for carbamoylationof azaheterocycles, such as triazoles <2002BCJ567>, oxazolidinones <2002JA9060> andtetrazolinones <1995EUP646577>, arylhydrazines <1994S782>, and O,O0-polyoxyethylenebis(hydroxylamine)s <1993JOU1464>, the latter being dicarbamoylated. In contrast, treatmentof O,O0-polyoxyethylene bis(hydroxylamine) with N-carbazolylcarbonyl chloride gave exclusivelythe monocarbamoylation product, albeit in a moderate yield <2001SL682>.
Carbamoylation of pyridines affords the corresponding N-carbamoylpyridinium halides<1996EUP692473>; however, when �-chloroformyl arylhydrazines 24 are used as the reac-tants, further attack of the free amino group at the 2-position of the pyridine ring occurs toafford [1,2,4]triazolo[4,3-a]pyridine-3-ones 25 (Equation (9)) <2001MI1135>. The analogouscyclization reaction was observed with isoquinoline and pyridazine <2002MI239>. Pyrimidine,however, was unreactive under the reaction conditions, whereas 1,3,5-triazine, thiazole, and1,4,5,6-tetrahydropyrimidine underwent ring opening of the original heterocycle to affordfunctionalized 2,4-dihydro-1,2,4-triazol-3-ones in good yields.
NAr
NH2
Cl
O
NN
NN
O
Ar
24 25
Ar = Ph, 4-ClC6H4, 4-MeC6H4
+
excess
12 h
75–84%
100 °C
ð9Þ
Carbamoylation of N-alkyl hydroxylamines with N-cyano-N-arylcarbamoyl chlorides fol-lowed by intramolecular addition of the N-hydroxy group to the nitrile furnished the corre-sponding 1,2,4-oxadiazol-3-ones in 93–98% yields <2002SC803>. Analogous tandemcarbamoylation/intramolecular cyclization procedure was used for preparation of thiatetraazain-denones and -fluorenones from mercapto-substituted triazoles and benzimidazoles, respectively<2000M953>.
(iii) Reactions of amines with chloroformates
Chloroformates, bearing two good leaving groups of different nucleofugicity, represent conveni-ent reagents for step-by-step CO-linking of different amines (Scheme 8) and preparation ofunsymmetrical ureas without isolation of the intermediate carbamates.
The most widely used are phenyl and 4-nitrophenyl chloroformates, although some alkyland chloroalkyl chloroformates are also applied. This approach was successfully used for thepreparation of di- and trisubstituted ureas <1996SC4253, 2002JAP(K)212160>, N-carbamoylamino esters <1996OPP173, 1997TL5335>, and N-arylcarbamoyl aminopyrazoles<2002WOP66442> and indolines <2000SC1937>. The procedure was also applied to solid-phase synthesis of functionalized ureas <1994TL4055, 1996TL4439>.
NR1
R2OR3
O
NR1
R2N
OR4
R5Cl OR3
OR1R2NH +
R4R5NH
Scheme 8
462 Functions Containing a Carbonyl Group and Two Heteroatoms
When a substrate molecule has two amino groups of different reactivity, intramolecularcyclization can occur. Thus, heating pyrazolyl hydrazides 26 with trichloromethyl chloroformategave pyrazolotriazinediones 27 (Equation (10)) <1999S453>, whereas condensation of�-hydrazono selenamide with methyl chloroformate afforded selenated 1,2,4-triazine-3-one in49% yield <2000PS(164)161>.
HN
NH
ArNNH
R
O
Cl
O
OCCl3 N
NNH
N
O
O
R
Ar
+Toluene
Reflux, 1 h
53–68%
26 27
R = H, Cl, Br, NO2
Ar = Ph, 2-MeC6H4, 3-ClC6H4
ð10Þ
(iv) Reactions of amines with carbamates and thiocarbamates
Carbamates represent the carbonic acid derivatives most widely used in the urea synthesis andare generally prepared by partial aminolysis of chloroformates (see Scheme 8). O-Phenyl and O-t-butyl carbamates are the most popular, the latter being readily available from aminesand (BOC)2O. Aminolysis of carbamates (Equation (11)) usually requires the presence of a base(triethylamine, DBU, NaHCO3, etc.) and, when necessary, can be promoted by addition ofchlorosilanes <1998JOC8515, 2000JOC3239> or by heating over �-Al2O3 <2000TL6347>.
N N
OR1
R2
R3
R4
R1R2NH + NR3
R4X
R5O
X = O, S
ð11Þ
The reaction is tolerant to a wide variety of the functional groups on both the carbamate andthe amine reactants allowing for the preparation of multiply functionalized ureas, including:acryloyl ureas <1993EUP556841>, hydroxy-substituted ureas <1997S1189, 2001TL1445>,polyfluorinated ureas <2000JOC1549>, arylsulfonyl <2001WOP05354> and heteroarylsulfonylureas <1995WOP00509, 2001MI404>, carbamoyl diamino acids <1994EUP629612>,N-carbamoyl nucleosides <1994HCA1267>, carbamoylamino glycosides <2000OL2113,2001TL1445> and N-carbamoyl piperidines <1997S1189, 2000JOC1549>, piperazines<1996SL507>, indolines <2001JHC451, 2002TL6649>, dihydroquinolines <2000TL6387>, anddihydrophthalazines <2002JHC989>. The groups sensitive to the transformation include someamino protecting groups, such as N-benzoate <2000MI405> and N-phenoxycarboxylate<1992JOC5020>.
The carbamate aminolysis has also been applied to the solid-phase preparation of N-carbamoyldihydroquinolinones <2000SL45>, N-carbamoyl guanidines <1999JCO361>, oligoureas<2000TL1553>, and libraries of di- and trisubstituted ureas <1998JOC4802, 2002MI81>.
On treatment with amines, cyclic carbamates, such as 2-oxazolidinones <1996TL1217> or1H-thieno[2,3-d][1,3]oxazine-2,4-diones <1998T10789>, undergo aminative ring opening toafford hydroxy- or carboxy-functionalized ureas, respectively.
When a reactive amino or imino function is already present in the carbamate or activated in situ bydeprotection, the intramolecular carbamoylation can occur allowing for access to variously substi-tuted hydantoins <1997TL2065, 1998CC2703, 2000T3697>, optically active polycyclic ureas<1996T8581>, triazinediones <2002HCO123>, and fused tetrazinones <2002JCS(P1)1877>.
Cyclic ureas could also be prepared by intermolecular carbamoylation if the carbamate and/or amine component have additional reactive functional groups. Thus, hydantoins 29 (Equation (12))and their dehydro derivatives were prepared by condensation of N-BOC amines 28 having the
Functions Containing a Carbonyl Group and Two Heteroatoms 463
activated �-position with imines <1996JOC428, 2001JOC2858, 2002EJO301> and nitriles<1994JHC1689>, respectively. Cyclocondensation of �,�-unsaturated �-amino acids or their esterswith carbamates afforded uracil derivatives <1995JAP(K)0761975, 1998USP5817814>, whereas thereaction of dihydrobenzodiazepinethione with ethyl carbazate gave fused triazolobenzodiazepinonesin moderate yields <2003JMC3758>. Pyrazolo[1,5-d][1,2,4]triazinones were prepared via the analo-gous cyclocondensation of 5-acylpyrazolyl-1-carboxylates with phenylhydrazine <2002JOU602>.
R2N
BOC
R1
R3 N
OMes-BuLi
N NR2
R1 R3
O OMe
+THF or Et2O
–78 °C 28 29
R1 = Ph, R2 = 4-MeOC6H4
R1 = benzotriazol-1-yl, R2 = PhCH2
R3 = Ph, 4-MeOC6H4, 2-furyl, etc.
22–92%ð12Þ
Aminolysis of S-methyl alkylthiocarbamates with primary or secondary alkyl and cycloalkylamines in acetonitrile <1998TL3609>, or with primary sulfonamides in toluene in the presence ofDBU <2000SC3081>, gave the corresponding ureas and sulfonylureas in 60–89% yields withoutracemization. Although benzamide and thiobenzamide were unreactive under these conditions,aryl-substituted ureas were prepared in 81–100% yields by treatment of thiocarbamates withgenerated in situ aniline carbanions <2000SC1675>.
Aminolysis of S-allyl N-acylthiocarbamates with a variety of amines in benzene-water two-phase system <1993CCC575> or with phenylhydrazine in benzene <1993MI64> afforded thecorresponding acyl ureas and acyl semicarbazides, respectively.
Thermolysis of N-aryl carbamates at 230–240 �C produces the corresponding symmetrical1,3-diarylureas in 42–97% yields <1994RRC397>.
(v) Reactions of amines with ureas
(a) Preparation of acyclic ureas via disubstitution of symmetric ureas with amines. Microwaveirradiation of a mixture of an aromatic amine or phenylhydrazine with unsubstituted ureaafforded the corresponding symmetrical ureas in moderate-to-good yields (Equation (13))<1999JCR(S)710>. The addition of a suitable energy-transfer solvent, such as N,N-dimethylacetamide, to the reaction mixture resulted in significant improvement in the product yields<2000MI24>. Primary aliphatic amines <2000MI24> and 2-aminopyridines <2001HCO233>reacted in a similar manner.
H2N NH2
O
RHN NHR
ORNH2 +
R = alkyl, aryl, 2-pyridyl, PhNH
40–90%
Microwave
ð13Þ
However, of all the symmetrical ureas, commercially available, easily handled, crystallineN,N0-carbonyldiimidazole (CDI) is the most widely used as a phosgene equivalent. Significantlylower reactivity of an N-carbamoylimidazole, formed after substitution of one imidazolylgroup with an amine, compared to CDI itself allows one to carry out the disubstitutionconsecutively using two different amines or their analogs. This approach was appliedin the solution-phase synthesis of optically active dipeptides <1997TL5335, 2002JA9356>,N-carbamoyltetrahydropapaverines <2002CPB1223> and 4-hydroxysemicarbazides<2000HCO55, 2002HCO321>, and in the solid-phase synthesis of unsymmetrical polyfunctional1,3-diaryl ureas <1997BOC277>.
Although N-carbamoyl imidazoles, formed from secondary amines and CDI, were found to beunreactive toward coupling with secondary amines, these intermediates could be activated by theirconversion into the corresponding imidazolium salts <1998TL6267>, thus making this approachsuitable for the preparation of tetrasubstituted ureas.
464 Functions Containing a Carbonyl Group and Two Heteroatoms
Instead of CDI, 1,10-carbonylbis(benzotriazole) was used for preparation of tetrasubstitutedureas (no activation is required in this case) <1997JOC4155> and for solution- and solid-phasesynthesis of dipeptides <1998TL7811>.
(b) Preparation of acyclic ureas via monosubstitution of ureas with amines. Condensation ofunsubstituted urea with a sterically hindered secondary amine in a strongly acidic medium<2000CHE837> or with a heteroaromatic amine, such as pyrazole, under thermal conditions<1992EUP508191> results in substitution of only one of the urea amino groups providingproducts of the general formula R1R2NCONH2. On treatment of N-phenylurea with a varietyof amines, the unsubstituted amino group of the urea is cleaved, thus allowing access to a series of1,3-di- and trisubstituted ureas <1992M607, 1995GEP4405056>. The same products could beprepared by reaction of 1,3-diphenylurea with amines <1993OPP600>.
Analogously to the second step of the CDI aminolysis, reaction of independently preparedN-carbamoyl imidazoles with amines leads to the substitution of the imidazolyl moiety withthe amino group <1994WOP06825>. Similarly, heating resin-bound 1-carbamoyl-1,2,3-benzotriazolewith primary or secondary amines results in the nucleophilic displacement of the benzotriazolemoiety releasing the newly formed unsymmetrical urea in the solution <2001JCO354>.
(c) Preparation of cyclic ureas. The most widely used procedure for the preparation ofcyclic ureas via the substitution pathway is the condensation of urea or its derivatives withdiamines. Unsubstituted urea or CDI are generally used as phosgene equivalents. This approachwas applied to the preparation of 2-imidazolidinones <1993T4419>, 2-benzimidazolones<2002JCO320>, tetrahydropyrimidin-2-ones <2002HCA1999>, hexahydroazepin-2-ones<1996USP5508400, 2002OL4673>, hexahydro-1,3,6-triazocin-2-one <1995EUP670316>, andmacrocyclic ureas <1993USP5206362>. A series of functionalized hydantoins were synthesizedfrom the corresponding resin-bound 1,2-diamines <1997TL931, 2001JCO68, 2002JCO175>.Instead of two amino groups, their analogs, such as amide <1993TL7953>, hydrazine<1999HCO473, 2001JHC1097>, or amidrazone <2002JMC2942> moieties, can participate inthe reaction.
If a second amine, used for the double aminolysis of CDI, features a suitably located carboxylicgroup, the in situ intramolecular cyclization of the newly formed urea can occur giving, forexample, fused imidazolidinediones <1994JHC1235, 2002JHC417>. The similar intramolecularcyclization after formation of the urea fragment was used for solution-phase <2000TL1159> andsolid-phase <2000TL1165> synthesis of 3-aminohydantoins and 3-aminodihydrouracils.
(vi) Reactions of amines with carbonates and thiocarbonates
(a) Preparation of acyclic ureas. Similarly to reactions of ureas with amines, aminolysis ofcarbonates (Scheme 9) could be carried out by consecutive introduction of two different amines ortheir analogs allowing for access to unsymmetrical ureas and their derivatives.
Bis(trichloromethyl) carbonate, or triphosgene, is the most widely exploited. Using the couplingreaction with triphosgene, ureas derived from two different amino acids <1994JOC1937,1999TL2895>, as well as 1-aryl-3,3-dialkyl ureas <1998JCR(S)442>, glucopyranosylureas<2001JOC4200>, �-ureido alkylphosphonates <2000PS(160)51, 2001JCR(S)470, 2001HAC68>,carborane-substituted ureas <2000TL7065, 2001TL5913, 2002JOM(657)48>, ureapeptoid peptido-mimetics <1997TL5335>, and urea-functionalized porphyrins <1998JOC2424> were allsuccessfully prepared. This approach has also been applied to the solution-phase synthesis oftri- and tetrasubstituted ureas from polyethylene glycol-bound amines <2001BMCL271> and tosolid-phase synthesis of peptide C-terminal semicarbazones <1999TL6121>.
NR1
R2XR3
O
NR1
R2N
OR4
R5R3X XR3
O+R1R2NH
R4R5NH
X = O, S
Scheme 9
Functions Containing a Carbonyl Group and Two Heteroatoms 465
Other symmetrical carbonates, such as dimethyl carbonate <2002GC269>, diphenyl carbonate<2001JAP(K)302640>, cyclic ethylene carbonate <1998EUP846679> and bis(1-cyclohexenyl)carbonate <1995JAP(K)06239805>, as well as unsymmetrical diaryl carbonates <1996SC331>were also used. Nitrophenyl carbonates were applied in the solid-phase synthesis of various ureas<1998TL3631> and azapeptides <2000TL3983>.
Although di(t-butyl) carbonate is known to react with amines directly to give N-BOC-protectedderivatives, under catalysis with 4-(dimethylamino)pyridine (DMAP) it reacts with a second equivalentof an amine to give the correspondingureas. This procedurewas successfully applied to primary aromatic<1996SL502, 2000JOC6368>, primary aliphatic amines and resin-bound anilines <1999TL8563>;however, with secondary amines only N-BOC protection was observed <2000JOC6368>.
The condensation of primary alkylamines with S,S-dimethyl dithiocarbonate in methanol or withoutsolvent at 60 �C gave 1,3-dialkyl ureas<1996JOC4175>. Aromatic and sterically hindered alkylaminesare unreactive, whereas dialkylamines give only monosubstituted products i.e., thiocarbamates.
(b) Preparation of cyclic ureas. Condensation of carbonates with diamines leads to theformation of cyclic ureas if the diamine structure allows for nonconstrained ring closure. Thisprocedure has been used for the preparation of benzimidazolones in solution <2001JCA91> andon the solid support <1998TL179>, quinazoline-2,4-diones <2002M1067>, and macrocycliccarborane-substituted ureas <2001TL5913>.
Low-valent titanium-induced carbonylative dimerization of aryl imines in the presence oftriphosgene gave substituted imidazolin-2-ones <2002SC2613>, which were also prepared viaDMAP-catalyzed carbonylative cyclization of 1,2-diamines with BOC2O <2000JOC6368>. Con-densation of S,S-dimethyl dithiocarbonate with appropriate diamines afforded a series of imida-zolin-2-ones, tetrahydropyrimidin-2-ones, and 2-quinazolinone in moderate to good yields<1996JOC4175>.
6.16.1.1.5 Oxidation of thioureas and related compounds
Both acyclic and cyclic thioureas were readily converted into the corresponding ureas (Equation (14))on treatment with bismuth nitrate pentahydrate in acetonitrile at reflux <2003TL591> or inphosphate buffer at 20 �C <2000MI285>. The reaction is chemoselective: although thioamidesare also oxidized, thiono esters and thioketones are essentially unreactive. Inexpensive, stable, andcommercially available Oxone could also be used as an oxidant <2003PS(178)61>; however, inthis case the excess of the reagent is required and a poorer chemoselectivity is observed.
N N
SR1
R2
R3
R4N N
OR1
R2
R3
R4
Oxidantð14Þ
Oxidation of 1,3-di- and trisubstituted thioureas was also carried out using sodium metaper-iodate, sodium chlorite, and ammonium persulfate in water <1997SC2357>, whereas N-aroylureas were prepared via the oxidation of thioureas with bromine in chloroform (Hugershoffreaction) <1994CCC2663>. Potassium iodate (KIO3) was found to be a convenient reagent forthe preparation of N-aroyl ureas <2000SC2635>, N-acylated bis(urea)s <2002SC3373>, andN,N0-diacyl semicarbazides <2000SC3405, 2000SC4543, 2001SC1433> from the correspondingthiocarbonyl analogs. Trisubstituted glucopyranosyl thioureas were readily oxidized with excess ofyellow HgO <2002TL4313>; the disubstituted analogs, however, gave exclusively bicyclic isoureas.
There are few procedures specific for oxidation of cyclic thioureas. These include oxidationwith mercury(II) acetate, used for the preparation of 1,3-diacylimidazolidin-2-ones<1993T4419>, and oxidation with 30% hydrogen peroxide in aq. NaOH, used in synthesisof six-membered cyclic ureas <1994JHC1569, 1999JHC1327>. Tetrazolinethiones were oxidizedto tetrazolinones using unsubstituted oxirane or 2-alkyl epoxides as oxidants <1995EUP643049>.
6.16.1.1.6 Reactions of amines with amides and other carboxylic acid derivatives
Ruthenium-catalyzed carbamoylation of dialkylamines <1992USP5155267> or primary aromaticamines <1997OM2562> with formanilides at 165 �C give the corresponding unsymmetrical di-and trisubstituted ureas in high yields. For reaction with anilines, unsubstituted formamide could
466 Functions Containing a Carbonyl Group and Two Heteroatoms
also be used. Although simple alkyl and cycloalkyl amides are unreactive, �-polychloro- or�-polynitro-substituted aliphatic amides readily undergo �-elimination to give intermediate isocya-nates, which on trapping with ammonia or primary amines afford mono- and disubstituted ureas,respectively (Scheme 10) <1992BAU891, 1994BAU821, 1994CL2299, 1994OPP357, 1999TL3235>.
Curtius rearrangement of acyl azides also produces the intermediate isocyanates as ureaprecursors. The starting acyl azides are usually generated in situ by one of the following methods:(i) reaction of a carboxylic acid with diphenylphosphoryl azide in the presence of a base<2001MI133, 2002MI109, 2002T4225>; (ii) from acyl chlorides and sodium azide <1999S943,2000JHC1247>; or (iii) oxidation of acyl hydrazides with HNO2 <1998JCS(P1)2377>. Thisapproach has also been applied to the synthesis of N,N0-disubstituted ureas from heterocyclicand aliphatic carboxylic acids and resin-bound amines <2000OL3309>.
6.16.1.1.7 Miscellaneous reactions
(i) From carbodiimides
Hydrolysis of carbodiimides produces the corresponding ureas <2000CAR161>, whereas their hetero-cyclizationwith diaryl nitrones<1998SC3665> or 2-(bromomethyl)acrylic acid<1996JHC1259> yieldspolysubstituted 1,2,4-triazolin-3-ones and 5-methylidenetetrahydropyrimidine-2,4-diones, respectively.
(ii) Heterocycle ring–ring interconversions
Variously substituted 1,2,4-triazol-3-ones were prepared by ring opening/recyclization of2-amino-1,3,4-oxadiazoles <2002JCR(S)213> or 5-amino-1,2,4-oxadiazoles (Equation (15))<1996JOC8397> in the presence of a primary amine. The rearrangement of arylhydrazonesof 3-benzoyl-5-amino-1,2,4-oxadiazoles, however, occurs differently with formation of ureido-substituted 1,2,3-triazoles <2002JOC8010>.
N
ONR1
PhN
NNO
R2
PhH
MeOHR2NH2
hν
R1 = NH2, NHMe, NMe2
R2 = H, Me, n-Pr, n-Bu, NH2
57–60%
+
ð15Þ
Heating 3-(2-oxopropyl)benzothiazol-2-ones with excess of a primary amine in HClO4 affords1-(2-mercaptoaryl)imidazolin-2-ones, readily oxidizable in air to the corresponding disulfides<2000PS(158)67>. Oxidative rearrangement of 3-arylimino-2-indolinones occurs with the ringexpansion to give quinazoline-2,4-diones <2000TL5265>.
(iii) Oxidation
Purines and xanthines are readily oxidized to the corresponding 8-oxo derivatives with dimethyl-dioxirane <1995TL2665> or bacteria <1999JCS(P1)677>, whereas oxidation of benzimidazoliumsalts and their N,N0-polymethylene-bridged analogs in air affords the relevant benzimidazolones
R1 NR2
H
O∆ N N
R2
H
R3
R4
OR3R4NH
R2NCO
R1 = CCl3, O2NCCl2, MeC(NO2)2
–R1H
Scheme 10
Functions Containing a Carbonyl Group and Two Heteroatoms 467
in high yields <1994TL33, 1995TL2741>. Treatment of amidines with (diacetoxyiodo)benzeneyields either 1,3-disubstituted ureas or trisubstituted acylureas depending on the reaction condi-tions <1997JCS(P1)2319>.
6.16.1.1.8 Preparation of carbamoyl azides
The early review on carbamoyl azides <1965CRV377> indicated three preparation methods,which are still the ones most commonly used: (a) reaction of carbamoyl chlorides withsodium azide; (b) addition of hydrazoic acids to isocyanates; and (c) oxidation of semicarbazideswith HNO2. Since this review, only few reports on synthesis of the title compounds haveappeared.
The reaction of carbamoyl chlorides with sodium azide usually occurs under very mild condi-tions (aq. acetone, 0–20 �C) with carbamoyl chlorides being used as such <1987GEP252824> orprepared in situ from the corresponding amine and phosgene <1995JOC321>.
Treatment of chloroformyl <1985JOU1436> and �-chloroalkyl isocyanates <1976JOU1140>with excess of hydrazoic acid resulted in both addition to the isocyanate moiety and substitutionof the chlorine atom with the azido group affording the corresponding diazido compounds,whereas with �-chloro-functionalized isocyanates no substitution reaction was observed<1985RRC317>. The isocyanate reactant can also be generated in situ by addition of hydrazoicacid to acyl ketenes accompanied by nitrogen elimination <1981JOC147, 1981JOC153> or byCurtius rearrangement of acyl azides <1986JHC1103, 1990JOC5017>. Instead of unstable hydra-zoic acid, its derivatives, such as trimethylsilyl azide <1980JOC5130> or triarylbismuth diazides<1992JCR(S)34> could be used; however, in these reactions the mixtures of products are usuallyobtained with the product distribution depending on the reaction conditions.
Other methods for synthesis of carbamoyl azides include oxidation of aldehydes with pyridi-nium chloroformate in the presence of sodium azide <1988SC545> and reaction of carboxylicacids with the Vilsmeier salt followed by treatment with sodium azide <1994TL2729>. The latterapproach is high-yielding and applicable to the preparation of a wide variety of carbamoyl azides,including optically active substrates.
6.16.1.2 Carbonyl Derivatives with One Nitrogen and One P, As, Sb or Bi Function
6.16.1.2.1 Carbonyl derivatives with one nitrogen and one phosphorus(III) function
The most common procedure for the preparation of carbamoyl phosphines is based on thephosphine addition to alkyl or aryl isocyanates (Equation (16)) <1995COFGT(6)499>. Thereaction is tolerant to the presence of thiol <1973JPR471>, alkylthio <1988JGU1310>, andketo <1970JPR366> groups, and is applicable both to secondary and primary phosphines. In thelatter case, however, double carbamoylation of the phosphine occurs <1988JGU28>, even forsterically hindered phosphines.
P HR2
R1
N C OR3
P N
OR3
H
R1
R2
+ ð16Þ
The bulky analog of PH3, tris(trimethylsilyl)phosphine (tris(TMS)phosphine), gives with iso-propyl isocyanate exclusively 1:1 adduct 30, which exists in equilibrium with its (siloxy)iminetautomer 31 (Equation (17)) <1989AG(E)53>. Under mild conditions, isocyanates readily insertinto the Zr�P bond of PH-functionalized zirconocene complexes 32 to afford the corresponding(phosphinoamidato)zirconocenes 33 in 81–85% yields (Equation (18)). The presence of a bulkyligand, such as R1= �5-C5EtMe4, favors the formation of complexes 33 exclusively as endo-isomers (shown), whereas products 33 with less sterically hindered ligands e.g., R1= �5-C5MeH4, were formed as mixtures of endo- and exo-isomers, with exo-isomers predominating<2000OM2445>. To our knowledge, up to the early 2000s, this reaction represents the onlyprocedure for the preparation of a secondary carbamoyl phosphine in acceptable yields.
468 Functions Containing a Carbonyl Group and Two Heteroatoms
P(TMS)3 N C OPri Et2O, rt
P N
OPri
TMS
TMS
TMSP N
PriTMS
TMS
OTMS+
3 days+
30 31
ð17Þ
OZr
NPHR2
R3
R1R1
Cl[R12ZrCl(PHR2)] + R3NCO
R1 = (η5-C5EtMe4), R2 = cyclohexyl
R1 = (η5-C5MeH4), R2 = 2,4,6-Pri3 C6H2
R3 = i-Pr, Ph32 33
Pentane, rt
24 h
81–85% ð18Þ
The tertiary phosphine 34, bearing a suitably located boryl group, underwent addition tophenyl isocyanate followed by intramolecular heterocyclization to give the six-membered hetero-cycle 35 in 63% yield. On heating in benzene or acetonitrile, 35 readily rearranges to the bicyclicheterocycle 36 (Scheme 11) <1991BAU2099>.
Another approach to the synthesis of tertiary carbamoyl phosphines, not including the reactionwithisocyanates, is based on carbamoylation of secondary phosphines with carbamoyl chlorides. The onlyexample of such a transformation, reported up to the early 2000s, is carbamoylation of bis(trimethyl-siloxy)phosphine 37, which gave the desired derivatives 38 in moderate yields (Equation (19))<1993JGU226>.
(TMSO)2PH ClCONR2
Et3N
Et2O P NR2
OTMSO
OTMS
+
rt, 2 days37 38
52–61%R = Me, Et; R2N = morpholino, piperidino
ð19Þ
Phenylcarbamoyl phosphine 40 was obtained as the major product of hydrolysis of azaphos-phaallene 39 (Equation (20)) <1990BCJ2736>. However, the hydrolysis pathway depends dra-matically on the nitrogen substituent: for example, replacement of the phenyl group onthe nitrogen atom of 39 with a sterically hindered substituent, e.g., t-butyl, results in nucleophilicattack at the phosphorus atom rather than at the carbon, giving quite different sets of products.
P C N Ph
But
But
But
HN
Ph
H
O
But
ButBut
P
H2O
39 40
ð20Þ
6.16.1.2.2 Carbonyl derivatives with one nitrogen and one phosphorus(V) function
As in the synthesis of carbamoyl phosphines (Equation (16)), addition to isocyanates is the mostcommon procedure for the preparation of phosphorus(V)-bearing carbamoyl compounds. Asphosphorus reagents, both phosphine oxides <1983JHC331, 1991JGU622, 1995COFGT(6)499,
P
Ph Bu
BBun2
n2
PhPh
PhNCO Ph2PN
BBu
O Ph
Ph Bun
+ Ph2PNB
O Ph
Ph BunBun
+
∆+ Bun
34 35 36
C6H6, rt
Overnight
MeCN or C6H6__
Scheme 11
Functions Containing a Carbonyl Group and Two Heteroatoms 469
1996SC783, 2002HAC63> and trimethylsilylated phosphites (Equation (21)) <1987JMC1603,1990T7175, 1995COFGT(6)499> can be utilized. The latter reaction was also applied to thesynthesis of chiral phosphorus dipeptides <1987JMC1603>. The isocyanate addition can befollowed by intramolecular heterocyclization to afford the corresponding phosphaazaheterocycles<1995TL2021>. Diphosphanyl ketimine oxide 41 serves as a 1,3-dipole in [3+2]-cycloadditionreaction with phenyl isocyanate resulting in formation of azaphospholene 42 in 75% yield(Equation (22)) <2002CEJ3872>. The second, also widely used, approach is the substitutionreaction of alkoxycarbonyl or alkylthiocarbonyl phosphine oxides and phosphonates with nitro-gen nucleophiles (Equation (23)). The reaction proceeds smoothly with ammonia<1986JMC1389, 1995COFGT(6)499>, primary amines <1988JGU26, 1998SL1325>, aminoacids <1998SL1325> and diamines <2000HAC470>, and even with hydroxylamines<1997JOC3858>, although in the latter case the reaction has to be carried out in pyridine toavoid formation of the Lossen rearrangement product. A variety of functional groups, such asalcohols, esters, or amides, is tolerated.
POTMSEtO
OEtRNCO+ P N
EtO
OEt
R
H
O
O
R = Ph, 87%R = 4-O2NC6H4, 86%
CH2Cl2, rt
ð21Þ
C C N PhP
P
PhPh
OPhPh
+ PhNCOP
N
NPh
O
PPh
OPh
Ph
PhPh
41 42
Toluene
reflux, 10 min
75%
ð22Þ
P
O
XR1
R2O
P
O
NR3R4R1
R2O
R3R4NH
X = OMe, SEt, OPh
ð23Þ
P-Carbamoylation of 3-bis(siloxy)phosphinyl propanoate 43 under mild conditions with simul-taneous elimination of TMSCl gave the functionalized carbamate 44 in 87% yield (Equation (24))<1996JGU1867>.
ClCONMe2 PTMSO
O
OTMSO
O NMe2CH2Cl2OTMS
TMSOO
OTMSP
43 44reflux
87%
ð24Þ
Studies on azide addition/Schmidt rearrangement of dialkyl acylphosphonates RCOPO(OR0)2revealed the formation of carbamoyl phosphonates RNHCOPO(OR0)2 as the primary rearrange-ment products <1994JA1016>. However, the yields of these compounds depend on the substitu-tion in the starting acyl phosphonate and usually do not exceed 20%, making this approachineffective for the synthesis of carbamoyl phosphonates.
6.16.1.2.3 Carbonyl derivatives with one nitrogen and one arsenic function (carbamoyl arsines)
No information on the synthesis of tertiary carbamoyl arsines has been found in the literature.The data on secondary carbamoyl arsines are essentially limited to the single early article<1967LA248>, already reviewed <1995COFGT(6)499>, which reported the preparation ofthese compounds via Sn-catalyzed addition of alkyl, cycloalkyl, and aryl arsines or their lithiumderivatives to phenyl or cyclohexyl isocyanates.
470 Functions Containing a Carbonyl Group and Two Heteroatoms
The heterocycle 46, which could be considered as pyridine-fused cyclic carbamoyl arsine,existing, however, exclusively in the hydroxy form shown (Scheme 12), was prepared in a lowyield by treatment of zwitterionic pyridooxadiazole 45 with tris(trimethylsilyl)arsine followed byhydrolysis <1988TL3387>.
6.16.1.2.4 Carbonyl derivatives with one nitrogen and one antimony function
No compounds of this type have been found in the literature.
6.16.1.2.5 Carbonyl derivatives with one nitrogen and one bismuth function
A single article, dealing with this class of compounds, reported the formation of quaternarycarbamoyl bismuthanes on treatment of dimethylformamide-BiCl3 adduct with tertiary amines<1995COFGT(6)499>. To our knowledge, no more data on such compounds has appeared in theliterature since.
6.16.1.3 Carbonyl Derivatives with One Nitrogen and One Metalloid (B, Si, Ge) Function
6.16.1.3.1 Carbonyl derivatives with one nitrogen and one boron function
Carbamoyl boranes are generally prepared as adducts with tertiary amines, such as trialkylamines, pyridine, or quinuclidine, via two synthetic approaches based either on amidation ofamine-carboxyborane adducts or on hydrolysis of amine-cyanoboranes. Thus, direct couplingof trimethylamine-carboxyborane 47 with primary or secondary aliphatic or primary aromaticamines in the presence of the peptide-condensing agent dicyclohexylcarbodiimide (DCC) gave thecorresponding carbamoylborane adducts 48 in moderate yields (Equation (25)) <1987JCR(S)368,1990BCJ3658, 1995COFGT(6)499>. A similar procedure was applied to the synthesis of theboron analog of hydroxamic acid using hydroxylamine hydrochloride in water instead of anamine <1988IC302>.
Me3N BH2COOH Me3NDCC
CH2Cl2R1R2NH. BH2CONR1R2
rt, 3 days
.+
47 48
60–70%
ð25Þ
The other general approach is based on a two-step procedure including addition of triethyl-oxonium tetrafluoroborate to cyanoborane adducts followed by basic hydrolysis of the inter-mediates 49 (Scheme 13).
NN
O
O
NN
As
OH_
i. (TMS)3As, MeCN18%
ii. MeOH, 2 h
82%
45 46
+
Scheme 12
A BHRCN A RHB NHEt
O
RHB C N Et+
BF4.. .
– aq. NaOH
49
–
50–99%
Et3O+ BF4A
Scheme 13
Functions Containing a Carbonyl Group and Two Heteroatoms 471
Both unsubstituted (R=H) <1990IC554, 1990IC3218, 1991T6915> and monosubstituted(R=Me, i-Pr, i-Bu, s-Bu, Bn) cyanoboranes <1989CC900, 1989IS79, 1991IC1046> could be used,whereas the second component (A) of the adduct could be a tertiary amine<1989CC900, 1990IC554,1991IC1046>, triethyl phosphite <1991T6915>, or phosphonate <1990IC3218>. The similar treat-ment of amine-dicyanoborane adduct afforded amine-bis(carbamoyl)boranes <1997CC1799>.
Limitation of the above method to the preparation of ethylcarbamoyl boranes due to exclusiveapplication of triethyloxonium tetrafluoroborate triggered a search for other synthetic proce-dures, which up to the early 2000s have been represented by single examples. Thus, addition ofSbCl5 to Me3N�BH2CN followed by treatment with t-butyl chloride and basic hydrolysis givest-butylcarbamoyl borane adduct <1994POL2599>.
Cyanation of diboratacyclohexane 50 with isonitrile 51 resulted in formation of the bridged saltproduct, which on hydrolysis with aq. NaOH gave N-unsubstituted carbamoyl boracycle 52(Scheme 14) <1991IC2228>.
Reaction of pyridine-cyanoborane adduct 53 (R=CN) (Figure 2) with methyl triflate at 40 �Cin the absence of light gave the carbamoylborane adduct 53 (R=MeNHCO) in 19% yield<2000S1229>. On stirring in methanol at room temperature (rt), the monomeric adduct oftriphenylborane with 2-(trimethylsiloxy)phenyl isocyanide undergoes dimerization/rearrangementto afford heterocyclic diborane 54 in 20% yield <1996OM1251>.
6.16.1.3.2 Carbonyl derivatives with one nitrogen function and one silicon function (carbamoyl silanes)
Since the early report on the preparation of the first thermally stable carbamoyl silaneMe3SiCONEt2 by silylation of dicarbamoyl mercury with hexamethyldisilathiane<1995COFGT(6)499>, several approaches to the construction of the N�CO�Si link have beendeveloped, most of which, however, are applicable exclusively to tertiary carbamoyl silanes andsuffer from severe limitations. Up to the early 2000s unstable secondary carbamoyl silanes havebeen prepared only by hydrosilylation of isocyanates either with t-BuPh2Li at �50 �C<1983T2989> or with Et3SiH in the presence of PdCl2 <1977JOM(140)97>.
Tertiary carbamoyl silanes 56, bearing a sterically hindered aryl group at the nitrogen atom,have been prepared, albeit in low yields, via carbonylation of lithiated silyl amides 55, generatedin situ from the corresponding anilines and chlorosilanes, accompanied by 1,2-Si rearrangement(Scheme 15) <1994OM1533>.
Me3N.H2B–N C+ _N
B N
BMe
Me
MeMe
I
H
H
H +
+i. CHCl3
N
B N
BMe
Me
Me Me
HNH2
O
H
H
+
++
rt, 2 days
ii. aq. NaOH
50 51 5280%
_
_ _
_
Scheme 14
NB
R
S
S
HH+
_
N+
O
SiMe3TaCp*Cl3
NB
O
BO
Ph Ph
NOHHPh Ph
++
53 54
_
58
_
_
Figure 2 Examples of carbamoyl boranes and silanes.
NLi
SiR3
ArN
O
SiR3
Me
Ari. CO (30 atm.) rt, 15 min
ii. MeI,
R3 = Me3, PhMe2
Ar =2,6-R′2C6H3 (R′ = Me, Et, i-Pr)
17–40%55 56
–78 °C
Scheme 15
472 Functions Containing a Carbonyl Group and Two Heteroatoms
Silanes 56 could also be synthesized by sequential introduction of the carbonyl and trimethyl-silyl group via carbonylation of mixed cuprates followed by silylation with a chlorosilane<1994JOM(474)23>.
Lithiation/silylation of formamide HCON(Me)CH2OMe afforded the corresponding carbamoylsilane Me3SiCON(Me)CH2OMe 57 in 61% yield <2001TL1423>. Although only the trimethylsilyl(TMS) group could be directly introduced by this procedure, a series of carbamoyl silanes were preparedvia silyl group exchange by treatment of 57 with chlorosilanes at 145 �C in the presence of CsF.
Although the synthesis of carbamoyl silanes by silylation of carbamoyl chlorides seemsobvious, the preparation of silanes (TMS)3SiC(O)NR2 (R=Me, Ph) from carbamoyl chloridesR2NCOCl and (TMS)3SiLi(THF)3 still represent the only example of such a transformation<1991JOM(403)293>.
Carbonylation of Cp*Cl3TaSiMe3 with limited quantities of CO followed by addition of pyridineor 2,6-dimethylpyridine gives the stable Ta-carbamoyl silane complex e.g., 58 (Figure 2), bearing aquaternary nitrogen atom <1989JA149>.
6.16.1.3.3 Carbonyl derivatives with one nitrogen and one germanium function (carbamoylgermanes)
In contrast to the silicon analogs, only one example of synthesis of carbamoyl germanes usingtrialkylgermyl chloride has been reported up to the early 2000s <1971AG(E)339>. All the otherknown procedures use Et3GeLi as the germanium-introducing reagent. Thus, reaction of Et3GeLiwith CF3C(O)NEt2 <1983JOM(248)51> or Me3Si�C�C�C(O)NMe2 <1984BAU1733> underthermodynamic control conditions afforded carbamoyl germanes Et3GeC(O)NEt2 (56%) andEt3GeC(O)NMe2 (45%), respectively.
The scope of the carbamoyl group-delivering reagents has been extended to carbamates(Equation (26)) <1990POL227>. Me2NCOCl could also be used in this reaction as a carbamoyl-ating reagent; however, in this case only 0.25 equiv. of the aluminum alkoxide should be employeddue to its rate-inhibiting effect.
XN OMe
O
XN GeEt3
O
Et3GeLi
70–80 °C
+
3 h
(sec-BuO)3Al (1 equiv.)
X = O, 54%X = CH2, 33%
Hexane / benzene ð26Þ
6.16.1.4 Carbonyl Derivatives with One Nitrogen and One Metal Function
6.16.1.4.1 Carbon monoxide insertion reactions
One of the most widely used methods for the preparation of carbamoyl metal complexes is based onthe insertion of the carbon monoxide molecule into an already existing nitrogen�metal bond(Equation (27)). The examples of organometallic compounds involved in the transformation include:cuprates<1985JOM(297)379>, complexes of nickel<2002CC1840>, iron<1992JA1256>, platinum<1985OM939>, palladium <2000OM1661>, rhodium <1988OM2234, 1992IC379>, iridium<1994OM1751>, ruthenium <1993IC3640, 1999OM187>, rhenium <1998OM131>, molybdenum<1987OM210>, tungsten <1986OM185>, thorium, and uranium <1988CRV1059,1995COFGT(6)499>. Molybdenum or copper complexes containing more than one metal�nitrogenbond, such as Mo(NMe2)4 or lithium bis(amino)cuprates, undergo CO insertion into all these bondseven under mild reaction conditions. In contrast, carbonylation of tungsten complex W2Cl2(NMe2)4with excess of CO in toluene/pyridine gave exclusively the monoinsertion product in 69% yield<1986OM185>.
M NR2(L)n M NR2
O
(L)nCO ð27Þ
Functions Containing a Carbonyl Group and Two Heteroatoms 473
1,3-Dipolar cycloaddition reactions of (1,4-diaza-1,3-butadiene)tricarbonyliron complexes 59(M=Fe) (Equation (28)) with electron-deficient alkynes, such as dimethyl acetylenedicarboxylate(DMAD) or methyl propiolate, in the presence of an external ligand L [L=CO, P(OMe)3] isaccompanied by intramolecular insertion of a CO molecule into the metal�nitrogen bondaffording thermally labile bicyclo[2.2.1] adducts 60 in 60–95% yields <1985OM948,1986JOM(302)59, 1987JOM(323)67, 1990OM1691, 1996OM2148>.
++
N
M
NR
R
COCO
CO
59
M = Fe, Ru
R = i-Pr, t-Bu
R2R1
R1 = R2 = CO2Me
R1 = H, R2
= CO2Me
LOCR1
R2
N
MN
O
R
R
CO
60
60–95%
L
ð28Þ
Analogous reactions of ruthenium complex 59 (M=Ru, R= i-Pr) with DMAD in the pre-sence of CO or PPh3 as external ligands have been observed <1992OM3607>. In contrast to theiron analogs, which are unreactive toward electron-deficient alkenes, ruthenium complexes 59(M=Ru; R=Me, i-Pr) undergo cycloaddition with dimethyl maleate or fumarate to afford thecorresponding adducts in 70–90% yields <1995OM4781>.
6.16.1.4.2 Aminative carbonylation
Another widely used procedure for the preparation of carbamoyl metal compounds is based onthe introduction of both carbonyl and amine moieties into the organometallic compound and isgenerally performed by carbonylation of a metal complex in the presence of a primary or asecondary amine. Although most commonly used in the synthesis of platinum and palladiumcarbamoyl compounds <1985JOM(296)435, 1987JOM(334)C9, 1990OM2603, 1990OM2612,2000OM3879, 2002MI267>, this approach has also been applied to the preparation of carbamoylstannanes <1988JCS(P1)569>, nickel <1985AG(E)325, 1985JOM(281)379>, rhodium<1993OM3410>, ruthenium <1998JOM(563)1>, and iron <2000OM3754> complexes.
A modification of this procedure includes carbonylation of metal complexes in the presenceof nitrobenzene as an amine precursor <2000OM3754, 2002MI267>; however, this reactionrequires significantly higher temperatures (80–160 �C) compared to the one using amines (0 �C–rt).
Indirect aminative carbonylation is represented by the reaction of Ph3PAuCl with methyl iso-cyanide in aq. KOH, which afforded the unstable carbamoyl gold complex Ph3PAuC(O)NHMe,presumably via hydrolysis of the intermediate isonitrile gold complex <1999IC3494>.
6.16.1.4.3 Amination
Currently, amination of metal carbonyl complexes represents the most common approach to thepreparation of metal carbamoyl derivatives and has been successfully applied to the synthesisof carbamoyl complexes of Re <1988JOM(339)111, 1997JOM(541)423>, Mo <1989IC4414,1991OM1305, 1997OM5595>, Ir <1992JOM(441)155>, Os <2002JOM(658)147, 2002MI963>,Fe <1991IC1955, 1993OM1725, 1994CB711, 1996JCS(D)4431, 1997HCA121, 1999ZN(B)385,2000OM15>, Mn <1991JOM(414)65>, Pd <1989OM2065, 1990JOM(383)587>, Ru<1984IC4640, 1986ICA169, 1989JOM(368)103, 1989JOM(379)311, 2001OM3390>, Co<1986OM2259, 1987CB379>, Cr <2001ZN(B)306>, W <1994OM1214, 1999OM748,2001ZN(B)306>, and Pt <1985OM180, 1988JA7098, 1991OM175>. Both neutral metal com-plexes (for Mo, Ir, Os, Pt, Mn, Ru, Fe) and cationic complexes (for Fe, Pd, Co, W, Pt, Re) couldbe used. The reactions can be accompanied by the loss of a nonreacting ligand <2002MI963>.
As nitrogen nucleophiles, both primary <1991JOM(414)65, 1992JOM(441)155> and secondaryaliphatic amines <1988JA7098, 2002JOM(658)147>, cyclic amines <1988JOM(339)111,1989JOM(368)103, 1990JOM(383)587>, aryl alkyl amines <1986ICA169>, anilines
474 Functions Containing a Carbonyl Group and Two Heteroatoms
<1986OM2259>, amino esters <1999ZN(B)385>, hydrazines <1991IC1955, 1991OM1305> andeven N-substituted aziridines (with aziridine ring opening) <1997HCA121>, and N-nitrosoamines<1993OM1725> were applied. An aromatic amine could also be generated in situ from the correspond-ing nitroarene under reductive conditions <2001OM3390>.
In a metal complex with a ligand bearing a suitably located nucleophilic nitrogen atom,intramolecular amination can occur <1990JOM(387)C5, 1996JCS(D)4431>. The outcome ofthe reaction with diamines is determined by the starting organometallic compound: thus, cationic(OC)5ReFBF3 reacts with both amino groups of diaminoalkanes in a standard fashion affordingthe corresponding dicarbamoyl-bridged 2:1 complexes <1988JOM(339)111>, whereas monoami-nation of (OC)5ReOSO2CF3 is followed by intramolecular attack of the second amino group atthe central metal atom with formation of the cyclic carbamoylrhenium complex<1997JOM(541)423>.
Tetrakis(dimethylamino)methane, C(NMe2)4, has also been used as an efficient dimethylaminogroup donor for the preparation of Ru <1984IC4640>, Cr and W <2001ZN(B)306> carbamoylcomplexes under mild conditions. The reaction proceeds via insertion of one of the carbonyls of themetal carbonyl compound into the C�N bond of the tetraaminomethane. A procedure based on asimilar mechanism was applied for the preparation of a series of bimetallic complexes. Thus, reactionof carbonyl complexes M(CO)n (M=Fe, n=5; M=Cr, Mo, W, n=6) or Mn2(CO)10 withorganometallic dimethylamides, such as Al(NMe2)3 <1987JOM(323)149>, Ti(NMe2)4<1993JOM(456)85>, Zr(NMe2)4 <2000JOM(598)403> or Cp*M0(NMe2)3 (M0=Ti, Zr)<1995OM131>, gives the corresponding heterogeneous cluster compounds with M-CO-N fragment.
6.16.1.4.4 Reactions with heterocumulenes (isocyanates, ketenimines, azides, carbodiimides)
Reactions of neutral or cationic metal carbonyl complexes with isocyanates occur under mildconditions (neutral solvents, rt) and result in formation of the corresponding metallacyclic 1:1adducts with a cycle size depending on the central metal and on the nature and reactivity ofthe ligands in the original complex. Thus, Cp2W(CO) gave four-membered metallacycles<1987JA2173, 1989JA7424> and Cp2V(CO) yielded six-membered metallacycle<1988JGU2384>, whereas five-membered metallacycles 62 (X=S) were obtained from cationicFe and Ru complexes 61 and isothiocyanates (Equation (29)) <1998JOM(568)241>. Analogousreactions of the neutral complex (OC)2CpFePH(t-Bu) with isocyanates and isothiocyanatesprovided 62 [X=O, S; R1= t-Bu, R2=R3NHC(=X)] <1998JOM(568)247>.
OCM P
R1
H
CpOC R2 A
+_ PM
N
CpOC
R1
R2
O
R3
Xt-BuOK
6162
M = Fe, Ru; X = S; A = BF4, PF6;
R1, R2 = i-Pr, t-Bu, Ph; R3 = Me, Et
R3NCX
toluene, rt
68–83%
ð29Þ
This approach has also been applied to the preparation of cyclic carbamoyl mononuclearmanganese <1999OM2459>, cobalt <1991JOM(413)379>, iron <1987IC973> and binucleariron <1989OM443>, iridium <1988JA8543>, and rhenium <1999OM2459> complexes. Potas-sium cyanate was utilized in the synthesis of five-membered carbamoyl platinacycle <1989G301>.
1,3-Cycloaddition of (�5-MeC5H4)Mn(CO)2(THF) or Cp2Mo2(CO)4 with benzyl or aryl azidesgave the corresponding binuclear adducts e.g., 63 (Figure 3) <1986OM894, 1987OM2151>.Cluster Os3(CO)11(NCMe) reacted similarly <1987OM2151>, whereas reactions of cobalt andrhenium phosphine complexes CpM(CO)PR3 (M=Rh, R= i-Pr; M=Co, R=Me) occurred viaazide degradation followed by [2+1] cycloaddition to give metallaaziridinones 64 (R0=Ph, Ts)(Figure 3) in 69–79% yields <1992JOM(440)389>.
Metal carbonyl anions [CpFe(CO)2]� and [Re(CO)5]
� undergo regiospecific [2+2] cycloaddi-tion with ketenimines R1R2C¼C¼NR3 (R1=R2=Ph; R3=Me, Ph) to give the isolableanionic complexes e.g., 65 (Figure 3) <1985JOM(294)251>. Under similar conditions, the carbeneiron complex (CO)4Fe¼C(OEt)Ph afforded acyclic �-allyl,�-complexes 66 (R1=Me, Et, i-Pr;R2=Me; R3=Ph) <1991CB1795>.
Functions Containing a Carbonyl Group and Two Heteroatoms 475
The reaction of Cp2W(CO) with diphenyl carbodiimide occurs by the same route as its reactionwith isocyanates to give [2+2]-cycloaddition product, imino-substituted metallaazetidinone, in 94%yield <1989JA7424>. A similar formation of formal [2+2]-cycloaddition products was observed inthe reactions of CpW(CO)3H and Cp*W(CO)3H with acyclic or cyclic sulfur diimides<1985ZN(B)1233, 1989JOM(371)303, 1993CB1781>. The reactions are regioselective: in the caseof monosubstituted sulfur diimides, only substituted nitrogen atom participates in the metallacycleconstruction. When sulfur diimides with electron-accepting substituents, such as Ts, were used, nocyclization was observed and only acyclic metal�hydrogen bond insertion products were isolated.
6.16.1.4.5 Miscellaneous reactions
(i) Additions of metal carbonyls to iminophosphines and phosphine imides
Treatment of Fe or Mo carbonyl complexes with iminophosphines results in ligation of thephosphorus to the metal atom followed by intramolecular attack of imine nitrogen at a CO ligandto afford the corresponding metallaphosphaazetidinones <1985JA2553, 1986OM2376>. In con-trast, the analogous reactions with phosphine imides are accompanied with the cleavage of thephosphorus�nitrogen bond giving metallapyrrolinone complexes in 69–72% yields <1991JA3800>.
(ii) Transmetallation
Platinum and palladium carbamoyl complexes (Et2NCO)M(PPh3)2X (M=Pt, Pd, X=Cl;M=Pt, X=PPh3) were prepared in 75–87% yields by treatment of carbamoyl mercury com-pounds ClHgCONEt2 or Hg(CONEt2)2 with Pt(0) or Pd(0) triphenylphosphine complexes at20 �C in benzene <1980BAU1490>.
(iii) Ligand modification reactions
Treatment of transition metal complexes bearing an alkoxycarbonyl ligand with primary aliphaticor benzylic amines under mild conditions results in substitution of the alkoxy group with analkylamino fragment. The reaction was applied to the preparation of Ru <1994IC253>, Re<1992IS211> and Fe <1985JCS(P1)2375, 1985T5871> carbamoyl complexes.
6.16.2 FUNCTIONS CONTAINING AT LEAST ONE PHOSPHORUS, ARSENIC,ANTIMONY, OR BISMUTH FUNCTION (AND NO HALOGEN, CHALCOGEN,OR NITROGEN FUNCTIONS)
6.16.2.1 Carbonyl Derivatives with Two P, As, Sb, or Bi Functions
One of the few approaches to the preparation of carbonyl compounds with two phosphorusfunctions is based on the modification of the substituents on the central carbon of the alreadyexisting P�C�P fragment. Thus, the parent carbonylbis(phosphonic) diacid was prepared in
Me
Me
Re N Ph
O
Ph Ph
(OC)4N
N
MnN
MnCO
O
OC
Ph
CO
M
NO
R′
Cp
R3PR1
R2 CO2EtPh
N R3
O(OC)3Fe
63 64 65 66
_
Figure 3 Carbamoyl metal complexes.
476 Functions Containing a Carbonyl Group and Two Heteroatoms
63% yield by basic hydrolysis of its dichloro derivative <1995COFGT(6)499>; however, thisprocedure is restricted to this particular compound. Later, a series of carbonylbis(phosphonates)68 (Equation (30)) was prepared by McKenna and co-workers by oxidation of the corresponding�-diazomethylenebis(phosphonate)s 67 with t-BuOCl. The product yields and formation of�,�-dichloro-substituted by-products depend on a solvent and the presence of water, with aq.EtOAc being preferred as a solvent <1993PS(76)139, 1999PS(144)313, 2000WOP002889>.
t-BuOCl
aq. EtOAc
2–5 min
10–15 °C
P PO
OR
N2
O
ORORRO
67
P PO
OR
OO
ORORRO
68
R = Me (93%), Et (94%) i-Pr (95%)
ð30Þ
Another approach is based on the reaction of phosphines or their trimethylsilyl derivatives withphosgene. In this reaction, the secondary phosphines give acyclic carbonyldiphosphines<1995COFGT(6)499>, whereas primary phosphines and their silylated analogs afford four- orfive-membered phosphacycles (Scheme 16) <1983CB109, 1983TL2639, 1999ZAAC1979>, pre-sumably via dimerization of phosphaketene intermediates.
The formation of intermediate bis(phosphaketene) was also suggested for the preparation ofanionic heterocycle 69 (Figure 4) by treatment of P�C�OLi with SO2 in dimethoxyethane(DME) at �50 �C <1995ZAAC34>.
Carbonylation of homoleptic eight-coordinated thorium dialkylphosphideTh[P(CH2CH2PMe2)2]4 in hydrocarbons afforded the double insertion product 70 (Figure 4) in73% yield <1994CC1249>. The similar carbonyl bridge formation between phosphorus ligandswas observed in reactions of sterically hindered (dialkylamino)dichlorophosphines with tetracar-bonyl ferrate as the carbon monoxide source <1995COFGT(6)499>. The mechanism of thistransformation, steric requirements, and substituent effects have been studied in detail<1990JOM(383)295>.
Organometallic compounds bearing a P�CO�P unit were also prepared via carbonylative P�Pbond cleavage of metal diphosphine complexes. Thus, cleavage of the P�P bond with insertion ofcarbon monoxide was observed on treatment of iron complexes 71 or 72 with CO or excessFe2(CO)9 (Scheme 17) <1986ZN(B)283, 1991CB265> or by ring opening–ring closure of sub-stituted cyclotetraphosphane in the presence of Fe2(CO)9 <1991CB265>.
COCl2PP
O
O
R R t-BuP(TMS)2Ph3CPH2 Et2O
COCl2
rt, 18 h–60 °C
94% R = t-Bu or Ph3C
Scheme 16
ThOP
Me2P
PMe2
C
PMe2P C
PPMe2
PMe2
PMe2
Me2P
PO
Me2P
70
–O
PP
P
P O
O O–
69
Figure 4 Polycyclic phosphacarbonyl compounds.
Functions Containing a Carbonyl Group and Two Heteroatoms 477
Cleavage of the phosphorus�phosphorus double bond followed by carbon monoxide insertionon treatment of a series of Fe, Ru, or Os diphosphene complexes with excess of Fe2(CO)9 intoluene affords the corresponding metallated diphosphinomethanone complexes, analogs of 73<1986AG737, 1987CB1421>.
No information on the synthesis of carbonyl derivatives with two As, Sb, or Bi functions, orunsymmetrical analogs has been found up to the early 2000s.
6.16.2.2 Carbonyl Derivatives with One Phosphorus and One Metal Function
The most important approaches to the preparation of carbonyl compounds with one phosphorusand one metal function are based on: (a) carbon monoxide insertion into the metal�phosphorusbond; (b) formation of P�CO bond via phosphinylation of metal carbonyls; (c) formation of theM�CO bond via reaction of metal complexes with �-keto phosphonates; and (d) carbonylativephosphinylation of metal complexes.
The carbonylation approach has been successfully applied to the preparation of hafnium<1988CRV1059, 1995COFGT(6)499>, thorium 70 (Figure 4) <1994CC1249>, and zirconiumcomplexes <1996OM1134> under mild conditions.
A series of phosphinocarbonyl complexes 75 was synthesized by reaction of cationic complexes74 with the corresponding lithium phosphides (Equation (31)) <1985CB1193, 1985OM2097>.The polarity of the reagent can also be reversed: thus, anionic bimetallic complex(Cp�Li+)(CO)3MoCo(CO)4 readily reacted with chlorodiphenyl phosphine to give Mo2Coproduct with a carbonyl bridge between phosphorus and cobalt atoms <2000JOM(607)156>.
OCMCp*
O
PR2
R1
OCEt2OLiPR1R2[Cp*M(CO)3]+BF4
_+
30 min74 75
M = Fe, Ru
R1, R2 = TMS, t-Bu
–78 to 0 °C
ð31Þ
Neutral phosphines and phosphites were also applied for phosphinylation of carbonylcomplexes of molybdenum <1987OM1587>, iridium <1993JCS(D)1031>, and tantalum<1987IC2556>.
Reaction of Ni(COD)2 with �-keto phosphonates in the presence of PPh3 affords �2-COcoordinated complexes 76 (Equation (32)) <1990OM1958>.
R
O
POMe
OOMe
NiPh3P
Ph3PNi(COD)2
PPh3R
O
POMe
OOMe Et2O
+
76rt
R = Me (79%), Et (89%), Ph (73%), 4-ClC6H4 (65%), 4-MeC6H4 (72%)
ð32Þ
P(OC)3Fe Fe(CO)3
PBut But
P(OC)3Fe Fe(CO)3
PR But
CO Fe2(CO)9
THF(OC)3Fe Fe(CO)3
PPR But
O
Benzene
80 °C, 20 h rt, 2 days
71 72
R = t-Bu, Cp*Fe(CO)2
75%R = Cp*Fe(CO)2
44%73
Scheme 17
478 Functions Containing a Carbonyl Group and Two Heteroatoms
Treatment of Cp*Cl3TaSiMe3 with trialkyl phosphines or phosphites under CO atmosphereresults in carbonylative phosphinylation of the tantalum complex to give adducts 77 (Figure 5)<1987IC2556, 1989JA149>, whereas carbonylation of zirconocenes bearing a phosphine-functionalized cyclopentadiene ring affords intramolecular phosphinylation products 78<1991OM2266, 1995OM1525>.
6.16.2.3 Carbonyl Derivatives with One B, As, Sb, or Bi Function, and One Metal Function
The reaction of 9-o- or 9-m-carboranecarbonyl chlorides with NaRe(CO)5 in THF at �70 �C gavethe corresponding Re-complexes C2H2B10-CORe(CO)5 in 58–67% yields <1987BAU1486>.
The transmetallation of solvated lithium complex of arsadionate 79 using RuCl2(PPh3)3 in DMEafforded the Ru complex 80 with not fully delocalized arsadionate ligand (Equation (33))<2001JCS(D)3219>. In contrast, the analogous reactions with FeCl2 or CoCl2 gave the complexeswith planar arsadionate ligands, coordinated to the metal center in a chelating �2-O,O-fashion.
O O
As ButBut
LiO
Li
As
O
But But
O O
As ButBut
RuCl
PPh3PPh3
RuCl2(PPh3)3
79 80
DME,
73%
–78 °Cð33Þ
No data on the preparation of carbonyl compounds with one Sb or Bi, and one metal functionhave been reported up to the early 2000s.
6.16.3 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION (ANDNO HALOGEN, CHALCOGEN, OR GROUP 5 ELEMENT FUNCTIONS)
6.16.3.1 Carbonyl Derivatives with Two Silicon Functions
Two major approaches to the preparation of symmetrical bis(silyl) ketones involve C¼O bondformation in the pre-existing Si�C�Si fragment and are based on oxidation and hydrolysisreactions. Since the early synthesis of bis(triphenylsilyl) ketone via oxidation of the correspondingalcohol <1995COFGT(6)499>, the efforts were concentrated mostly on the preparation of thesimplest representative of this class, bis(trimethylsilyl) ketone.
In the oxidative approach, (Me3Si)2CO 83 (Scheme 18) was readily prepared via ozonation ofbis(silylated) ylide 81 <1995COFGT(6)499, 1995LA415> or by oxidation of trimethylsilyl deri-vative 82 with m-chloroperbenzoic acid (MCPBA) <1995COFGT(6)499>.
R2
R3P
CO
SiMe3
Ta
+
Cp*Cl3 ZrR1
C
O
PPh2
Me
Ru
RuOC
C
C
R2
R1
Cp*
Cp*
_
77
R = Me, Et, OMe
R1 = Cl, Me; R2 = H, PPh2
78 92
R1 = Me, Et; R2 = H, Me
+
–
Figure 5 Examples of carbonyl compounds with one phosphorus and one metal or two metal functions.
O3 P(OPh)3.
C PPh3TMS
TMSO
TMS
TMSSMeTMS
TMSTMS
CH2Cl281 8283Toluene
45%30–50%
MCPBA
–78 °C –78 °C
Scheme 18
Functions Containing a Carbonyl Group and Two Heteroatoms 479
In the hydrolytic approach, preferred due to oxidizability of 83, �-halo ethers 85, prepared bycleavage of O,S-acetal 84 with Br2 or SO2Cl2, readily hydrolyze on passing through a silica gel oralumina column to afford TMS2CO in 65–75% yields (Scheme 19) <1998ACS1141,1998SC1415>.
Similarly, bis(silyl)bis(methylthio) ketone 86, obtained by double lithiation/silylation ofbis(methylthio)methane, undergoes hydrolysis on treatment with HgO�BF3 �Et2O to givebis(dimethylphenylsilyl) ketone (Equation (34)) <1990CL1411>.
SMe
PhMe2Si SiMe2Ph
MeS
PhMe2Si SiMe2Ph
O
86
HgO-BF3.Et2O
56% ð34Þ
To our knowledge, no isolable unsymmetrical bis(silyl)ketones have been synthesized up to theearly 2000s, although the formation of (trimethylsilyl)(triphenylsilyl) ketone on hydrolysis of thecorresponding 2,2-disilylated 1,3-dithiane was proposed on the basis of infrared spectra<1968CJC2119>.
6.16.3.2 Other Carbonyl Derivatives with Two Metalloid Functions
The first bis(germyl) ketone, Et3GeCOGeEt3, was prepared via neutral hydrolysis of the corre-sponding 2,2-digermyl 1,3-dithiane derivative and characterized in solution <1967JA431>. Oneyear later, bis(triphenylgermyl) ketone was prepared in 73% yield by oxidation of the correspond-ing alcohol and fully characterized <1968CJC2119>. Since then, only one procedure for thepreparation of these compounds has been reported: bis(trimethylgermyl) ketone 89 (M=Ge) wassynthesized via germylation of thioacetal 87 followed by halogenation of 88 with SO2Cl2 and mildhydrolysis of the intermediate �-chloro ether on silica gel (Scheme 20) <2000JCS(P1)2677>.
Mixed (trimethylsilyl)(trimethylgermyl) ketone 89 (M=Si) was prepared similarly (Scheme 20).No data on synthesis of other carbonyl compounds with two metalloid functions have been foundup to the early 2000s.
6.16.3.3 Carbonyl Derivatives with One Metalloid and One Metal Function
The most general approach to the preparation of the silaacyl metal compounds is based in theinsertion of carbon monoxide into the metal�silicon bond. Thus, carbonylation of silyl zirconiumcomplexes 90 gives �2-silaacyl complexes 91 (Equation (35)) <1988CRV1059, 1988JOM(358)169,1995COFGT(6)499>.
PhS OMe
TMSTMS O
TMS
TMS
CH2Cl2 X OMe
TMSTMS
8384 85
Br2 or SO2Cl2
X = Cl (65%)X = Br (82%)
Silica gelpentane
ether
75–78%
Scheme 19
PhS OMe
GeMe3
PhS OMe
GeMe3Me3MMe3M GeMe3
O
87 88 89M = Si, X = Cl, 90%M = Ge, X = Br, 92%
i. t-BuLi, THF
–78 °C
ii. Me3MX
THF, –78 °C
i. SO2Cl2, CH2Cl20 °C, 30 min
0 °C, 30 min
ii. Cyclohexene
iii. Silica gel
pentaneM = Si, 53%M = Ge, 65%
Scheme 20
480 Functions Containing a Carbonyl Group and Two Heteroatoms
R1ZrCp
SiR33
R2
R1ZrCpR2
O
SiR33
CO (100 psi)
rtpentane or Et2O
90 91
R1 = Cp, Cp*; R2 = Cl, TMS
R3 = Me, TMS
71–90%
ð35Þ
Analogous products, prepared from complexes bearing disubstituted silyl moiety, have beenfound to be unstable <1989OM324>. A similar procedure was applied for the preparation of�2-silaacyl complexes of Re <1995COFGT(6)499>, Ta <1989JA149, 2002OM3108>, and Fe<1992T7629>. In the latter case Fe2(CO)9 was used as a carbon monoxide source.
No information on the synthesis of other carbonyl compounds with one metalloid and onemetal function has been found up to the early 2000s.
6.16.4 CARBONYL DERIVATIVES CONTAINING TWO METAL FUNCTIONS
Detailed information on both homonuclear and heteronuclear polymetallic clusters with a CObridging ligand can be found in the appropriate volumes of Comprehensive OrganometallicChemistry-II <1995COMCII> and in a series of yearly reviews titled ‘‘Organo-Transition MetalCluster Compounds’’, published in Organometallic Chemistry e.g., <2000MI275>, so the follow-ing survey is intended to give only a brief summary of the methods used for the preparation oftitle compounds in the period 1994–2003.
One of the most widely used approaches for the preparation of homonuclear bimetallic clusterswith a CO bridging ligand is based on reductive carbonylation of the corresponding metal halidesin ethylene glycol <1999JOM(580)117, 2003JOM(669)44>, or on the surface of inorganic oxidesor zeolites <2003CRV3707>, or carbonylation of neutral metal complexes <2002IS210>. Enals,such as crotonaldehyde or 2-pentenal, could serve as a source of bridging CO: thus, treatment of[Cp*RuCl]4 with these enals in the presence of K2CO3 gave diruthenium complexes 92 (Figure 5) in36–65% yields <1994OM2423>.
Other dirhodium and dirhenium clusters were obtained by dimerization of the correspondingmonomeric rhodium and rhenium carbonyls at room temperature or on heating<1999JOM(577)167, 2001IC2979>. Dimerization of indenyl rhenium tricarbonyl under UVirradiation was accompanied by loss of one CO ligand <1999OM1353>.
Another approach, applied to the preparation of both homonuclear and heteronuclear bime-tallic CO-bridged complexes, includes reaction of metal�metal bonded carbonyl compounds withexternal ligands, such as PPh3 <2000EJI159>, acetonitrile <2002JOM(658)117>, or alkynes<1994OM4695, 1995AJC1651, 2002OM4847>, which force one of CO ligands to changeits binding mode. Similarly, the reaction of iron carbonyls with t-BuGeH3 <1994CL293> orCp*2GaCl <2002JOM(646)247> yielded iron�iron bonded complexes containing both �-germyl-ene or �-gallium and �-CO bridges.
A similar procedure was applied to the preparation of heteronuclear clusters, such as CO-bridged Ru�Pd <2002JA5628>, Ir�Mo, Ir�W, Ir�Fe <2002ICA204>, Fe�Re, and Fe�Mncomplexes <1998OM2945, 2000OM72>.
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492 Functions Containing a Carbonyl Group and Two Heteroatoms
Biographical sketch
Olga Denisko was born in Krasnoyarsk, Russia and studied at MoscowState University, Russia, where she obtained her Ph.D. in 1993 underthe direction of Professor N. S. Zefirov. During 1994–1996, she workedas a Postdoctoral Research Fellow in the Center for Heterocyclic Com-pounds, University of Florida, FL under supervision of ProfessorA. R. Katritzky, after which she returned to Russia and was employedas a Chemist in the Central Laboratory of ‘‘Krasfarma’’ Pharmaceuticals(Krasnoyarsk, Russia). In 1998, she returned to the University of Floridaas Postdoctoral Research Fellow/Group Leader. After working therefor another two years, she was employed as a Senior Research Chemistby Alchem Laboratories (Alachua, FL). In June 2002, she took up herpresent position as Assistant Scientific Information Analyst at the Che-mical Abstracts Service, Columbus, OH. Her scientific research interestsinclude various aspects of heterocyclic organic chemistry and chemistryof organosulfur compounds.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 453–493
Functions Containing a Carbonyl Group and Two Heteroatoms 493
6.17
Functions Containing
a Thiocarbonyl Group
and at Least One Halogen;
Also at Least One Chalcogen
and No Halogen
E. KLEINPETER
University of Potsdam, Potsdam, Germany
6.17.1 FUNCTIONS CONTAINING AT LEAST ONE HALOGEN 4956.17.1.1 Thiocarbonyl Halides Containing Two Halogens 4956.17.1.2 Sulfoxides of Thiocarbonyl Halides (Sulfines) 4976.17.1.3 Thiocarbonyl Halides Containing One Halogen and One Other Heteroatom 4986.17.1.3.1 Halogenothioformates, ROC(Hal)¼S 4986.17.1.3.2 Chlorothioformates, ROC(Cl)¼S 4986.17.1.3.3 Halogenodithioformates, RSC(Hal)¼S 4996.17.1.3.4 Chlorodithioformates, RSC(Cl)¼S 5006.17.1.3.5 Thiocarbamoyl halides, R2NC(Hal)¼S 5016.17.1.3.6 Thiocarbamoyl chlorides, R2NC(Cl)¼S 501
6.17.2 FUNCTIONS CONTAINING AT LEAST ONE CHALCOGEN FUNCTION(AND NO HALOGEN) 502
6.17.2.1 Thionocarbonates (O,O-Diesters of Thiocarbonic Acid) 5026.17.2.1.1 From thiophosgene 5036.17.2.1.2 From chlorothionoformates 5046.17.2.1.3 From thiocarbonyldiimidazole 509
6.17.2.2 Dithiocarbonates (Esters of Dithiocarbonic Acid) 5106.17.2.2.1 Salts of O-alkyl esters of dithiocarbonic acid (xanthates) and
bisalkoxythiocarbonyl disulfides 5106.17.2.2.2 O,S-Diesters of dithiocarbonic acid 5116.17.2.2.3 Sulfoxides of O,S-diesters of dithiocarbonic acid (sulfines) 519
6.17.2.3 Thiocarbamates (Esters of Thiocarbamic Acid) 5206.17.2.3.1 From O-alkyl or O-aryl chloroformates and amines 5206.17.2.3.2 From N,N-dialkylthiocarbamoylchlorides and alcohols or phenols 5216.17.2.3.3 From N,N 0-thiocarbonyl diimidazole and alcohols 5216.17.2.3.4 From thiophosgene and 1,2-amino alcohols 5216.17.2.3.5 From CS2 and 1,2-amino alcohols 5226.17.2.3.6 From isothiocyanates and alcohols 5236.17.2.3.7 N-acyl-1,3-oxazolidine-2-thiones as auxiliary agents 5286.17.2.3.8 By thermal conversion of 2-allyl thiobenzothiazoles 5286.17.2.3.9 Other methods 528
6.17.2.4 Dithiocarbamates (Esters of Dithiocarbamic Acid) 5306.17.2.4.1 Alkali metal salts of N,N 0-disubstituted dithiocarbamic acid (dithiocarbamates) 530
495
6.17.2.4.2 Esters of dithiocarbamic acids 5306.17.2.4.3 Bis-[thiocarbamoyl](thiuram)disulfides 534
6.17.2.5 Trithiocarbonates (Esters of Trithiocarbonic Acid) 5346.17.2.5.1 Salts of monoesters of trithiocarbonic acid 5346.17.2.5.2 Diesters of trithiocarbonic acid 534
6.17.1 FUNCTIONS CONTAINING AT LEAST ONE HALOGEN
6.17.1.1 Thiocarbonyl Halides Containing Two Halogens
All four thiocarbonyl halides with identical halogens are known and were synthesized prior to1995 (see Table 1 for characteristic properties). Thiocarbonyl diiodide is the only one that has notbeen isolated, due to its labile nature, thus far and its identification has been based on IR. Thesecompounds tend to polymerize easily <1974MI25> and their stability is dependent on both thecharacter of the C¼S double bond and the donor activity of the attendant halogens<1976CB3432>. As acid halides, they react readily with alcohols, amines, etc., to yield thecorresponding carbonic acid derivatives in high yields. Some thiocarbonyl halides with dissimilarhalogens have also been synthesized and are included in Table 1. Caution! Thiocarbonyl halidesmust be handled with great care as they are highly toxic and it is imperative that exposure byingestion, inhalation, or direct absorption through the skin be avoided. As a minimum precau-tion, all operations should be conducted in a well-ventilated fume hood.
The syntheses of the thiocarbonyl halides have been extensively reviewed in COFGT (1995),and the references for the most useful syntheses are collected in Table 1. The most convenientsynthesis of thiophosgene (Cl2C¼S) is by the reduction of perchloromethylsulfenylchloride(Cl3CSCl) with H2S at 110–114 �C <1974S26>; other reducing agents have also been used.Alternatively, trichloromethyl thiol (Cl3CSH) can be reduced with SO2 in the presence of KIand S2Cl2 <1983HOU(E4)408> to provide thiophosgene (Scheme 1).
The other three symmetric thiocarbonyl halides are, in fact, available by the direct derivatizationof thiophosgene. However, the most useful syntheses are as follows: F2C¼S by a three-stepprocedure via dimerized thiophosgene which is fluorinated using SbF3 and the resulting 2,2,4,4-tetrafluoro-1,3-dithietane decomposed by pyrolysis <1965JOC1375> (Scheme 2).
Table 1 Thiocarbonyl halides—properties and references for the most useful syntheses
Compound Properties References
F2C¼S Colorless gas, b.p.�54 �C <1965JOC1375>Cl2C¼S Red liquid, b.p. 73.5 �C <1974S26>Br2C¼S Orange-red liquid, b.p. 142–144 �C <1974IC1778>I2C¼S Not yet isolated; identification by IR,
�C¼S=1062 cm�1 and �C�I=602 cm�1<1968ZAAC180>
FClC¼S Yellow liquid, b.p. 7 �C <1959ZOB3792>FBrC¼S Yellow liquid, b.p. 4–8 �C (100mmHg) <1981CB829>ClBrC¼S Red liquid, b.p. 47 �C (80mmHg) <1981CB829>
Cl3C SCl
Cl3C SCl CCl
SCl
CCl
SCl
Reduction
H2S, 114 °C
Reduction
(SO2, KI, S2Cl2)
96%
97%
Scheme 1
496 Functions Containing a Thiocarbonyl Group and at Least One Halogen
Br2C¼S from F2C¼S in 97% yield by reaction with anhydrous HBr <1974IC1778> andI2C¼S from carbon monosulfide by reaction with I2 <1968ZAAC180>.
The three thiocarbonyl halides with dissimilar halogens reported thus far have been obtained asfollows: FClC¼S from FCl2CSCl in 87% yield by reduction using Sn/HClconc <1959ZOB3792>;FBrC¼S from FClC¼S by halogen exchange using BBr3 at 65
�C <1981CB829> and ClBrC¼Sfrom thiophosgene by halogen exchange using BBr3 <1981CB829>.
The high-temperature thiation of thiophosgene with elemental sulfur has been reinvestigated byChristensen and Senning <2000SUL23>. The reaction was shown to lead to a multitude ofprimary, secondary, and tertiary products which are probably the result of the cycloaddition ofthiophosgene S-sulfide Cl2C¼S¼S and/or thiophosgene S-disulfide Cl2C¼S¼S¼S followedby sulfur extrusion and various dechlorination/chlorination steps.
6.17.1.2 Sulfoxides of Thiocarbonyl Halides (Sulfines)
Four sulfoxides of thiocarbonyl halides are known thus far and all were synthesized prior to 1995(see Table 2 for characteristic properties and the most useful syntheses). They are very labilecompounds and can be detected only under extreme conditions except for thiophosgene-S-oxide(dichlorosulfine). The synthesis, structural analysis, and chemistry of dichlorosulfine have beenreviewed <1992SUL275>. In its simplest preparation, it is obtained from 2,2,4,4-tetrachloro-1,3-dithietane by oxidation using trifluoroperoxyacetic acid at 40 �C and the resulting 1,3-dioxidequantitatively cleaved by vacuum pyrolysis at 480 �C and 0.5mmHg <1983CB1623> (Scheme 3).
Dichlorosulfine can also be obtained from thiophosgene directly (by oxidation using peroxy-benzoic acid <1969TL4461>), from Cl3CSCl (by hydrolysis <1969CC878>) and from allyltrichloromethyl sulfoxide Cl3CSOCH2CH¼CH2 (by pyrolysis at 300–400 �C <1986CB269>). It ismuch more difficult to synthesize than the other three sulfoxides reported thus far (all wereobtained prior to 1995), since they decompose spontaneously at low temperatures. None havebeen isolated, but some have been identified on the basis of IR and MS analyses (cf. COFGT(1995)).
Cl
SCl
S Cl
Cl
Cl
SCl
S Cl
Cl
O
O
∆C
Cl
ClSO
CF3CO3H, CH2Cl2
40 °C 51%
Scheme 3
Cl
SCl
S Cl
Cl F
SF
S
F
F
SbF3C
Cl
ClC
F
F2 S 2 S
(475 –500 °C)
90%
Scheme 2
Table 2 Sulfoxides of thiocarbonyl halides—properties and references for the most useful syntheses
Compound Properties References
F2C¼SO Decomposes at �100 �C; detected by MS <1988JFC329>Cl2C¼SO Yellow liquid, b.p. 34–36 �C (25mmHg) <1992SUL275>Br2C¼SO Reddish liquid; identified by IR in an argon matrix <1985CB1415>FClC¼SO Decomposes at �100 �C; detected by MS <1988JFC329>
Functions Containing a Thiocarbonyl Group and at Least One Halogen 497
6.17.1.3 Thiocarbonyl Halides Containing One Halogen and One Other Heteroatom
6.17.1.3.1 Halogenothioformates, ROC(Hal)¼S
The syntheses of both fluoro- and chlorothioformates have been reported. Thiocarbonyl chloridefluoride (ClFC¼S) reacts readily with alcohols in the absence of solvent leading selectively to thealkyl fluorothioformates ROC(F)¼S (R=alkyl) <1959ZOB3792>. In particular, the arylchlorothioformates (PhOC(Cl)¼S) have been employed extensively as starting reagents for thesyntheses of the corresponding di- and trithiocarbonates and thiocarbamates (vide infra). Thesyntheses of bromo- and iodothioformates have not been reported as of early 2004.
6.17.1.3.2 Chlorothioformates, ROC(Cl)¼S
Phenols and its analogs react readily with thiophosgene in (chloro)hydrocarbon solvents togetherwith base to provide the corresponding aryl chlorothioformates in excellent yields, e.g.,<1985SUL61> (Equation (1)).
O
Cl Cl
Cl
Cl Cl
ClS
Cl Cl
OH
ClCl
Cl CCl
ClS
NaOH+
–HCl
Colorless solid; m.p. 108–112 °C
99%ð1Þ
Phenyl chlorothioformate PhOC(Cl)¼S, a yellow liquid boiling at 91 �C (10mmHg), can besynthesized easily employing this procedure with yields in excess of 95% (cf. COFGT (1995),<1983HOU(E4)408>). This compound has often been used for the syntheses of the correspond-ing di- and trithiocarbonates and thiocarbamates (vide infra) and has proven to be very useful forintroducing the thiocarbonyl functionality into organic compounds (vide infra). The in situpreparation of thiophosgene for the generation of phenyl chlorothioformate has been accom-plished by the chlorination of CS2, by the reduction of CCl3CSCl, or by the reduction of CCl3SHusing SO2 (COFGT (1995)).
The corresponding alkyl chlorothioformates (e.g., ethyl chlorothioformate, a yellow liquid, b.p.53–55 �C (40mmHg)) can be synthesized by three different approaches. (i) From thiophosgene, by thereaction with potassium alkoxide in the corresponding alcohol at low temperatures; yields are in excessof 90%, cf. Table 3<1986S760>. (ii) From thiophosgene, by the reaction with alkoxytrimethylsilanes;although not requiring basic conditions, the yields, however, are less than 35% <1986S760>. (iii) Bythe chlorination of bis(alkoxythiocarbonyl)disulfides with Cl2 or SOCl2 <1983JOC4750>. However,the yields are low, under 70%, and the reaction products are difficult to purify. In addition, it isstrongly advised that only very pure reagents be used for the preparation <1986S760> (Scheme 4).
In the development of non-nucleoside reverse transcriptase inhibitors and as part of a totalsynthesis of such, Hahn and co-workers <2000MI66> synthesized i-propyl chlorothioformate(i-PrOC(Cl)¼S) from i-propanol and thiophosgene (in DMF/Et3N). The i-propyl chlorothioformate
Table 3 Chlorothioformates—properties and yields <1986S760>
Compound Yield (%) Properties
EtOC(Cl)¼S 81 b.p. 46 �C (33mmHg); nD18 1.4879, �C¼S 1270 cm�1
n-BuOC(Cl)¼S 85 b.p. 62 �C (12mmHg); nD18 1.4815, �C¼S 1260 cm�1;
spectroscopic data provideda
n-PrOC(Cl)¼S 91 b.p. 42 �C (12mmHg); nD18 1.4885, �C¼S 1260 cm�1
i-PrOC(Cl)¼S 88b b.p. 34 �C (10mmHg); �C¼S 1280 cm�1
i-BuOC(Cl)¼S 89 b.p. 54 �C (10mmHg); nD18 1.4776, �C¼S 1278 cm�1
a <1984ZAAC136>. b In THF.
498 Functions Containing a Thiocarbonyl Group and at Least One Halogen
was not isolated but treated with a number of substituted anilines to provide the correspondingthiocarbamates (i-PrOC(S)NHAryl) in low yield <2000MI66>.
6.17.1.3.3 Halogenodithioformates, RSC(Hal)¼S
A number of halogenodithioformates RSC(Hal)¼S have been prepared, and are presented togetherwith their most useful syntheses in Table 4. The most effective route for the synthesis of F3CC(F)¼Sis by the reaction of FClC¼S withHg(SCF3)2 at room temperature<1972CB820> (yield,�96%). Ina similar fashion, C6F5SC(Cl)¼S was obtained from Hg(SC6F5)2 and thiophosgene <1984T4963>and F3CSeC(F)¼S from Hg(SeCF3)2 and FClC¼S at �78 �C <1976ZAAC114>. A few halogen-odithioformates have also been obtained by the reaction between thiols (RSH) and the correspondingthiocarbonyldihalogenides (Hal2C¼S) (COFGT (1995)): AlkSC(F)¼S in the absence of solvent<1959ZOB3792>; AlkSC(Cl)¼S in dry CS2 at room temperature in 55–70% yield<1984ZAAC136>; and AlkSC(Br)¼S in ether at room temperature under argon <1984ZAAC61>.
CCl
ClS C
Cl
AlkOS
CCl
ClS C
Cl
AlkOS
CAlkOS
SC OAlk
S
SC
Cl
AlkOS
SiMe3
(i) AlkOK +AlkOH
–65 °C
(ii) + 80 °C
(iii) Cl2 or SOCl2
AlkO
Scheme 4
Table 4 Halogenodithioformates—properties and references for the most useful syntheses
Compound Properties References
CF3SC(F)¼S Yellow liquid, b.p. 43 �C <1972CB820>CF3SC(Cl)¼S Orange oil, b.p. 98–100 �C (14mmHg) <1984JOC3854>CCl3SC(Cl)¼S Orange oil, b.p. 78–80 �C (0.04mmHg) <1986ACS(B)609>C2Cl5SC(Cl)¼S Orange oil, b.p. 108–109 �C (0.03mmHg) <1986ACS(B)609>EtSC(Br)¼S Deep red liquid, storage at �20 �C under argon
required; spectroscopic data provided<1984ZAAC61>
n-PrSC(Br)¼S Deep red liquid, storage at �20 �C under argonrequired; spectroscopic data provided
<1984ZAAC61>
n-PrSC(Cl)¼S Yellow liquid, b.p. 57 �C (21mmHg);nDrt 1.5795, spectroscopic data provided
<1984ZAAC136>
i-PrSC(Cl)¼S Yellow liquid, b.p. 83–85 �C (21mmHg);nDrt 1.5699, spectroscopic data provided
<1984ZAAC136>
n-BuSC(Cl)¼S Yellow liquid, b.p. 103–104 �C (21 mmHg);nDrt 1.5696, spectroscopic data provided
<1984ZAAC136>
CF3SC(Br)¼S Red liquid, b.p. 57–58 �C; spectroscopic data provided <1976CB3432>CF3SeC(F)¼S b.p. 57–58 �C; spectroscopic data provided <1976ZAAC114>CF3SeC(Cl)¼S Yellow viscous oil <1976ZAAC114>CF3SeC(Br)¼S Liquid, b.p. 54 �C (50mmHg);
spectroscopic data provided<1986ZN(B)413>
EtSeC(Cl)¼S Red, viscous oil, b.p. 88 �C (23mmHg);spectroscopic data provided
<1984ZAAC61>
i-PrSeC(Cl)¼S Red, viscous oil, b.p. 102–104 �C (23mmHg);spectroscopic data provided
<1984ZAAC61>
CF3SeC(Cl)¼SO Yellow liquid, b.p. 47 �C (10mmHg) <1986ZN(B)413>CF3SeC(Br)¼SO Yellow liquid, b.p. 60 �C (10mmHg) <1986ZN(B)413>
Functions Containing a Thiocarbonyl Group and at Least One Halogen 499
The analogous selenoesters (AlkSeC(Cl)¼S) have also been produced from the reaction ofalkyl selenols <1976ZAAC114>. In addition, F3CSeC(Cl)¼S has been synthesized fromF3CSeC(F)¼S in 97% yield by halogen exchange using BCl3 <1976ZAAC114> andF3CSeC(Br)¼S from F3CSeC(F)¼S after UV irradiation for 4 h and halogen exchange withBBr3 at 40 �C in 74% yield <1986ZN(B)413>. The sulfines were produced by oxidation of thehalogenodithioformates using m-chloroperoxybenzoic acid (MCPBA) <1986ZN(B)413>.
6.17.1.3.4 Chlorodithioformates, RSC(Cl)¼S
There are five main routes available for the synthesis of the chlorodithioformates.
(i) From thiols
For example, alkyl chlorodithioformates (cf. Table 4) can be easily synthesized from the corre-sponding alkyl thiols and thiophosgene in good yields at room temperature <1984ZAAC136>,and similarly from the aryl thiols <1985SUL61>.
(ii) By the insertion of carbon monosulfide
This method has been employed for the syntheses of a number of alkyl and aryl chlorodithio-formates <1984JOC3854, 1984JA263, 1986SUL203, 1986ACS(B)609, 1991SUL143,1998SUL53>. (It should be noted that the continuous production of CS requires special careand equipment <1986ACS(B)609>.)
(iii) From sulfochlorides
For example, methyl chlorodithioformate MeSC(Cl)¼S can be obtained from (MeS)2CClSCl byhydrolysis (using water, aqueous KI, or MeSH), from MeSC(Cl)2SSMe (again by hydrolysis usingwater, aqueous KI, or MeSH), or from MeSC(Cl)2SCl (using MeSH) <1992SUL275>.
(iv) From alkali metal dichlorodithioformates
Alkali metal dichlorodithioformates MSC(Cl)¼S, prepared from alkali chlorides/NaOH and CS2<1983ZAAC7>, have been alkylated, for example, using ethyl iodide to yield ethyl chlorodithio-formate EtOC(Cl)¼S <1983ZAAC7>.
(v) From arenediazonium salts and CS2
Aryl chlorodithioformates have been produced by the reaction of arene diazonium chlorides withCS2 under Sandmeyer conditions (Cupowder or CuCl at room temperature) (Scheme 5).
N N ClCS2
X
SC S
Cl
X
SH
X
CCl
ClS S
C SCl
X
(i)CuCl
+NaOH, CHCl3
–HCl(ii)
–+
Scheme 5
500 Functions Containing a Thiocarbonyl Group and at Least One Halogen
6.17.1.3.5 Thiocarbamoyl halides, R2NC(Hal)¼S
In addition to a number of thiocarbamoyl chlorides (R2NC(Cl)¼S), some fluoride <1970LA195,1970LA158, 1975LA1025> and bromide analogs <1970LA195, 1972LA145> have also beensynthesized. Only the N,N-disubstituted derivatives of thiocarbamoyl halides are sufficientlystable to enable isolation; the N-monosubstituted thiocarbamoyl halides decompose sponta-neously after formation to the corresponding isothiocyanates with the evolution of HCl.
Fluorothiocarbamates have been obtained directly from the reaction between thiocarbonylchloride fluoride and secondary amines. A few other patented methods have been reported,e.g., N,N-dimethylthiocarbamoyl fluoride was obtained by treating F2C¼CFR (R=H, Cl,CF3) with tetramethylthiouramide sulfide at 130–135 �C (COFGT (1995)).
The thiocarbamoyl bromides R2NC(Br)¼S known thus far have been produced by the reac-tion between bromine and the thiocarbamoyl chlorides R2NC(Cl)¼S.
6.17.1.3.6 Thiocarbamoyl chlorides, R2NC(Cl)¼S
Thiocarbamoyl chlorides are sufficiently stable to permit isolation; selected examples are listed inTable 5. Dimethyl and diethylthiocarbamoyl chloride and other N,N-disubstituted analogs con-tinue to be very popular as reagents for introducing sulfur into organic compounds.Dimethylthiocarbamoyl chloride has been investigated using gas-phase electron diffraction<2003JPC(A)4697>; the molecule exists as a single near-planar conformer in the gas phase.
There are three main synthetic routes.
(i) From thiophosgene and secondary amines or their synthetic equivalents
Thiophosgene reacts readily with secondary amines in inert solvents to yield thiocarbamoylchlorides. The HCl formed in the reaction can be taken up by a further equivalent of thesecondary amine without formation of the corresponding thiourea derivatives <1970LA158,1975LA1025> (cf. Table 5).
Alternatively, thiophosgene can be reacted with N-trimethylsilylimide, triphenylphosphiniumchloride, or N-trimethylsilyl-1,3-dimethyl-2-imidazoline <1987UKZ395> to effect the same result<1997ZN(B)1055> (Scheme 6).
If trialkyl-substituted hydrazines are used instead of secondary amines, the correspondingthiocarbazic acid chlorides (R2NN(R)C(Cl)¼S) result (cf. Table 5) <1972CB2854,1991AP(324)917>. Thiocarbazic acid chlorides are very useful reagents for the thiocarbazoylationof thiazine-2-ones and thiazolidin-2-ones <1991LA405> (Equation (2)).
Table 5 Thiocarbamoyl chlorides—properties and references for the most useful syntheses
Compound Properties; method; yield References
Me2NC(Cl)¼S m.p. 43 �C; chlorination using SO2Cl2; 97% <1990SC2769>Et2NC(Cl)¼S b.p. 100 �C (21mmHg); Me2NH, S¼CCl2; 46% <1983HOU(E4)408>Et2NC(Cl)¼S b.p. 70 �C (13mmHg); chlorination using SO2Cl2; 97% <1988ZOB1468>O(CH2CH2)2NC(Cl)¼S b.p. 96 �C (17mmHg); O(CH2CH2)2NH, S¼CCl2; 83% <1988ZOB1468>Ar,a MeNC(Cl)¼S m.p. 44–45 �C; chlorination using CSCl2; 45% <1970LA158>Ar,b MeNC(Cl)¼S m.p. 79–80 �C; chlorination using CSCl2; 80% <1970LA158>Ar,c MeNC(Cl)¼S m.p. 108–109 �C; chlorination using CSCl2; 80% <1970LA158>Me2NN(Me)C(Cl)¼S m.p. 64–65 �C; method (i); 69% <1972CB2854>Me2NN(R)C(Cl)¼Sd m.p. 30 �C; method (i); 29% <1991AP(324)917>R2NN(Me)C(Cl)¼Se m.p. 93 �C; method (i); 54% <1991AP(324)917>R2NN(Me)C(Cl)¼Sf m.p. 41–42 �C; method (i); 23% <1991AP(324)917>
a 2-i-Propyl-1,3,4-thiadiazolo-5-onyl. b 2-Phenyl-1,3,4-thiadiazolo-5-onyl. c 2-Cyclohexyl-1,3,4-thiadiazolo-5-onyl.d R=cyclohexyl. e NR2=morpholino. f NR2=piperidino.
Functions Containing a Thiocarbonyl Group and at Least One Halogen 501
R2N NHR CSCl
ClR2N NR C
Cl
SCH2Cl2
low temp.
R = Me
+
69%
ð2Þ
(ii) From tetraalkyl thiuramide disulfides
Thiocarbamoyl chlorides have also been synthesized by chlorination of the corresponding tetra-alkyl thiuramide disulfides. In addition to elemental chlorine, S2Cl2 has also been employed as achlorinating agent <1983JOC1449, 1988ZOB1468, 1990SC2769>. The yields are in excess of 70%in refluxing benzene or carbon tetrachloride (Equation (3)).
CR2NS S
C NR2
S S Cl2C
Cl
S
CCl4
R = Me
2R2N
80%ð3Þ
(iii) From thioformamides
The third method in general use is by the chlorination of thioformamides (obtainable from thecorresponding formamides by application of Lawesson’s reagent) using chlorine, SCl2, or SO2Cl2as the chlorinating agent. Both aliphatic and aromatic thiocarbamoyl chlorides can be obtainedemploying this method (Scheme 7).
6.17.2 FUNCTIONS CONTAINING AT LEAST ONE CHALCOGEN FUNCTION(AND NO HALOGEN)
6.17.2.1 Thionocarbonates (O,O-Diesters of Thiocarbonic Acid)
As thiocarbonylating agents for the esterification of alcohols and phenols, in addition to thio-phosgene, alkyl- as well as aryl chlorothionoformates and thiocarbonyldiimidazole have been
Ar NMe
CH OAr N
Me
CH S CCl4 NAr
Me
C SCl
Lawesson’sreagent SO2Cl2 /Et3N
Ar = Ph 78%
Scheme 7
Ph3P N SiMe3S CCl2
Ph3P N CCl
S
N
N
Me
Me
N SiMe3S CCl2 N
N
Me
Me
N CS
Cl
Ph3P NH2 ClS CCl2 Ph3P N C
Cl
S–+
Scheme 6
502 Functions Containing a Thiocarbonyl Group and at Least One Halogen
employed, the latter under especially mild reaction conditions. The yields obtained are generallygood. Table 6 lists the properties and starting materials for the syntheses of selected thionocar-bonates. The main synthetic routes are given as follows.
6.17.2.1.1 From thiophosgene
Both monohydroxy alcohols and cis-diols react readily with thiophosgene to form the corre-sponding O,O-diesters (cf., e.g., Scheme 8 <2002CAR397, 2000IJ241>).
This method especially (conditions: Cl2C¼S, CH2Cl2, dimethylaminopyridine, 0 �C to �10 �C)has been employed for the diastereoselective synthesis of the O,O-diesters of a number of diolswith complete retention of the configuration(s) present in the diols. Very often, the thionocarbo-nate group serves as an intermediate or protective group which can be easily converted into thecorresponding alkene by Corey–Winter elimination <1999HCA1610, 1997TA2967>.
Often, thionocarbonates (but also other derivatives of thiocarbonic acid) have been pro-duced as intermediates in the course of the deoxygenation of alcohols. For the deoxygenation
Table 6 O,O-Diesters of thiocarbonic acid—starting material and properties
O,O-Diesters of thiocarbonic acid
Starting material Properties Yield (%) References
OH
N
OH
BocPMB [�]D +43.7� 84 <2002JOC6896>(�) [�]20D �7.3�(+) [�]20
D+5�
6977
<1999TA3483>
SiOH
OHR=Boc, colorless oil;[�]20D +10.2�; NMR
71 <1997LA757>
HOCOOEt
HO
N
R
R=Bzl, colorless oil;[�]20D +37.2�; NMR
89
O OH
ClBr
OH
PvOPale yellow oil;[�]20D �6.7�
82 <1996H745>
O
OHHO
OMe
m.p. 106–108 �C 87 <1995JOC5170>
Functions Containing a Thiocarbonyl Group and at Least One Halogen 503
of C(2) of a protected L-arabinose, the secondary hydroxyl was reacted with several differentreagents to obtain various radical precursors, which were further treated under normal freeradical deoxygenation conditions to yield the deoxygenated product <2002CAR397>(Scheme 9).
The best yields were obtained for the S-methylxanthogenate, though the high flammability ofCS2 limits the use of this method to small-scale syntheses. The other reagents tested(PhN¼C¼S, C(S)Im2 and PhOC(S)Cl) did not yield promising results, either because theywere insuffficiently reactive or the reagents utilized were too expensive. The most efficientdeoxygenation was achieved by preparing the phenoxythiocarbonylester (R¼C(S)OPh) in situ(phenol/pyridine in anhydrous CH2Cl2 was treated with thiophosgene) which was then directlyreacted with the secondary alcohol <2002CAR397>.
6.17.2.1.2 From chlorothionoformates
Addition of phenyl chlorothionoformate [PhOC(S)Cl] to solutions of secondary alcohols (e.g., indry acetonitrile) led to the isolation of the corresponding thionocarbonates in good yields whichwere readily reduced to the dehydrogenation product. This method has widely been employed indifferent types of compounds (cf. Table 7). In a number of cases, the thionocarbonates were notisolated <2002JOC6896, 2001JOC8935, 2001BMCL1609, 1998JA13003, 1998AG(E)965,1998JOC44, 1995JOC7149, 1995LA1533> (Equation (4)).
OOH
O
O
Me
Me
BnO OOR
O
O
Me
Me
BnO O
O
O
Me
Me
BnOReagent
R = C(S)SMe, C(S)NHPh, C(S)Im2 , C(S)OPh
Scheme 9
OOH
O
O
Me
Me
BnOO
OO
O
Me
Me
BnOC
OPh
S
O
O
O
Me
Me
BnOCSCl2PhOH
CH2Cl2
CSCl2
CH2Cl2
OHHO OO
S
Pyr
–10 °C
DMPD
66–71%
Scheme 8
504 Functions Containing a Thiocarbonyl Group and at Least One Halogen
Table 7 Synthesis and properties of phenylthiocarbonates synthesized from the corresponding secondary alcohol
Compound Synthesis Properties; yield References
OR'RO
OMe
OR'O
OR'
OPhS
PhOC(S)Cl/pyridineCH2Cl2 �20 �C
Colorless foam,1H, 13C, IR, MS;94%
<2002CEJ1856>
O
NH
NO O
N CH N(CH3)2
OSi
OO O
O
SSiN,N-Dimethylaminopyridine/(DMAP)/acetonitrile/PhOC(S)Cl rt
Yellow foam,1H, 13C, MS;58%
<2000CEJ2409>
N
N
N
N
ODPC
N(i-Bu)2
ON
O O S
O
OSi
OSi
Pyridine/CH2Cl2DMAP/PhOC(S)Cl; rt
Light yellow foam,1H, 13C;
86%
<1999HCA1005>
Table 7 (continued)
Compound Synthesis Properties; yield References
SCO2Me
O OPh
S
Pyridine/THF/DMAP/PhOC(S)Cl; 0 �C
Red oil/E/Z isomers
TR, 1H, 13C, MS;
82%
<2000T3425>
O
O
O
OH O
OAc
HH
HH
OR
HH
HHO
OS
OR
Pyridine/DMAPacetonitrilePhOC(S)Clrt
1:1 mixture of diastereomers[�]D
29+25.5 �C (CHCl3)IR, 1H, 13C;66%
<1999JOC9416>
HO
RO
O
OPh
S
O
O R
O
ORRO
OPh
S
Acetonitrile (Ar)PhOC(S)Cl rt
Colorless foamUV, 1H, MS;62/82%
<1999JCS(P2)849>
OS
ORO
OH
H
H
H
OH
OR
ORO
H
H
H
HOR
OS
O Pyridine/CH2Cl20 �C PhOC(S)Cl/pyridine
Colorless viscous oil1H, 13C;75%
<1999EJO875>
O BaseO
O O
R
Si
O
SiS
O PhOC(S)ClDMAP/acetonitrile (Ar)
m.p. 73–80 �CIR, 1H77%
<1997JOC8309>
H
HO
R
O
C
OPh
SPhOC(S)Cl/pyridine/DMAP/CH2Cl2
Colorless oil1H, IR, MS85%
<1996T4257>
O
RO
RO
ON
NO
OH
CPhO
S PhOC(S)ClDMAP,acetonitrile
Colorless oil1H, MS;27%
<1996MI97>
NHN
OSi(i-Pr)2O
SiO(i-Pr)2
O
O
OCPhO
S
Pyridine (Ar)acetonitrileDMAP, 0 �C
Yellowish oil1H, 13C, MS (FAB)88%
<2000T1475>
CHR
OH
R'+ PhO C(S)Cl
CO
PhOS
CHR R'
RCH2R'ð4Þ
The HO�C(2) group of the ortho-ester of myo-inositol acts as an H-bond donor in abifurcated, intramolecular H-bond, and the HO�C(4) and HO�C(6) groups form a strongintramolecular H-bond with one of them acting as a donor and the other as an acceptor. Thisleads to markedly different nucleophilicities for the three HO groups; the C(4) hydroxy group canbe selectively monothiocarbonylated by 4-O-tolylthiochloroformate. The regioselectivity of thisacylation is evident from the lack of symmetry expressed in the 1H NMR spectrum of theresulting thionocarbonate <1998HCA688> (Equation (5)).
O
Bu
HO
OHO
CH3
C SO
OO O
Bu
O
OOH
OHH
CH3 O C(S)Cl+
ð5Þ
In the course of the �-deoxygenation of (�)-detoxinine, a (�)-hydroxylactam was converted tothe corresponding thionocarbonate in 85% yield, again employing phenyl chlorothionoformate,which also permitted a convenient determination of the enantiomeric purity (>99% ee by chiralHPLC) <1997JOC1668> (Equation (6)).
N
O
HO
Si OHi-Pr i-Pr
N
O
Si OHi-Pri-Pr
OC
OPhSC(S)Cl PhO
ð6Þ
Thionocarbonates have been successfully used in radical-initiated deoxygenation reactions incarbohydrate derivatives. Phenyl thiocarbonates are well suited because of the high reactivity ofPhOC(S)Cl with secondary alcohols and because the resulting thionocarbonates undergo cleanphotolytic cleavage. Photolysis yields the allylic product stereochemically pure (71–78%)<1995ACS217> (Scheme 10).
O B
OH
O
OSiO
i-Pr2Si
O B
O
O
OSiO
i -Pr2Si
CPhO
O
O BO
OSiO
i -Pr2Si
UV
CH CH2
i-Pr2
DMAPCH2Cl2, rt
i -Pr2
i -Pr2
Bn3Sn2CH2
PhO–C(S)Cl
Scheme 10
508 Functions Containing a Thiocarbonyl Group and at Least One Halogen
6.17.2.1.3 From thiocarbonyldiimidazole
Thiocarbonyldiimidazole reacts with alcohols and 1,2-diols forming acyclic or cyclic thiocarbo-nates, respectively (COFGT (1995)). Examples of the formation of a thionocarbonate (whichwas reduced with tributyltin hydride and AIBN in an ensuing step) from thiocarbonyldiimida-zole and a secondary alcohol <2000T4667> or a 1,2-diol <2002CL1879> are the following(Scheme 11).
The same procedure for the syntheses of various thionocarbonates has been employed for other1,2-diols <2002TL2801, 2002T2339, 2001T3567, 2001OL2141, 1999BMCL2625, 1999OM2061>.Additionally, cyclic thionocarbonates can be used for protecting glycols <1997JOC4159> andpossess similar properties as carbonates, i.e., they are stable in acidic media but are converted tothe starting diols in basic media by hydrolysis.
Phenyl 2,3-O-thionocarbonyl-1-thio-�-L-rhamnopyranosides (readily prepared from 2,3-diolsin the presence of thiocarbonyldiimidazole, yield 81%) by the action of methyltrifluorometha-nesulfonate (MeOTf) afforded the 3-O-(methylthio)carbonyl-2-S-phenyl-2,6-dideoxy-�-L-gluco-pyranosides (ready precursors of the corresponding 2-deoxy-�-glycosides) in high yields(Scheme 12).
More specialized methods for the syntheses of thionocarbonates have been reviewed elsewhere<1983HOU(E4)408> (COFGT (1995)).
H
S
NNN N
OHOH O O
R
S
NNN N
DMF OO O O
RS
H
N
CH3O OH
N
CH3OO
N
CH3O
N
CH3O
O OCH3
S
O
/DMF
Then MeOH 36%
95%
Scheme 11
OROHO
SPh
OH
S
NNN N
THF
OROO
MeSS
SPhORMeOTf
ROH
ORO
SPh
OO
S
Scheme 12
Functions Containing a Thiocarbonyl Group and at Least One Halogen 509
6.17.2.2 Dithiocarbonates (Esters of Dithiocarbonic Acid)
Dithiocarbonic acid [S¼C(OH)SH] cannot be isolated as it decomposes spontaneously. Themono-O-esters also decompose readily, especially in acidic media, but are sufficiently stable toenable isolation at low temperatures and to be analytically characterized. The salts (xanthates) arestable but the synthetic efforts within the review period mainly concentrated on the chemistry ofthe corresponding diesters <1983HOU(E4)408> (COFGT (1995)).
6.17.2.2.1 Salts of O-alkyl esters of dithiocarbonic acid (xanthates) andbisalkoxythiocarbonyl disulfides
Usually the sodium or potassium salts (e.g., ROC(S)S�K+) were synthesized. These xanthateswere prepared from the corresponding alcohols ROH, CS2, and KOH using the same alcohol assolvent if possible. Practically all alcohols, including starch and cellulose, react<1983HOU(E4)408> (COFGT (1995)) (Equation (7)).
ROH CS2 KOH CS
RO S KH2O+ ++
– +ð7Þ
The xanthates have been used as precursors for the synthesis of dithiocarbonic acid diesters,and for this purpose, within the review period, only the compounds with R=Et or i-Pr had beenemployed.
The synthesis, spectral characterization, and X-ray structures of methylmercury(II) xanthates(MeOC(S)SHgR, R=Me, Et, i-Pr or Bn) have been reported <2002ICA71>. These compoundstend to form supramolecular, self-assembled, tape-like arrays in the solid state, whereas thecompounds with R=Et or i-Pr form double chains, and the compound with R=Bn formsdimeric units that do not interact with one another.
Within the review period, bisalkoxythiocarbonyldisulfides [ROC(S)SSC(S)OR] have beenemployed as precursors for the synthesis of dithiocarbonic acid diesters which are readily avail-able by the oxidation of the alkali metal xanthates (Equation (8)).
CS
RO S KCS
RO SCS
S OR2 Oxidation
– +ð8Þ
As oxidizing agents, the halogens, hypochlorite, bromocyan, and K2S2O8 have been mostlyutilized, but other reagents have been employed as well. Yields were high and the bisalkoxythio-carbonyldisulfides are considered to be very useful, easy-to-handle reagents <1983HOU(E4)408>(COFGT (1995)).
EtOC(S)S�K+ in THF/H2O was used to synthesize the analogous bisethoxythiocarbonyl tri-and tetrasulfides (by the addition of SCl2 and ClSSCl, respectively), which are in use as newsulfur-transfer reagents for the sulfurization of the nucleoside linkage of oligonucleotides<1997USP14961> (Scheme 13).
CEtO SS
K CEtO SS
S S S C OEtS
CEtO SS
S S C OEtS
+SCl2CEtO SS
K
THF/H2O+ S2Cl2
THF/H2O
– +
– +
Scheme 13
510 Functions Containing a Thiocarbonyl Group and at Least One Halogen
6.17.2.2.2 O,S-Diesters of dithiocarbonic acid
O,S-Diesters of dithiocarbonic acid have proven to be an invaluable class of compounds whichplay an important role in free-radical chemistry, such as for the deoxygenation of alcohols, radicalcyclization, and isomerization <1983HOU(E4)408> (COFGT (1995)). These methodologies havefound wide application in the synthesis of natural products and their analogs by favoring theradical process and suppressing the side reactions.
(i) From alkali salts of O-esters of dithiocarbonic acid
For the preparation of the O,S-diesters of dithiocarbonic acid, mostly sodium or potassiumxanthates were simply alkylated using common organic solvents <1983HOU(E4)408>(COFGT (1995)); yields ranged from good to excellent.
The synthesis of S-vinyldithiocarbonates is not straightforward because nucleophilicsubstitution at the vinylcarbon is difficult. However, a general method for the preparation isnow available: the reaction of potassium dithiocarbonate with vinylphenyliodonium salt intetrahydrofuran (THF) occurs quickly and in high yield <1999JCR(S)432> (Equation (9)).
CRO SS
K CHICHR'THF
CH CHR' S C ORS
+rt
PhBF4– –+ + ð9Þ
The reaction is stereospecific and retention of configuration was observed <1999JCR(S)432>.Though the conversion of tosyl-activated, optically active cyanohydrins with potassium
ethoxide-dithiocarbonate as the S-nucleophile under SN2 reaction conditions in dimethylforma-mide (DMF) was complete after 1 h, it was observed that at least 20% recemization had occurred.Nevertheless, the yields were good (66–70%) (Equation (10)).
RR
CNH
MeSO2OEtO C(S)S K
S
CNH
C OEtS
DMF, 1 h rt
R = n-Pr 97/95% ee
R= i-Bu 95/92% ee
37% ee
72% ee
– +
ð10Þ
The nucleophilic displacement of the bromine atom in �-bromo-�-thiobutyrolactone bythe O-i-Pr-xanthic group has been achieved in 45 min (cf. Table 8, entry 1) <1999S577>.Using this procedure, a benzotriazolyl-O-ethylcarbonodithioate (cf. Table 8, entry 2) and aalkythioethynyl-O-ethylcarbonodithioate (cf. Table 8, entry 3) were synthesized. Thexanthates CH2¼CHCH2CH(SC(S)OEt)CO2Et (from CH2¼CHCH2CHBrCO2Et) andPhC(O)CH(SC(S)OEt)CH2CH¼CH2 (from PhC(O)CHClCH2CH¼CH2) were also producedin good yields <1998SL1435> in addition to 5-O-Et-xanthomethyltetrazoles from thecorresponding 5-chloromethyltetrazole <1998TL19>.
7-Cyclohepta-1,3,5-trienylethoxydithiocarbonate has been prepared in 95% yield by couplingtropylium tetrafluoroborate with potassium ethylxanthate in acetonitrile solution <1995MC133>(Equation (11)) (Table 9a).
Functions Containing a Thiocarbonyl Group and at Least One Halogen 511
S
H
OEtS
BF4 EtO C(S)S KAcetonitrile0 °C, 4 h
95%
–– ++
ð11Þ
Both 1H and 13C NMR spectra indicate the pseudoaxial positioning of the ethoxydithiocarbo-nate group (�1 structure) and the fast, reversible migration of the ethoxydithiocarbonate groupalong the perimeter of the cycloheptatriene ring that occurs through a series of [1,7]-sigmatropicshifts (�G# (298K)=17.4–17.9 kcalmol�1).
Table 8 Synthesis and properties of O,S-diesters of dithiocarbonic acid
Entry O,S-diester Synthesis; yield (%) Properties References
1
S O
S C(S)OEt
S O
Br
Acetone, rt, 45 min;
100%
EtOC(S)S K– +
Stable orange oilIR, 1H, 13C
<1999S577>
2
NN
N
S OEt
S
NN
N
CH2Cl
KAcetone, rt, 4 h;
99%
EtOC(S)S– +White crystalsm.p. 72 �C1H, 13C
<2000H301>
3
C CS S C(S) OEtEtS
RO C(S) K
DMSO
C CClEtSrt, 60%
– +
Viscous liquid,cherry colorIR, 1H
<2000PS81>
4
C SMeMe
MeC
OEt
S
(EtOC(S)S)2
C NMeMe
NC
Cyclohexane3–4 h, reflux; 87%
2 Yellowish oilIR, 1H, 13C
<1999TL277>
5N
NC CNN
(EtOC(S)S)2
CN
N
2
Toluene3–4 h, reflux; 87%
m.p. 41 �C1H, 13C
<1999TC277>
512 Functions Containing a Thiocarbonyl Group and at Least One Halogen
The reactions of isomeric tetrachlorocyanopyridines with potassium Et-O-dithiocarbonate havealso been studied: tetrachloro-2-cyanopyridine was converted successively into the 4-mono- andthen the 3,4-bisethylxanthates; with additional potassium Et-O-dithiocarbonate, the last deriva-tive undergoes intramolecular cyclization with formation of 1,3-dithiolo[4,5-c]pyridine<1997CHE1306>. For the other polychloromonocyanopyridines, substitution of the chlorineatoms by the ethylxanthate fragment was observed, sometimes accompanied by the loss of COSinstead of heterocyclization <1997CHE1306>.
New S-alkylxanthates have been synthesized via the S-alkoxycarbonyl xanthates <1999T3791>;the latter compounds were obtained from the corresponding alcohols by the dropwise addition of asolution of phosgene in toluene and the crude alkylchloroformates that formed (obtained in nearquantitative yield) treated with potassium O-ethylxanthate in acetone. Finally, upon exposure ofthese yellow-colored S-alkoxycarbonylxanthates to visible light in an inert solvent under reflux, asmooth rearrangement took place affording the S-alkylxanthates in good yields (see Table 9a)<1999T3791, 1996CC1631> (Scheme 14) (Table 9b).
When 5-hexenyloxycarbonylxanthate was irradiated under the same conditions, a cyclopentanederivative was isolated. S-alkoxycarbonylxanthates derived from various substituted 3-buten-1-olsbehaved similarly, affording the corresponding lactones in all cases <1999T3791>.
Table 9a Synthesis and properties of S-alkylcarbonyl xanthates
S-alkylcarbonyl xanthate Properties
C(O)EtO C(S)OEt Bright yellow oil
C(O)C16H33O C(S)OEt Bright yellow oil
C(O)O C(S)OEtBright yellow oil
C(O)O C(S)OEt Bright yellow oil
C(O)O C(S)OEt Bright yellow oil
C8H17
H
H
O
S
O
CEtO
SPale yellow solidm.p. 88–89.5 �C[�]D +9.7�,IR, 1H; yield 79%
O
H
HAcO
CO
S COEt
S Pale yellow solidm.p. 77.5–79.5 �C[�]D �31�, IR, 1H;yield 52%
OCC
S
S
EtO
Yellow solidm.p. 133–134 �C[�]D +38� IR, 1H;yield 48%
Source: <1999T3791>.
Functions Containing a Thiocarbonyl Group and at Least One Halogen 513
EtO C(S)S KOHR
OEtSOR
O SR
S OEt
S
O S OEt
O S S CS
OEt
O S OEt
R1 O S
R2 R3 O
S CSOEt
R1 R3
R2
O
i. COCl2
ii.
hν
hν
hν
Toluenereflux
Toluenereflux
Scheme 14
Table 9b Synthesis and properties of S-alkyl xanthates
S-alkyl xanthate Properties
C(S)EtS OEt Yellow oil
C(S)C16H33S OEt Yellow oil
C(S)S OEtColorless liquid, IR, 1H; yield 61%
C(S)S OEt Colorless liquid, IR, 1H; yield 59%
C(S)S OEt Colorless liquid, (2:1 (E)/(Z))IR,1H; yield 52%
HSC
S
EtO
White solid (4:1 mixture of epimers),3�-isomers: m.p. 103-106 �C,[�]D+30,IR, 1H; yield 71%
H
S CS
OEtWhite, crystalline solid,m.p. 185–186�
C,[�]D �26, IR, 1H; yield 83%
SCEtO
S Colorless oil,[�]D +57, IR, 1H; yield 92%
S COEt
SColorless oil, IR, 1H; yield 87%
Source: <1999T3791>.
514 Functions Containing a Thiocarbonyl Group and at Least One Halogen
Potassium O-furfuryl dithiocarbonates have been employed as reactive intermediates for asimple synthesis of furfuryl sulfides via extrusion of COS <1995JCS(P2)1155>.
(ii) From bisalkoxythiocarbonyl disulfides
For the preparation of carbohydrate-derived S-xanthates which are attractive due to theirimportance as precursors for osides or anomeric activators (i-PrOC(S)S)2 was used. Theintroduction of the S-xanthate group was regiospecific and led to reasonable yields with reactionat the primary and anomeric hydroxyls of the sugars <1999OL521> (Scheme 15).
A complete selectivity for the primary hydroxyl site was observed for diol substrates possessinga secondary hydroxyl function, though the reaction appeared to be quite sensitive to steric effects.The direct conversion of the anomeric hydroxyl into O-alkyl, S-glycosyl dithiocarbonates in highyield reveals the efficiency of the method <1999OL521>.
A number of sterically hindered tertiary S-alkyldithiocarbonates were synthesized by thedecomposition of tertiary diazoderivatives (which can easily be made from the correspondingketone hydrazones) in the presence of dithionosulfides in good yield (cf., e.g., entries 4 and 5 inTable 8) <1999TL277> (Equation (12)).
CR2R1
EN N C R2
R1
E
(ROC(S)S)2
∆C CR2
R1
E OR
S
, –N2
ð12Þ
Two malonate xanthate derivatives were synthesized directly by reaction of the enolates of thestarting materials with diethyldithiobis(thioformate) (Scheme 16).
This is a direct way of transforming carbanionic centers into proradical ones, resulting in the‘‘Umpolung’’ of active methylene compounds.
HO
HO i -PrOC(S)S
Bu3P, (i -PrOC(S)S)2i -PrOC(S)S
Toluene, 1 h
Bu3P, (i -PrOC(S)S)2
Toluene, 1 h
OsideOside
CarbohydrateCarbohydrate
Scheme 15
COOEt COOEt
SC
OEt
S
COOEt
COOEt
S
COOEtEtOOC
COEt
S
i. LDA, THF–78 °C
ii. (EtOC(S)S)20 °C
i. NaH, DMSObenzene
ii. (EtOC(S)S)2rt
58%
50%
Scheme 16
Functions Containing a Thiocarbonyl Group and at Least One Halogen 515
(iii) From carbon disulfide
The preparation ofO,S-dithiocarbonates directly from the alcohols by reaction with a base, CS2, anda haloalkane has been used widely (COFGT (1995)). In the typical reaction procedure, the alcoholateis produced with NaH in THF, and catalytic amounts of imidazole, CS2, and the halomethane arethen added sequentially. A number of applications of this procedure have been reported after 1995.
2,2-Dimethyl-1,3-dioxan-5-ols have been converted into the corresponding methoxydithio-carbonates in good yields in the course of highly diastereoselective and enantioselective syntheses(de � 98% and ee=92–98%) <1998EJO2839> (Equation (13)).
O O
R2 R1OH
O O
OR1R2SMe
S
i. NaHii. CS2
iii. MeI
R1, R2 = Me, Et, i -Pr, Bn, CH2OBn, CH2O(CH2)2TMS
82–93%
ð13Þ
Employing the same procedure, S-propargylxanthate (BnOC(S)SCH2C�CH) was synthesizedfrom benzyl alcohol using propargyl bromide as the alkylating agent <1998TL7301>.
A tricyclic sulfide withC2 symmetry was synthesized via a radical-mediated route from the xanthate(prepared in excellent yield of 90% from the corresponding dibenzylidene acetal) using tributyltinhydride in toluene and �,�-diazoisobutyronitrile as initiator <2001TL7091> (Scheme 17).
The 3-O-xanthyl-1,2-cyclopropylglucal derivative, synthesized similarly from the correspondingsecondary alcohol, was used for the formation of 1-C-methyl-2,3-unsaturated sugars via tri-n-butyltin hydride-mediated ring opening <2001CL103>.
Other O,S-dithiocarbonates have been synthesized using the NaH/CS2/MeI method<1993TL2733> as suitable precursors for radical group transfer azidation <2001JA4717>, foran intramolecular carbocyclization in the course of the total synthesis of (+)-eremantholide Aand (�)-verrucatol <2000MI3>, for the O,S-dithiocarbonates <2001TL859, 2001JOC1061>, forthe deoxygenation of primary <1998TL2483> and secondary alcohols in the course of the totalsyntheses of macrolide antibiotics <1998JA5921> and (R)-(�)-2,4-diphenylbutyric acid<2000JOC5371>, and for the synthesis of trifluoromethyl ethers by oxidative desulfurization–fluorination of the trifluoromethylated xanthates (cf. Table 10) <2000BCJ471, 1998BCJ1973>.
Allyl alcohols adsorbed on Al2O3�KF at room temperature reacted with CS2 and methyliodideto provide the S-allyl-S-methyl-dithiocarbonates (R1R2C¼CHCR3OC(S)SMe) <1995SC2311>.Yields were in excess of 50%, and the products, yellow liquids, were characterized by 1H and13C NMR and MS.
OO
O O
OH
OH
Ph
Ph
OO
O O
O
O
Ph
Ph
MeSS
SMeS
O
O
S
O
OPh Ph
OO
O
HO
OO
O
OCMeSS
OO
OMe
CS2
MeIrt
Toluene80 °C, 16 h
78%
CS2
MeIrt
Benzenereflux, 2 hα( )D 63°
67%87%
NaHTHF
Bu3SnHAIBN
NaHTHF
Bu3SnHAIBN
90%
Scheme 17
516 Functions Containing a Thiocarbonyl Group and at Least One Halogen
(iv) From CS2 and methyl iodide
1-(Methyldithiocarbonyl)imidazole, a yellow oil that has been characterized by 1HNMR, was producedby the reaction of imidazole with CS2 and methyl iodide in the presence of sodium hydride (vide supra).Xanthates result from the reaction of alcoholates (deprotonated using NaH in THF) directly with1-(methyldithiocarbonyl)imidazole at room temperature <1997SL1279> (Equation (14)).
NN Na
NN C
S
SMe R-OHCRO
S
SMe
i. CS2,THF, 0 °Cii. MeI Base
>95%98%
–+
ð14Þ
The conversion of alcohols to O-alkyl, S-methyl dithiocarbonates using 1-(methyldithiocarbonyl)-imidazole proceeds efficiently; primary, secondary, tertiary, benzylic, and aromatic alcoholsall reacted to provide products in high yields (>95%).
(v) By radical addition to alkenes
O,S-Diesters of dithiocarbonic acid added efficiently to unactivated alkenes by a radical mechan-ism to provide the corresponding adducts (Scheme 18).
When trifluoromethyl xanthates were employed, the trifluoromethyl group added to the leasthindered site of the alkene <2001OL1069>. The xanthate methodology is applicable for additionsto strained alkenes such as cyclobutenes, azetines, and cyclopropenes <2000TL9815>.
Table 10 Synthesis and properties of S-aryl and S-alkyl xanthates <2000BCJ471>
COSMe
SR
Compound Properties Yield (%)
4-Me–C6H4– Pale yellow oilIR, 1H, MS 82
4-Br–C6H4–CH2CH2– Pale yellow oilIR, 1H, 13C, MS 99
n-C16H33– Pale yellow oilIR, 1H, 13C, MS 88
OCS2Me
Pale yellow oilIR, 1H, 13C, MS
97
OCS2MePale yellow needlesm.p. 106–107 �CIR, 1H, MS
91
BrOCS2Me
Pale yellow oilIR, 1H, 13C, MS
99
SC
OR'R
S
R
R''
R
R''S
COR'
RS
R S
R''
CS
OR'
Initiator
Scheme 18
Functions Containing a Thiocarbonyl Group and at Least One Halogen 517
The intermolecular addition of the radical obtained from the xanthate to suitable allylic orhomoallylic amines proved to be the key step for the construction of various nitrogen heterocycles<1999TL3701>. By the same procedure, the electrophilic alkyl radicals served as useful precur-sors for annulation reactions and afforded cyclopentane derivatives in moderate-to-good yields<1998SL1435>.
Substituted S-phenacyl xanthates add intermolecularly to various alkenes <1997TL1759> andsterically hindered xanthates, and by the same process, add to allyl acetates and allyltrimethyl silane<1999TL277> and to allyl- and vinylboronates <2001CC2618> to provide the expected products.
The synthesis of benztriazole xanthates has been realized using a clean, efficient, and nontoxicxanthate radical process <2001H301> (Scheme 19).
The addition of the benzotriazol-1-yl methyl radical was observed to be regiospecific with thebenztriazol-1-yl methyl moiety adding to the unsubstituted side of an alkene double bond. The existenceof the radical could not be proven by ESR spectroscopy, but by-products which could only originatefrom the formation of the benzotriazol-1-yl methyl radical strongly implied the existence of such.
(vi) By other methods
A novel and convenient preparation for steroidal 1,3-oxathiolane-2-thiones (cis cyclic dithiocar-bonates) at room temperature in high yields has been reported by the reaction of steroidal 5�,6�-epoxides with CS2 in THF using lithium bromide as catalyst <1997TL5705> (Equation (15)).
C8H17
RO
O S
S
R
CS2, LiBr
R = H, OAc, Cl
THF, rt70–83%
ð15Þ
The cis products were obtained selectively as the sole products. The reactions of various oxiraneswith CS2 under the same reaction conditions have also been examined <1995JOC473>. The desireddithiocarbonates were obtained regioselectively in high yields, and the formation of the regioiso-meric trithiocarbonates and episulfides was suppressed (Equation (16)).
O
R
CS2 SO
S
R
OS
S
R
SS
S
R
S
RCat. ,,
ð16Þ
The selectivity and yield of the reactions were strongly reduced when other alkali halides wereapplied as catalysts <1995JOC473>. Using this method, 4-arylspiro[1,3-oxathiophene-2-thione]-5-tetral-1-one was prepared <2001MI365>.
NN
N
CH2 Cl
NN
N
CH2S OEt
S
NN
N
CH2
NN
N
CH2CHS
CEtO
S
CH2R
K
R
EtOC(S)SAcetone20 °C, 4 h
hνPeroxideor
– +
Scheme 19
518 Functions Containing a Thiocarbonyl Group and at Least One Halogen
A facile, one-pot synthesis of a number of insecticidal thiophosphoryl xanthates was performedusing the mild base 1,8-diaza[5,4,0]bicycloundeca-7-ene in the DBU-catalyzed sequential reactionof various alcohols ROH (R=allyl, i-Bu, n-Bu, s-Bu, 2-Ph-ethyl, furfuryl; all in excess) with CS2and diethoxyphosphoryl chloride <2001SL625> (Equation (17)).
R OH R OC
SH
SClP(S)(OEt)2 R
O SP
OEt
S SOEtDBU, CS2
0 °C rt
65–88%
ð17Þ
The catalyst in this reaction is mild and can be removed from the reaction mixture simply bywashing with water.
Another mild, chemoselective, and efficient protocol for the thiocarbonylation of alcohols andthe thiocarbamation of amines has been reported using CS2 and alkyl halides in the presence ofcaesium carbonate and tetrabutylammonium iodide (TBAI) <2001TL2055> (Scheme 20).
For the syntheses of various arylseleno- and aryltellurothionoformates (PhOC(S)SeAr andPhOC(S)TeAr, respectively), commercially available phenyl chlorothionoformate was reactedwith (Me3Si)3SiSeAr and (Me3Si)3SiTeAr, respectively, and 4mol.% of tetrakis(triphenylphos-phine)palladium. Yields were excellent, 86–96% after chromatography, and the products wereidentified unequivocally by 125Te and 77Se NMR <1998JOC5713>.
6.17.2.2.3 Sulfoxides of O,S-diesters of dithiocarbonic acid (sulfines)
Xanthates have been oxidized usingMCPBA in CH2Cl2 at 0�C<1997JCS(P1)2019> (Equation (18)).
R1O SR2
S
R1O SR2
SO
R1O SR2
SO
CH2Cl2+
(E ) (Z )
MCPBAð18Þ
NMR analysis of the sulfines (performed rapidly after reaction) showed that the (E)-isomerwas predominantly obtained (R1= i-Pr, R2=Bn), revealing that oxygen transfer occurs to theopposite side of the SR2 group. However, for another sulfine (R1=2,6-di-t-Bu-phenyl, R2=Me),the same analysis yielded the reverse result with an (E):(Z) ratio of 8:92. This sulfine could be keptwithout change for months at ambient temperature in contrast to the preceding one whichtransformed into a mixture of thiocarbonate and dithioperoxycarbonate upon standing. Thesulfine structure was determined by X-ray analysis which provided a C¼S bond length of1.669 A and an S¼O bond length of 1.506 A. The plane of the sulfinyl group is perpendicularto the plane of the phenyl ring and the C(7)–(S(2) bond has an s-trans arrangement in contrast tothe s-cis conformations of esters, thioesters, and dithioesters <1997JCS(P1)2019>.
R OH R X
R X
RO S
R'S
R NH2 RN S
R'S
H
'
'
+CS2, CsCO3, TBAI
DMF, 0 °C to rt
+CS2, CsCO3, TBAI
DMF, 0 °C to rt
Scheme 20
Functions Containing a Thiocarbonyl Group and at Least One Halogen 519
6.17.2.3 Thiocarbamates (Esters of Thiocarbamic Acid)
The free thiocarbamic acids (H2NC(S)OH and its analogs) cannot be isolated because they decom-pose spontaneously to COS and the corresponding amine, but their salts have been prepared<1983HOU(E4)408> (COFGT (1995)).
6.17.2.3.1 From O-alkyl or O-aryl chloroformates and amines
By reacting the easily available thiocarbamic ester chlorides with primary and secondary amines,the thiocarbamic acid O-esters can be synthesized. Inert solvents, e.g., chloroform or THF, wereused, sometimes in the presence of a base for neutralizing the HCl produced. By this procedure,aryl thiocarbamates (for the further synthesis of caffeic acid) were readily obtained<2000JOC6237> (Scheme 21).
Similarly, by using pyridine as the base, isoxazol-5(2H)-ones were reacted with thiocarbamoylchloride (and with various other thiocarbonyl chlorides) to provide the N-thioacetylated derivativesin moderate-to-good yields and with the formation (5%) of the competing O-thioacetylated isomer<1998JCS(P2)3245>.
To overcome the side reactions of the chloroformates, tertiary aliphatic amines were deal-kylated <1998TL4387, 1999AJC841> (Scheme 22).
Instead of chloroformates, the corresponding bis(ethoxythiocarbonyl)sulfide was employed tosynthesize the thiocarbamates of glucosamines <1996JA3148> and the dithiasuccinoylaminoprotecting group for the solid-state synthesis of peptide nucleic acids <1999JOC7281>.
PhO CCl
S
PhO CCl
S
N OPh
S
H
R
NO
R1
R2
O
H
NO
R1
R2
O
C OPhS
NH2
RTHFrt
Scheme 21
PhO Cl
S+
CH2Cl2
PhO NR2
SRCl
(N2), 1 h+
R3 = Me3, Et2Bn, Me, morpholine, Me2cinnamyl, quinuclidine,
R3N
70–95%
tropine, bicuculline, Me2t-Bu
Scheme 22
520 Functions Containing a Thiocarbonyl Group and at Least One Halogen
6.17.2.3.2 From N,N-dialkylthiocarbamoylchlorides and alcohols or phenols
This reaction proved to be another general method to prepare the corresponding thiocarba-mates by the reaction of alcohols with N,N-dialkylthiocarbamoylchlorides <1983HOU(E4)408>(COFGT (1995)). Further examples of this method have been published after 1995.
The 1:2 mixture of diastereomeric meso- and rac-diols was converted into the correspondingdithiocarbamates in good yield with retention of the diastereomeric ratio; the pure meso-compound yielded only the meso-dithiocarbamate <2000T5413> (Equation (19)).
ROH
OHR
O
O
Me2N
S
CMe2N
S
CH, Me
i. NaH, THF
ii. Me2NC(S)Cl
R = C
77–89%
ð19Þ
A number of thiocarbamates of 5-O-benzyl-1-O-methylribofuranoside were synthesized by thereaction of the sodium salt with several thiocarbamoyl chlorides in THF. Yields were in excess of80% and the thiocarbamates were employed as glycosyl donors for the stereoselective synthesis of�-D-deoxyribonucleotides. The best result, �:�=4:96, was obtained for the diethylcarbamate<1996CL99>. In the above reaction, the �-side of the glycosyl donor, was efficiently blockedby the O-thiocarbamoyl group and the reaction proceeded under the remote stereocontrol of theO-thiocarbamoyl directing group <1996CL629, 1997CL389, 1998MI101> (Equation (20)).
OOMe
OH
BnO
OH
O
Bn
NR2
S
ON
i. NaH, THF, rt
ii. R2NC(S)Cl
NR2 = NEt, NMe2,
ð20Þ
Many more phenol derivatives have been reacted by this procedure <2002T2831, 2001JOC2104,1995LA2221, 1995SL155, 1996SC2461, 1996SL1054, 1997SC2487, 1998TA2819, 1998TL9639,1999CC2169> (cf. Table 11). In one case <1998TL4219>, the thiocarbamate of a cross-conjugatedcyclopentenone derivative was synthesized (Scheme 23).
6.17.2.3.3 From N,N 0-thiocarbonyl diimidazole and alcohols
The mild procedure of functionalizing alcohols by employing thiocarbonyl imidazolides as inter-mediates is a standard procedure these days for the dehydroxylation of secondary alcohols. Theyields are high, but only in a few cases the thiocarbonyl imidazolides were isolated <2002TA759,2000T5819, 2000MI559, 1998JA1747, 2000T7173> (cf. Table 12), otherwise they were usedfurther without purification <1998CC871, 1999TL6979, 1999AP435, 2000H637, 2000H1885,2001TL8625, 1995JA10889, 1995CC719, 1996CC1661, 1997SL387> (Scheme 24).
6.17.2.3.4 From thiophosgene and 1,2-amino alcohols
Cyclization of the 1,2-amino alcohols with thiophosgene and triethylamine in methylene chloridegave an oxazolidinethione in 95% yield as a viscous oil which crystallized after several weeks. Theoxazolidinethione was finally acetylated with n-BuLi and n-PrCl in THF at –78 �C to provide thepropionyloxazolidinethione in 90% yield <2001JOC894> (Scheme 25).
By the same synthetic procedure, (�)-(hydroxyoxindol-3-yl)methylammonium chloride wastreated with thiophosgene to provide the desired product with a spiro ring system in 92% yieldas colorless crystals which were characterized by IR, 1H, and 13C NMR, UV, and MS<2001JOC3940>. Alkylation using methyl iodide, however, provided the S-alkylation product.
Functions Containing a Thiocarbonyl Group and at Least One Halogen 521
�-D-Mannopyranosylamine also reacted with thiophosgene under the conditions describedabove, whereby a cis-bicyclic thiocarbamate resulted. The corresponding trans-hydrindane-typeisomer, produced from the corresponding �-D-glucopyranosyl derivative, was not that stable dueto the strain resulting from the ring fusion <2001TL5413> (Scheme 26).
When oligosaccharides were reacted with thiophosgene, the bis[cyclic thiocarbamate]s were theonly products that could be isolated <1995CC57>.
6.17.2.3.5 From CS2 and 1,2-amino alcohols
This last reaction was also accomplished using CS2/triethylamine in THF; however, the yieldswere lower <2001JOC894> (Scheme 27).
Table 11 Thiocarbamates obtained from thiocarbamoyl chlorides
Compound Synthesis; yield Properties References
Me2N(S)CO
CC
CH
OC(S)NMe2
(a) NaH, THF, 20 �C(b) Me2NC(S)Cl, 20 �C; 98%
meso m.p. 134 �C, 1H, IRrac m.p. 89–90 �C,1H, IR
<2000T5413>
O OOMe2NC
S(a) NaH, DMF(b) Me2NC(S)Cl, 96%
m.p. 103–104 �CMS, 1H, 13C
<2002T2831>
CHO
O NMe2
S
(a) NaH, DMF(b) Me2NC(S)Cl, rt; 83%
Yellow solidm.p. 126 �CIR,1H, 13C, MS
<1995LA2221>
O NMe2
S
ArOH/acetonitrileMe2NC(S)Cl, KF(on alumina); 58%
Red, viscous liquid 1H <1996SC2461>
O NEt2
S
OMe
Et2N-C(S)Cl, DMAP,TEA, 1,4-dioxanereflux; 71%
Light tan crystalsm.p. 73–75 �C1H, MS
<1997SC2487>
O OC NMe2
S
CMe2NS
MeO OMe
DMF, NaH, Me2NC(S)Cl,85 �C; 80%
Colorless crystalsm.p. 132–195 �C1H
<1998TA2819>
Me
OHC OC(S)NMe2THF(N2), NaH,THF, Me2N-C(S)Cl,rt; 77%
m.p. 79–81 �C1H
<2000MI547>
522 Functions Containing a Thiocarbonyl Group and at Least One Halogen
The relative configurations of the vicinal hydroxy and amine substituents of �-hydroxyhistidinederivatives were determined by transformation into the corresponding oxazolidine-2-thiones usingCS2/TEA. The cis or trans configuration was easily determined by 1H NMR; for a cis stereo-isomer JH,H lies in the range 8–9.5 Hz, and for a trans arrangement JH,H lies in the range 5–8 Hz<1998JOC2731>.
Other 2-oxazolidinethiones have also been synthesized employing this synthetic procedure(cf. Table 13) <1995JOC6604, 1997H2471, 1999SC1627>.
The corresponding six-membered, 2-thiono-1,3-O,N-heterocycles were also produced by reac-tion of the corresponding amino alcohols with carbon disulfide in the presence of trimethylamineat room temperature <2001T3175> (Scheme 28).
The cis or trans configuration of the ring anellation of the two six-membered rings follows fromthe values of the J-couplings of H-8a (two 3Jax,ax couplings are observed in the case of the transisomer but only one in the case of the cis isomer).
The corresponding oxazolo[4,5-b]pyridine-2(3H)-thione was synthesized by the reaction of2-hydroxy-3-aminopyridine with potassium ethylxanthogenate <1997CHE1337>; the thionestructure of the compound was established by both 1H NMR and X-ray diffraction.
6.17.2.3.6 From isothiocyanates and alcohols
The addition of alcohols to isothiocyanates is useful as another general method for the prepara-tion of O-alkyl thiocarbamates. Some examples of the procedure that have been reported include<2002HAC280, 2001CAR123, 2001CPB361, 2001H279, 2000PS221, 1997CCC1491> (cf. Table14) (Equation (21)).
∆R N C SEtOH
R NH CS
OEtð21Þ
Triethylamine and sodium alcoholates were found to strongly accelerate the reaction. Phenolsonly add poorly to the phenyl isothiocyanates. The S-alkyl esters of N-alkyl(aryl) dithiocarbamicacid were converted into the corresponding O-alkyl(aryl)esters of N-alkyl(aryl)thiocarbamic acidusing alkali metal alkoxides in the presence of one or more alcohols as solvents<1997MIP5621132>.
In the presence of base, the formation of a six-membered cyclic thiocarbamate is slow, resultingfrom intramolecular nucleophilic addition of the C(5) hydroxyl group to the heterocummulenefunctionality of the furanose form, was observed <2000CAR218> (Equation (22)).
Ar OH R2N CS
Cl
Ar O CS
NR2
OEt
O
HO
O
+
OEt
O
O
O
Me2N
S
Me2N C(S) Cl
CH2Cl2
+ NaH, DMF, rt
DABCO0 °C
84%
–
–
Scheme 23
Functions Containing a Thiocarbonyl Group and at Least One Halogen 523
Table 12 Thiocarbonylmidazoyl derivatives obtained from the corresponding secondary alcohol
Compound Properties; yield References
NN
CO
POPh2
POPh2
S
cis: While solid, m.p. 192–193 �C,IR, 1H, 31P, MS;65%
trans: Brown solidm.p. 172–173 �CIR, 1H, 31P, MS
<2002TA759>
NN
CO
S
Me
TOS
NOMe
Pale yellow oil, 1H;84%
<2000T5819>
N
N
N
NO
O CS
N N
NH2
FO
OSi
O
SiWhite solidm.p. 135–137 �C,MS, 1H; 81%
<2000MJ559>
COOMe
R
H
O
O
OH
CNN
S
R = H
R = Me
Pale yellow solid,1H, 13C, IR, MS; 85%
White solid, 1H, 13C,
IR; 77%
<1998JA1753>
O
O
O
OTBS
S
N N
O
Colorless oil,IR, 1H, 13C, MS;82%
<2000T7173>
O CS
N N
OTBSColorless oil, IR, 1H,
13C, MS; 56%<2000T7173>
SBTO
OOTBS
O
S
N N
Yellow oil, IR, 1H,13C, MS; 89%
<2000T7173>
SBTO
OOTBS
O
S
N N
Yellow oil, IR, 1H,13C, MS; 73%
<2000T7173>
524 Functions Containing a Thiocarbonyl Group and at Least One Halogen
CH OHR1
R2
N
N
NN
CS CHR1
R2N
S
NO
CH2
R1
R2
+
Benzene, 80 °CNaHreflux
Scheme 24
HN O
S
n-Bu
N
NH3Cl
O
HO
H
N OMe
O S
n-Bu
OHNH2
n-Bu
S CCl2
EtCOCl
S CCl2
CH2Cl2 N
O
N
O
S
H
H
Et3NCH2Cl2
n-BuLiTHF
–+
Scheme 25
OOHOH
NH2HO
HOOO
OH
NHHOHO
S
O
OH
NH2HO
HOOH
O
OH
NHOHO
OS
H
HO O OOH
OH
OHOH
HO
HO
OH
O OOH
OH
HO
NO
SH
NO OH
H
S
S CCl2
Pyridine
Scheme 26
Functions Containing a Thiocarbonyl Group and at Least One Halogen 525
N
COOEt
NH2
HO
SO2PhN
ONH
COOEt
SO2Ph
S
N
COOEt
NH2
HO
SO2PhN
ONH
COOEt
SO2Ph
S
CS , Et3N2
CH2Cl2 rt
CS2 , Et3NCH2Cl2 rt
Scheme 27
Table 13 2-Oxazolidinethiones as synthesized from the corresponding �-amino alcohols
Compound Synthesis; yield Properties References
N
O
H
SHOH2C
CS2, H2O2,base; 100%
Colorless crystalsm.p. 57.5–59.5 �C1H
<1997H2471>
N
O
H
S CS2, KOH, Pb(NO3)2,H2O; 20%
White solidm.p. 94 �C1H, 13C
<1999SC1627>
N
O
H
S CS2, KOH, Pb(NO3)2,H2O; 14%
White crystalsm.p. 54 �C1H, 13C, MS
<1999SC1627>
N
O
H
S
PhH2C CS2, Et3N, NaOH; 63%Oil [�]D �93�
1H<1995JOC6604>
N
O
H
S
PhH2C
Me
Me CS2, Et3N, NaOH;60%
White solid m.p. 142–143 �C[�]D �187.3�1H, 13C
<1995JOC6604>
HO
HPhNH2 O
HPhNH
S
Ph
OHHNH2 NH
OS
Ph
HCHCl3 rt
CS2, Et3N
CS2, Et3N
CHCl3 rt
47%
43%
Scheme 28
526 Functions Containing a Thiocarbonyl Group and at Least One Halogen
O
OR
NRO
OR
C SDMF N
OO
H
OH
S HOH
D[α]
Et3N80 °C100%
–35.5°
ROO
ð22Þ
Isothiocyanates, under Evans conditions (Sn(Otf)2, N-ethylpiperidine) (COFGT (1995)),afforded the syn-aldol which was isolated as an intramolecularly derivatized heterocycle inmoderate chemical yield but with syn/anti selectivity <1995TL7081> (Equation (23)).
ON
O
N
O
BnCS
ON
OO
BnHN
O
S
FNO2
i. Sn(OTf )2
N-Et-piperidine
THFii. 4-F-3-NO2-benzaldehyde
ð23Þ
The photolysis of O-allyl- and O-but-3-enyl-N-phenylthiocarbamates in benzene readily pro-vided the corresponding S-allyl- and S-but-3-enyl-N-phenylthiocarbamates in good yields<1995JCS(P2)373>.
Table 14 O-Alkyl thiocarbamates synthesized from the corresponding isothiocyanates
Compound Synthesis; yield Properties References
NS
COOEt
NHEtOOC COEt
S EtOH (anh.) reflux;72%
Yellow crystalsm.p. 116–117 �CIR, 1H,13C,MS
<2002MAC280>
F
N
O
morph NC
OEt
S
H NaH/MeOH;0 �C;78%
Pale brown crystals
m.p. 103–104.5 �C[�]D �23.1�1H
<2001CAR123>
NH
OEt
S
CH3 CF3SO3–+
ROH reflux;85%
Red needlesm.p. 130–138 �CIR, 1H
<2001H279>
N
N
S
HNC
OOH
S
Ethyleneglycol reflux;69%
m.p. 205–207 �CIR, 1H
<2000PS221>
CHEtNH
OEt
CS
OMe
NaOMe, ether (N2);65%
m.p. 48–50 �CIR, 1H, 13C
<1997CCC1491>
Functions Containing a Thiocarbonyl Group and at Least One Halogen 527
6.17.2.3.7 N-acyl-1,3-oxazolidine-2-thiones as auxiliary agents
N-acyl-1,3-oxazolidine-2-thiones have been employed for auxiliary-based, highly diastereoselective aldoladditions. For the enolization, TiCl4/TMEDA <1997JA7883>, TiCl4/(�)-sparteine/N-methylpyrroli-dine <2002OL2253>, Sn(OTf)2/N-Et-piperidine in CH2Cl2 (�45 �C) <1998JCS(P1)9>, or Ti(Cl)4/DIPA in CH2Cl2 (78
�C)<2001TL5085> (followed by an aldehyde) have all been used (Equation (24)).
NO
PhPh
S O
NO
PhPh
S O
R
OH
NO
PhPh
S O
R
OH
+TiCl4/ sparteine
CH2Cl2, then RCHO
92:8 to 98:1
–
ð24Þ
Other 1,3-oxazolidine-2-thiones for the highly stereoselective construction of C�C bonds areknown (Scheme 29).
The camphor-based, chiral N-acetyloxazolidinethiones have been used as starting materials for:(i) a one-step enolate bromation–aldolizaton reaction to provide bromohydrins (with yields inexcess of 90%; additionally, the asymmetric induction of this reaction was shown to be excep-tionally high) <1999TL3577, 1999JOC6495, 1999TA3249, 2000JOC6752>; (ii) a racemization-free deacetylation of 3-acyl-1,3-thiazolidine-2-thiones <1999CC545>; and (iii) an asymmetricsynthesis of �-mercapto carboxylic acid derivatives <2001JA5602> (Equation (25)).
N
SC
O
MeR N
OH
Br
O
O
S
i. TiCl4, DIPEA
ii. Br2IPIPEAiii. RCHO
ð25Þ
6.17.2.3.8 By thermal conversion of 2-allyl thiobenzothiazoles
The thermal conversion of 2-allyl thiobenzthiazoles <2000CHE201> and O-methyl-S-allyl-N-acrid-inyl iminothiocarbonates <1998H505> to the corresponding thiones has been reported to occursuccessfully with yields greater than 60% (Scheme 30).
This S!N allylic rearrangement is the result of a concerted [3,3]-sigmatropic shift.
6.17.2.3.9 Other methods
The oxo groups in 6-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones could be replaced by sulfurby the fusion (melting) of the diones with tetraphosphorus decasulfide <2000EJM733>(Equation (26)).
NO
S
OR
NO
S
O
NO R
S O
R = Me, Et, Bu, Ph
R = Me, Et, i-Pr, Ph, Ph(X)
Scheme 29
528 Functions Containing a Thiocarbonyl Group and at Least One Halogen
N
O O
OCl
R
P4S10
N
O S
OCl
R
N
O S
SCl
R
+ð26Þ
The products were isolated in yields below 50% after column chromatography, and thestructures were confirmed by IR and 1H and 13C NMR.
Cyclic thionecarbamates were usually prepared by the reaction of amino alcohols with CS2 orthiophosgene (vide supra); treatment of 3-hydroxybutylisocyanide with sulfur in the presence of5 mol.% selenium and Et3N in refluxing THF for 3 h resulted in the formation of 1,3-oxazine-2-thione in 79% yield <1997PS335> (Equation (27)).
R NC
OH
HN O
S
RS (5 mol.% Se)
Et3NTHF, reflux
R = Me, Ph, CH2Cl
62–89%
ð27Þ
Oxazolidine 2-thiones were synthesized from alkenes by employing one-pot Co(II)-catalyzedepoxidation followed by cleavage with trimethylsilylisothiocyanate <1996TL7315> (Equation (28)).
Ph
Ph
N C S, Co(II) N
OS
Ph
Ph H
CHOi. Co(II), O2, (CH3)2CH
ii. Me 3Si
56%
–
–ð28Þ
The reaction is highly regio- and stereoselective as only one isomer was obtained and carefulanalysis of the reaction mixture indicated the total absence of the other regioisomer. The yields ofthe oxazolidine 2-thiones are improved considerably by using the epoxide instead of the alkene<1996TL7315>.
In an approach to artificial nucleoside synthesis, a sugar-derived 1,3-oxazolidine-2-thione wasproduced from free or partially-protected sugars in one step using potassium thiocyanate underacidic conditions <2001TL2977> (Equation (29)).
O O
N
OH
S
OH
H
SugarKSCN, HCl, H2O
80–100% ð29Þ
The structure of the sugar ring was clearly defined with formation of a furanose ring, confirmedby 1H and 13C NMR, and an anomeric configuration controlled by the hydroxyl located on C(2).
Novel, convenient syntheses of 1,3,4-oxadiazol-2-(thi)ones from N-t-Bu-diacylhydrazines havebeen reported by reaction with t-BuOK followed by treatment with thiophosgene <2001S1965>(Equation (30)).
∆
O
NS
O
NS
∆
S N Acr
OMe
R S N
OMeAcr R
Scheme 30
Functions Containing a Thiocarbonyl Group and at Least One Halogen 529
R NN R'
O
OH
But
O
NNR
R'O
S
i. t-BuOK / THFii. C(S)Cl 2
R, R' = alkyl, aryl
70–80% ð30Þ
6.17.2.4 Dithiocarbamates (Esters of Dithiocarbamic Acid)
The dithiocarbamic acids have been obtained from their alkali metal dithiocarbamates by treat-ment with HCl. However, they easily decompose in aqueous solution to produce CS2 and thecorresponding amines (COFGT (1995)). N,N-diphenyldithiocarbamic acid (m.p. 147 �C afterrecrystallization from benzene) and the N-acyldithiocarbamic acids (2-oxopyrrolidide, m.p.101–102 �C; and 2-oxopiperidide, m.p. 103–105 �C), however, are sufficiently stable to permitisolation <1983HOU(E4)408>.
Recently, ethoxydithiocarbamic acid [EtO2CNHC(S)SH] was isolated as pale yellow crystalsand unequivocally characterized by IR and 1H NMR. Upon standing in the air, it dimerizes toform [EtO2CNHCS2]2.
6.17.2.4.1 Alkali metal salts of N,N 0-disubstituted dithiocarbamic acid (dithiocarbamates)
Dithiocarbamates are usually prepared from CS2 and 2 equiv. of an amine using commonsolvents such as acetone or ethanol. When the reaction was performed in aqueous NaOH orKOH <1983HOU(E4)408> (COFGT (1995)), the corresponding sodium or potassium dithiocar-bamates were obtained (e.g., sodium 1,10-ferrocene-bis(dithiocarbamate) <1999SC1041> orpotassium 1,1-dioxothiolan-3-yl-dithiocarbamate <2000MI1014>); in ammonium hydroxidesolution, the ammonium dithiocarbamate was obtained <2001JIC372>.
The dithiocarbamate anions are good ligands for transition metals and a large number ofcomplexes have been constructed incorporating them. The sodium salts of the dithiocarbamateswere normally used, and the complexes obtained ([R2NC(S)S]TeMe2 <1997IC1890>,[R2NC(S)S]AsPh <1995PS13>, [MeC(S)NHC(S)S]M (M=K, Rb or Cs) <1995ZAAK439>,[R2NC(S)S]GeClPh2 <2002IJC(B)1510>, [RHNC(S)S]SnCy3 <2002MI13>) were characterizedby X-ray diffraction.
6.17.2.4.2 Esters of dithiocarbamic acids
(i) From carbon disulfide and base followed by alkylation
The synthesis of the esters of dithiocarbamic acid is conventionally separated into two steps: thefirst step is the synthesis of the dithiocarbamates by reaction of a secondary amine with CS2 in thepresence of a base; the second step is the alkylation of the dithiocarbamate salts, therebyconverting them to the corresponding S-esters (Equation (31)).
NHR1
R2CS2 N C
R1
R S
S
K
MeI
–KIN C
R1
R S
S
Me
KOH+ – +
ð31Þ
Following this procedure, the methyl esters of various dithiocarbamates were synthesized<2001L5621, 2000JFC181, 2000BMCL2779, 1998BCJ1973, 2001SL688>. By employingBrCH2CH(OEt)2 <1999SC3191, 1997S407> and several other alkyl halides <2001TL2055,1997M881> in the alkylation step, the corresponding S-esters were obtained.
Different kinds of dithiocarbamates have been prepared by a simple, one-pot procedure fromprimary or secondary amines, CS2, and a variety of alkyl halides in the presence of anhydrousK3PO4 under mild conditions in good yields <1998SC295>.
In a number of cases, the alkylation of the dithiocarbamates, e.g., with an �-halogenatedketone, was followed by cyclization to yield thiazole-2(3H)-thiones <2000JOC6069, 1998S1442>.
530 Functions Containing a Thiocarbonyl Group and at Least One Halogen
For the rapid synthesis of various thiadiazolylthiazol-2(3H)-thiones, a microwave-acceleratedsolid-state protocol has been described <2001SC817>. The preparation of the thiazolidinethionesfrom (1R,2S)-ephedrine or (1R*,2S*)-norephedrine was found to involve inversion of the config-uration, as determined by X-ray analysis <1995JOC6604>.
Employing different alkylating agents, further heterocycles containing the SC(S)N fragmenthave been synthesized: rhodamines with RCHBrCO2
� <1997CHIR568> and thiazole derivativeswith CH2ClCO2Et <2001MI269>.
When the reactionof aromatic primary amineswithCS2/Et3Nwas followedby treatmentwith aqueoushydrogen peroxide, the corresponding benzoxa(thia)zol-2-thiones were obtained<2000TL5833>.
(ii) From metal or ammonium dithiocarbamates
The S-alkylation, S-arylation, or S-acylation of alkali metal or ammonium dithiocarbamates byalkyl halides and related compounds is another general synthetic method for the preparation ofthe S-esters of the dithiocarbamates (Scheme 31).
New, substituted triazolyl dithiocarbanilates <1999MI15> and benzofuranyl dithiocarbamates<2001CHE1424, 1997PS411> have been synthesized using this methodology. N-hydroxy thia-zole-2-thione, loaded on a Wang resin, was treated along similar lines and was successfully usedas a supported reagent for a solid-phase version of the photochemical generation of radicals<2001OL855>.
A polymer-supported diethyldithiocarbamate anion reacted with primary and secondaryalcohols via their trifluoroacetates and produced alkylated dithiocarbamates in good yields<2000JCR(S)450>.
Treatment of a terpene alcohol with zinc N,N-dimethyldithiocarbamic acid in the presence oftriphenylphosphine and DEAD proceeded with inversion of the configuration at the carbon atomto provide the dithiocarbamate in 75% yield after chromatography <1999TA4129> (Equation (32)).
Me2N
S
S
R
HO
RPPh3
DEADZn(SC(S)NMe2)2
toluene
ð32Þ
Allyldithiocarbamates (Me2NC(S)SCH¼CHAr) have been produced by the reaction ofsodium dithiocarbamate with BrCH2Ph3P
+Br�. The intermediate, Me2NC(S)SCH2Ph3P+Br�,
in the presence of t-BuOK underwent a Wittig reaction with aldehydes to form the allyl dithio-carbamates in good yields <1996SC509>.
The aryliodonium salts proved to be very useful for the synthesis of S-aryl dithiocarbamates;nucleophilic attack of sodium dithiocarbamate afforded the sodium salt, after acidification of thecorresponding dithiocarbamate <1995CC325, 1995SC1627> (Equation (33)).
N
N
O
OO
IPhH
H
N
N
O
OO
SH
H
CS
NEt2i. Et2NC(S)SNa
DMF rtii. HCl
+
ð33Þ
Polymer-supported diaryliodonium salts have also been employed <2000JCR(S)352>.
CR2NS
SClCH2R' CR2N
SCH2R'
S
CR'Cl
OCR2N
S
S
C(O)R'
+
+
M
Scheme 31
Functions Containing a Thiocarbonyl Group and at Least One Halogen 531
Alkali metal dithiocarbamates also readily react with alkenes, exhibiting both electrophilic andnucleophilic properties, to form the corresponding S-alkylated reaction products <2000MI1245>(the same as they do with 1-naphthyldiazonium salts to provide the 1-naphthyl-azophenyldithiocarbamates <2001MI372>).
(iii) From isothiocyanates
The addition of thiols to isothiocyanates yielded the N-monosubstituted esters of dithiocarbamicacid. Triethylamine was found to accelerate the reaction.
Isothiocyanates and �-thiobutyrolactone, when gently heated with NaOH in a dioxane/watersystem and followed by acidification, yielded the 4-thiocarbamoylthiobutyric acids <1999JHC1167>,which can be easily cyclized to the seven-membered 2-thioxo-1,3-thiazepan-4-ones (Equation (34)).
S O
N
S
O
S
RN C SR
N CR
H S
S
OH
O+ i. NaOH
ii. HCl
ð34Þ
The nucleophilic addition of NaHS to hexa-2,4-dienoyl isothiocyanate afforded the cyclized6-(propen-1-yl)-2-thioxotetrahydro-4H-1,4-thiazin-4-one <1999MI260> (Equation (35)).
CO
NCS
NaSH
S
NH
O
S
i. MeOH
ii. Acetoneð35Þ
The corresponding benzothiazine-2-thione hetereocycle was prepared by intramolecular hetero-conjugate addition of isocyanates promoted by the CS2/TBAF system <2000TL4895>. Similarly,starting from isothiocyanates, �-D-(glucopyranosyl)-tetrahydro-2-thioxo-4H-1,3-thiazin-4-ones<1995LA2231> and thiazole-2-3H-thiones <1997PHA750> were prepared.
(iv) From thiuram disulfides
Anions of enolized heteroaromatic 1,3-dicarbonyl systems reacted with tetraalkylthiuram disul-fides, which in the reaction system DMF/K2CO3 were sufficiently electrophilic to produce theheterocyclic dithiocarbamates in good yields <1999M1147, 2000JHC911, 2000SUL287>. Treat-ment of the doubly lithiated 2-(pivaloylamino)pyridine with tetraisopropylthiuram disulfide gaverise to the 3-diisopropyldithiocarbamato derivative in high yield (Scheme 32).
The tetraethylthiuram disulfides also reacted under different reaction conditions with perfluor-oorgano silver(I) and perfluoroorgano cadmium compounds to provide the corresponding per-fluoroorgano esters of diethyldithiocarbamic acid and metal diethyldithiocarbamatesMSC(S)NEt2 (M=Ag or Cd/2), the latter product precipitating immediately in THF<2001ZAAC1264> (Equation (36)).
OH
O
OH
O
S CNR2
S
N NH CO t Bu N NH CO t-Bu
S CNi-Pr2
S
DMF/K2CO3
i. BuLiii. (i-Pr2NC(S)S)2
iii. HCl
(R2N-C(S)S)2
73%
Scheme 32
532 Functions Containing a Thiocarbonyl Group and at Least One Halogen
CEt2NS
SXRf THF CEt2N
S
SRfC NEt2
S
S
X2
+–30 °C
+
X = Ag, Cd/2
ð36Þ
(v) Other methods
Metal diethyl dithiocarbamates and their N-methyl quarternary salts have been shown to be efficientmethyldithiocarbonyl transfer reagents for the syntheses of dithiocarbamates <2000T629>(Scheme 33).
The yields for a number of aliphatic/aromatic primary and secondary amines were high, 70–85%(except for R= t-Bu), thus providing a facile route to methyldithiocarbamates from nonhazardousstarting materials.
The chemistry of both tri- and pentavalent compounds of As, Sb, and Bi from xanthate- anddithiocarbamate-based ligands has been reviewed <2003CCR35>.
Both arylalkylidene rhodanine <2000TL5729> and methyldithiocarbonyl transfer reagent foruse in solid-phase combinatorial synthesis (Equation (37)).
OC N N
S S
S
O
O
H
O N S
S
O
ð37Þ
(vi) N-acyl-1,3-thiazolidine-2-thiones as auxiliary agents
N-acyl-1,3-thiazolidine-2-thiones have been employed in auxiliary-based highly diastereoselectivealdol additions. For the enolization, TiCl4/(�)-sparteine <2000OL775> and TiCl4/N-ethylpyr-rolidine/CH2Cl2 <1996TL8949, 2000OL2151> followed by an aldehyde were employed. Diaster-eoselectivities greater than 90:10 were obtained (Equation (38)).
N S
O S
CHORR N S
OH O S
R N S
OH O S
TiCl4/amine +
>90:10
>50%
ð38Þ
The influence of several Lewis acids on the stereoselectivity and overall yield has been examined<2001TL4629>; the best diastereoselectivity was obtained when using SnCl4. The same highdiastereoselectivity was achieved for the Lewis acid-mediated cross-coupling reaction of dimethy-lacetals (up to 98:2) <2001OL615>.
N N C SMeS
CR2NSMe
S
N N C SMeS
Me
I
EtOH/∆
R2NH
Scheme 33
Functions Containing a Thiocarbonyl Group and at Least One Halogen 533
6.17.2.4.3 Bis-[thiocarbamoyl](thiuram)disulfides
Bis(thiocarbamoyl)disulfides were obtained by oxidation of the salts of dithiocarbamic acid (notalways isolated). A wide range of oxidation reagents have been used, from chlorine to ammoniumpersulfate <1983HOU(E4)408> (COFGT (1995)).
A new, attractive method under mild conditions has been reported for obtaining the tetraalk-ylthiuram disulfides (R=Me, Et, i-Pr, cyclohexyl, CH2CH2OH). Dialkyldithiocarbamic acid orthe sodium salt were subjected to sodium chlorite, and the tetraalkylthiuram disulfides wereobtained instantaneously, pure and in very high yields <1995SC227> (Equation (39)).
CR2NSH
SCR2N
S
S
SC NR2
SNaClO2/H2O
0–5 °C, 20 min
73–93%
ð39Þ
Tetrabutylthiuram disulfide and bis[(3-methoxycarbonyl-5-methyl-pyrazol)-1-yl thiocarbonyl]disulfide were prepared by dissolving the appropriate amine in ethanol, adding CS2 to the cooledsolution followed by the addition of solid iodine. Yields ranged from 83% to 90% <2001MI232,2001MI234>.
6.17.2.5 Trithiocarbonates (Esters of Trithiocarbonic Acid)
Trithiocarbonic acid has been isolated as a reddish liquid at room temperature (m.p. –26.9 �C) butis unstable and decomposes into CS2 and H2S. At �78 �C though, it can be stored for extendedperiods of time. The salts of trithiocarbonic acid are more stable and rather easily available. Withthe exclusion of moisture, they can be stored without decomposition <1983HOU(E4)408>.
6.17.2.5.1 Salts of monoesters of trithiocarbonic acid
The blood-red trithiocarbonate anion S¼CS22� has been prepared by treating ammonium
sulfide, strong aqueous ammonia, alkali metal sulfides, or aqueous alkali metal hydroxide withCS2 <1983HOU(E4)408, COFGT-II>. To promote the reaction, a phase-transfer catalyst or ananion-exchange resin has often been used <1998JCR(S)454>.
The reaction of aliphatic and aromatic thiolates with polarized CS2 leads to the formation ofthe salts of the monoesters of trithiocarbonic acids, e.g., the stable triethylbenzylammonium(TEBA) salts of the corresponding trithiocarbonic acid <1996JCR(S)64> (Equation (40)).
NN CH2 CN N
N CHCN
CS
SCS2
S
SS
TEBA ClCS2/OH
TEBA
–
–
–
+
+ TEBA+
TEBA+
ð40Þ
6.17.2.5.2 Diesters of trithiocarbonic acid
(i) From thiophosgene or xanthates
The diesters of trithiocarbonic acid have been produced from thiophosgene and thiols, thiophe-nols, or their salts. The dithiols <1997PS413, 2000PS153> and dithiolates as well as disilanylsul-fanyl derivatives <2001T5739> produced cyclic trithiocarbonic esters.
In the case of the disilanylsulfanyl derivatives, the reaction yields were shown to improve considerablyif phenyl chlorothionoformate PhOC(S)Cl was used instead of thiophosgene. The 1,3-dithiol-2-thionederivatives were also obtainable as cyclization products of the RSC(S)Oi-Pr derivatives, which weresynthesized from pyridyl acyl bromide and NaSC(S)Oi-Pr <2001TL1571> (Scheme 34).
534 Functions Containing a Thiocarbonyl Group and at Least One Halogen
(ii) From carbon disulfide
Symmetrical trithiocarbonates were obtained directly and in excellent yields by the reaction ofprimary or secondary alkyl, benzyl, or allyl halides with KOH and CS2 in anhydrous THF<1995JCR(S)478, 1996JCR(S)64> (Equations (41) and (42)).
2 RX
S
SSR RCS2, KOH, THF
X = Hal
60–90%ð41Þ
N
Me
Ph
CN
O
NC
HS N N
Me
Ph
CNNC
O
Me
Ph
CN
O
NC
SS
SCS2/ TEA, Pb(ac)2 ð42Þ
The corresponding bis(azinyl)trithiocarbonates were synthesized from the corresponding pyr-idone thiol using the same methodology but by using CS2 in the presence of triethylamine andPb(II)Ac2 <1995H2195>.
In the presence of an anion-exchange resin in the hydroxy form, primary, secondary, allylic, andbenzylic halides were converted, by the reactionwithCS2 undermild reaction conditions, exclusively intothe corresponding dialkyl trithiocarbonates. Theywere obtained as virtually pure products (according to1H NMR) in excellent yields (>90%) and in considerably shorter reaction times <1998JCR(S)454>.
The synthesis of the 1,3-dithiol-2-thione-4,5-dithiolate anion employing the carbon disulfideroute (CS2/Na/DMF) has been reviewed in 1995 <1995PS145>.
A convenient, one-pot preparation of 1,3-dithiol-2-thiones and 1,3-diselenol-2-selenones, sub-stituted with phenyl, alkyl, alkylthio, hydroxymethyl, or formyl groups, from readily availableacetylenes and CS2 has been reported in good-to-excellent yields <1997SL319> (Equation (43)).
C CHRX
XX
R
H
i. n-BuLi/ THFii. X
iii. CX2
X = S, Se; R = H, Ph, SMe, n-Hex, CH(OEt)2
>75%
ð43Þ
Tetramethylethylenediamine was usually found to be effective for enhancing the yields, espe-cially for the selenium compounds.
(iii) From the salts of trithiocarbonic acid or monoesters
Vinyl esters of trithiocarbonic acids have been stereoselectively prepared by the reaction ofpotassium S-alkyl(aryl) trithiocarbonates with vinyl(phenyl)iodonium tetrafluoroborate<2000SC3897> (Equation (44)).
N COCH2BrH2O
N CO CH2 S CS
Oi-Pr
P4S10N
S
SS
CN
S
SO
C
NaSC(S)Oi-Pr H2SO4, 50 °C
70 °C
70%
45%
Scheme 34
Functions Containing a Thiocarbonyl Group and at Least One Halogen 535
CRSSK
SR'CH CHI PhBF4
THFCH CH SR' SR
S
+rt
R = Et, PhCH2, Ph; R' = Ph, n-Bu
>60%
–+
ð44Þ
In the case of R1=Ph, retention of the configuration was observed. However, in the case ofR1= n-Bu, complete inversion of the configuration was obtained, the reaction probably proceed-ing via an SN2-type reaction mechanism.
(iv) From bisalkoxythiocarbonyl disulfides
The 1,3-dithiol-2-thione ring was also prepared in a one-pot reaction from bis(diisopropylox-ythiocarbonyl) disulfide and various alkynes under radical conditions, the five-membered hetero-cycle being formed via the ring closure of a vinyl radical <1998H2003> (Equation (45)).
R'R S
SR
R'
S(i-PrS-C(S)-S)2
R, R' = aryl, alkyl
AIBN
>40%ð45Þ
The reaction was optimal for alkynes conjugated with a C¼C double bond.
(v) Other methods
The reaction of stannylenes with an excess of CS2 resulted in the formation of a chrome-yellowasymmetric alkene, the structure of which was established by X-ray diffraction <1995OM3620>(Scheme 35).
The strain inherent in the thietene ring serves as the driving force for its expansion via breakageof the weak C�S bond under mild conditions. The ring expansion using CS2/THF was catalyzedby alkali metal halides and afforded the corresponding six-membered dithiocarbonates in highyields <2002IJC1234>. The products were obtained as racemates (Equation (46)).
S
SN
S
S
ArS
ArS
Ar
N
SS
ArCS2/ THF
rt ð46Þ
Two types of naphtho-fused 1,3-dithiol-2-thiones have been synthesized by the reaction of3,4,7,8-tetrachloronaphtho[1,8-cd:5,6-c0d0]bis(1,2-dithiol) with sodium trithiocarbonate<1998EJO1577> (Equation (47)).
SnTbt
Tip C CS
SS Sn
S
SSn
S
TbtTip
Tbt
Tip
R
R
R
: i. CS2(5 equiv.)
–70 °C
R = CH(SiMe3)2(Tbt) i-Pr(Tip)
Scheme 35
536 Functions Containing a Thiocarbonyl Group and at Least One Halogen
S SCl
Cl
Cl
ClS S
SR SCl
S
S
ClS SR
i. Na2S2C S
S
ii. R–X
R = alkyl, benzyl
S
ð47Þ
(vi) The organic chemistry of 1,3-dithiol-2-thione
1,3-Dithiol-2-thione, after lithiation with LDA, reacted with aryl carbaldehydes to afford thebisalcohol products in excellent yields. <2001CC369> (Equation (48)).
OHOHS
SS
Ar
Ar
S
SS
LDAAryl–CHO
ð48Þ
The diols were observed to slowly decompose at ambient temperature.Dihydro-1,3-dithiol-2-thionewas converted into apolycyclic sulfoniumsalt by reactionwithacetylenes
<2000HAC434> or benzyne (generated by the thermolysis of 2 equiv. of 2-carboxybenzenediazoniumchloride)<1999H103> (Equation (49)).
S
S
S
MeOOC COOMe
MeOOC COOMeS
SS
COOMe
COOMe
DMAD+
–
+ð49Þ
In the first case, the short-lived ylide was trapped; in the second case, the sulfonium salt wasisolated in good yield and was utilized as the starting material for the synthesis of a number ofmacrocylic rings of various ring size.
Direct cycloaddition of C60 to a diene, formed in situ by the thermal extrusion of SO2 from thecorresponding 1,3-dithiol-2-thione derivative, yielded the cycloadduct in 61% yield <1998JOC5201>(Equation (50)).
O2SS
SS
∆C60
S
SSC60+ Chlorobenzene ð50Þ
The C60 adduct was obtained as an inclusion compound of CS2, the application of heat underhigh vacuum gave the solvent-free thione.
(vii) Synthesis and chemistry of 1,3-dithiol-2-thione-4,5-dithiolates and their zinc complexes
1,3-Dithiol-2-thione-4,5-dithiolates, their zinc complexes, and other derivatives are useful startingmaterials for the preparation of �-donor molecules, precursors of organic conductors, and super-conductors. Methods for their preparation prior to 1995 have been reviewed <1995S215>. Analternative method for the preparation of 1,3-dithiol-2-thione-4,5-dithiolate, the zinc complex,and 4,5-ethylenedithio-1,3-dithiol-2-thione has been published <2000ZN231> (Scheme 36).
In the presence of a dienophile, the latter undergoes Diels–Alder-type pericyclic reactions<2000ZN231, 2001MI749, 1999TL8819>. 4,5-Ethylenedithio-1,3-dithiol-2-thione was readilyalkylated using 2-chloroethanol [or 3-bromopropanols, 2-(2-chloroethoxy)ethanol, etc.]
Functions Containing a Thiocarbonyl Group and at Least One Halogen 537
<2000S1615>, benzoyl chloride <1998S1615>, or 2-chloro-2-phenylacetophenone <2000CC2039>to form symmetric, dialkylation products. The monoalkylated product 4-alkylthio-1,3-dithiol-2-thione was obtained from the zinc complex of 1,3-dithiol-2-thione-4,5-dithiolate using electro-philic reagents in the presence of 3-picolylchloride hydrochloride or 4-picolyl chloride hydrochlorideor pyridine hydrochloride <2001OL1941>.
The treatment of the 4,5-diphenacyl-1,3-dithiol-2-thiones obtained in this manner withLawsson’s reagent in refluxing toluene led to the formation of six-membered heterocycles when Rwas Ph or 4-NO2Ph, and to the fused thiophene derivative when R was 4-MeOPh <1996TL2821>.
Similarly, the condensation of dicesium 2-thioxo-1,3-thiol-4,5-diselenolate with bisalkylatingpolythioethers in high dilution leads to a number of thiaselena crown compounds<1996LCS(P1)1995>.
The neutral 1,3-dithiol-2-thione-4,5-dithiolate complexes with organic antimony<2001IC2570> and ruthenium (NO, cyclopentendienyl) <1995ICA57>, ruthenium (¼O)<2001EJI1625>, dinuclear bis[dicarbonyl(cyclopentadienyl)]diiron(II) <2002JOM94>, cadmium<2000JA11007>, and palladium complexes <2002JCS(D)1377>, have been synthesized andcharacterized by X-ray diffraction.
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S
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Scheme 36
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542 Functions Containing a Thiocarbonyl Group and at Least One Halogen
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Functions Containing a Thiocarbonyl Group and at Least One Halogen 543
Biographical sketch
Professor Erich Kleinpeter obtained his diploma from the University ofLeipzig, Germany in 1970 and his Dr. rer. nat. in 1974 under thedirection of Professor Rolf Borsdorf. He continued teaching andresearch work at the University of Leipzig until 1979, when he spent ayear in the laboratories of Professor Rainer Radeglia at the Academy ofSciences, Berlin. Following this, he returned to Leipzig and habilitatedin 1981. After spending 1982–1985 as Associate Professor of OrganicChemistry at the University of Addis Ababa, Ethiopia, he moved to theUniversity of Halle-Wittenberg, Germany, where he was appointed adocent in spectroscopy, followed later by his appointment as Professorof Analytical Chemistry in 1988. In 1993 he took up his present positionas full Professor of Analytical Chemistry at the University of Potsdam,Germany. His research interests include all aspects of physical organicchemistry, in particular the application of NMR spectroscopy, quantumchemical calculations, and mass spectrometry to the examination andinvestigation of all kinds of interesting structures and new phenomena inorganic, bioorganic, and coordination chemistry.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 495–544
544 Functions Containing a Thiocarbonyl Group and at Least One Halogen
6.18
Functions Containing a Thiocarbonyl
Group Bearing Two Heteroatoms
Other Than a Halogen or Chalcogen
J. BARLUENGA, E. RUBIO, and M. TOMAS
Universidad de Oviedo, Oviedo, Spain
6.18.1 THIOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE NITROGENFUNCTION (AND NO HALOGEN OR CHALCOGEN FUNCTIONS) 545
6.18.1.1 Thiocarbonyl Derivatives with Two Nitrogen Functions 5456.18.1.1.1 From isothiocyanates 5456.18.1.1.2 From carbon disulfide 5536.18.1.1.3 From thiophosgene 5556.18.1.1.4 From thiocarbonyl transfer reagents 5556.18.1.1.5 From ureas 5566.18.1.1.6 Miscellaneous methods 5566.18.1.1.7 From thiocyanate salts and alkyl thiocyanates 5576.18.1.1.8 From thiocarbamoyl transfer reagents 5596.18.1.1.9 From sulfur-transfer reagents 561
6.18.1.2 Thiocarbonyl Derivatives with One Nitrogen and One Phosphorus Function 5646.18.1.2.1 From isothiocyanates 5646.18.1.2.2 From halothioamides 5666.18.1.2.3 From thiophosphinoyldithioformates 5676.18.1.2.4 From phosphonodithioformates 5676.18.1.2.5 Miscellaneous methods 567
6.18.2 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION 5686.18.2.1 Thiocarbonyl Derivatives with Two Silicon Functions 5686.18.2.2 Thiocarbonyl Derivatives with Two Phosphorus Functions 568
6.18.1 THIOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE NITROGENFUNCTION (AND NO HALOGEN OR CHALCOGEN FUNCTIONS)
6.18.1.1 Thiocarbonyl Derivatives with Two Nitrogen Functions
6.18.1.1.1 From isothiocyanates
The addition reaction of amines to isothiocyanates still continues to be the most general access toa wide array of thiourea derivatives (Equation (1)). In this section, some recent results concerningnew improvements as well as the application in the synthesis of molecules of interest arehighlighted.
545
N C SR1
NH
R3R2
S
NR2R3R1HN+
35–100%
R1 = alkyl, aryl
R2, R3 = H, alkyl, aryl
ð1Þ
Recently, Fuentes and co-workers <2002JOC2577> have reported the synthesis of thioureylenedi-C-nucleosides, a new type of dinucleotide analog, based on the addition of amines to isothio-cyanates (Scheme 1). Thus, the reaction of 30-amino-C-nucleosides with 30-isothiocyanato-C-nucleosides, which are in turn formed by reaction of the corresponding amine nucleosideswith thiocarbonyldiimidazole (TCDI), produces thioureylene di-C-nucleosides in very high toquantitative yields.
In a study focused on nonbiarylatropoisomers derived from carbohydrates, Palacios andco-workers <1999T4377> have described a facile access to chiral cyclic thioureas, specifically2-aryl-5-hydroxyimidazolidine-2-thiones, in moderate yields via addition of D-glucosamine toaryl isothiocyanates (aryl=2-FC6H4, 2-ClC6H4, 2-BrC6H4) (Scheme 2). A related reaction invol-ving D-fructosamines with different sugar isothiocyanates has been released <2000TA435>.
A high-yielding synthesis of guanidium derivatives from ethyl carbamate protected thioureaswas reported. The latter were in turn prepared by addition of amines to ethyl thiocyanato formate<2002TL565>.
Some modern techniques have been incorporated for the synthesis of the thiourea functionalgroup in order to overcome inherent difficulties found in the traditional methods. For instance,fluorous electrophilic scavengers for solution-phase synthesis have been successfully tested(Scheme 3) <2003TL2065>. Thus, fluorous isatoic anhydride 1 and isocyanate 2 are used asscavengers for amines in solution-phase synthesis of thioureas from isothiocyanates and excess ofprimary and secondary amines. The fluorous derivatives thus formed are readily separated fromthe reaction mixture by solid-phase extraction (SPE) over fluorous silica. The yields are in generalhigh, particularly with the fluorous scavenger 1, and the purity greater than 95% after thescavenging operation.
R2
OAc
SCN OR1
OAc
NH2O R2
OAc
NH O
O
R1
OAc
S
HNDMF oracetone
40 °C80–100%
+
R1, R2 = furan, imidazoline-2-thione,
pyrrole derivatives
Scheme 1
O
NH2
HOHO
OH
OH
NHNAr
S
HO H
OH
CH2OHOH
HO45 °C
+
Ar = 2-X-C6H4; X = F, Cl, Br
65–76%
EtOH–H2OArN=C=S
Scheme 2
546 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms
In addition, solid-state reactions have also become promising in the thiourea system synthesis.Thus, Kaupp and co-workers <2000T6899> have reported a series of solid-state reactionsbetween solid or gaseous amines and solid isothiocyanates to produce substituted thioureas inquantitative yields (100% yield, 53 examples) (Scheme 4). Except for washing in a few cases, thereaction does not require work-up, and allows for upscaling to the kilogram scale.
The high-pressure technique has been applied in the preparation of a number of thioureas derivedfrom aryl- and cyclohexyl-substituted isothiocyanates and different amino-substituted pyridinesand diazines (Scheme 5) <2002TL1035>. The yield of the high-pressure reaction is significantlyhigher (67%) than that of the thermal reaction (29% along with 38% of N,N0-diphenylthiourea) asit was found for the model components 4-aminopyridine and phenyl isothiocyanate.
Cyclic thioureas, particularly thiohydantoins, have attracted much attention mostly because oftheir biological properties. A practical eco-friendly procedure for the synthesis of 2-thiohydan-toins and 5-alkylamino-2-thiohydantoins has been developed recently using the solvent-less
PhNCS
S
NR1R2PhHN
O
N
O O
C8F17
NCOC8F17
R2 = alkyl
i. R1R2NH (1.5 equiv.)/CH2Cl2
ii. 1 or 2 (1.0 equiv.)/SPE
72–100% (from 1)
34–98% (from 2)
R1 = alkyl, H
1 2
Scheme 3
R1NCS
S
NR2R3R1HN
R3 = Me, H
100 %
R2R3NH
–30 °C to rt
solid state R1 = Ar, Me
R2 = Ar, Me, H
Scheme 4
N
NH2
N
HN NHPh
SPhNCS
NH2N NH2N NH2 N
NH2
N
N
N NH2N
N
NH2
NCS4-Me2N-C6H4-N=N
THF, reflux
29%THF, 40 °C, 0.6 GPa
67%
4-MeO-C6H4-NCS
+
THF, 40–80 °C0.6 GPa
47–95%
c-C6H11-NCS
Scheme 5
Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms 547
technique (Scheme 6) <2002TL8745>. Thus, the reaction of methylglycinate hydrochloride withisothiocyanates in refluxing diethyl ether or ethyl acetate gives rise to simple 2-thioxoimidazoli-din-4-ones, which are in turn transformed into 5-aminomethylidene derivatives by treatment withdimethylformamide diethylacetal (DMF-DEA) under solventless microwave irradiation.
Following this report, Dannhardt and co-workers have investigated the affinity to the glycinesite of the NMDA receptor of different indole-2-carboxylic acids having a thiohydantoinmethylsubstituent at C-3. The preparation of the target molecules involves reductive amination of ethyl3-formylindole-2-carboxylate with various amino acid esters followed by cyclization with isothio-cyanates and ester hydrolysis (Scheme 7) <2003JMC64>.
In the course of studies directed to the total synthesis of batzelladine alkaloids, Elliot andco-workers have reported a short access to substituted pyrrolo[1,2-c]pyrimidine-1-thiones(Scheme 8) <2002TL9191>. First, the necessary alkenyl pyrrolidine substrate is obtainedfrom glutamic acid in five steps. Then, the key annulation step is based on the previous reportby Kishi <1992JA7001> and is accomplished by the three-component reaction of alkenyl pyrro-lidine, silicon tetraisothiocyanate, and acetaldehyde at room temperature.
The group of Ortiz Mellet and Garcıa Fernandez have elegantly effected the preparation ofcyclooligosaccharide receptors of different ring size featuring a hydrophobic cavity. The macro-cyclic ring is constructed by double—inter and intramolecular—amine-to-isothiocyanate addition
N
N
R
S
O
H
N
N
R
S
O
HNH3N CO2Me
Cl
R-NCS
+
R = Me, Bu, Ph
TEA
Et2O or EtOAc
reflux Microwave
70–80 °C74–77%
no solvent
DMF–DEA
~96%
–
+
Scheme 6
NH
CHO
CO2EtCl
Cl
NH
CO2HCl
Cl N
NS R2
O
R1
Na(AcO)3BH
i. H2NCHR1CO2Me
ii. R2NCSEt3N/∆
iii. LiOH
R2 = Et, aryl
R1 = H, Me, Pri
Scheme 7
HO2C CO2H
NH2 N NH
S
CO2Et
TBSO
Me
N NH
S
CO2Et
TBSO
Me
NH
TBSO
CO2Et
Si(NCS)4
CH3CHO+
benzene
rt
Batzelladine A
54% 27%
Scheme 8
548 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms
(Scheme 9) <2002AG(E)3674>. Thus, the cyclodimerization of diisothiocyanate and diaminodisaccharides can be effected in moderate yield by mild heating in pyridine. The cyclotrimeriza-tion product is obtained from the acyclic thiourea dimer containing two isothiocyanate moieties,which is directly available by homocoupling of the corresponding diisothiocyanate disaccharide(vide infra, Scheme 14). Thus, the addition of the diamine disaccharide to the diisothiocyanatesubstrate affords moderate to high yields of the final cyclic pseudohexasaccharide.
The preparation of thiourea-functionalized resorcinarene cavitands, a novel class of neutralanion receptors, is also feasible starting from either isothiocyanate- or amine-containing cavitands(Scheme 10) <1998JOC4174>. Thus, the reaction of the tetrakis[aminomethyl]cavitands withalkyl and aryl isothiocyanates R2-NCS allows one to isolate the corresponding tetrakis[thio-ureamethyl]cavitands in 27–63% yield. Conversely, a new cavitand is obtained in two steps andmoderate overall yield by conversion of the aminocavitand into the isothiocyanate derivativefollowed by addition of the primary amine R3-NH2.
The use of macrocyclic thioureas as efficient anion receptors has been extended to a variety ofcyclophane-based structures. In this sense, different types of systems such as ortho–meta, meta–meta, and meta–para cyclophanes have been synthesized (Scheme 11) <2000JOC275>. Therequired starting materials are the 1,3-[bis(aminomethyl)]-4-,6-di-t-butylbenzene and the corre-sponding o-, m-, and p-bis(isothiocyanatomethyl)benzenes. The macrocyclization takes place inlow-to-high yields by heating at 60 �C in chloroform under high dilution conditions.
Other examples using thiourea receptors with a rigid xanthene spacer have been reported<1997T1647>. In addition, a series of fluorescent naphthylthioureas containing hydroxymethylgroups have been synthesized from naphthyl isothiocyanates and �-hydroxyamines<2003TL795>.
A new macrocyclic system containing oligoethyleneglycol chain and thiourea moieties has beenprepared and their binding ability toward dihydrogenphosphate anion and several cations inves-tigated (Scheme 12) <2003TL8183>. The synthesis of the target molecule involves the reaction ofthe tetraazathiapentalene derivative, prepared from the bis(pyrimidine-2-thione) and methyl iso-thiocyanate, with the corresponding diisothiocyanate followed by heating with base.
A number of thiourea-based compounds have been found to display an array of biologicalproperties. Since thioureas are known to raise the HDL cholesterol, some functionalized systemswith a thiourea moiety embedded in a functionalized side chain, for instance those havinga �-carboxylic acid group, have been prepared (Scheme 13) <2002BMC2439>. Thus, the additionof acyclic N,N-bis(trimethylsilyl)-�-amino acid esters or cyclic �-amino acid esters to aromaticisothiocyanates in methanol provides the corresponding N-thiocarbamoyl-�-amino acid esters inmoderate-to-high yields.
SCN NCS
H2N NH2
HNS
HN
NH
NHS
HNS
HN
NCS
NCS
S
NNHH
S N
N
H
H
SN
N
H
H
H2N NH2
ORO
ORRO
OR
RO
OR
+Pyridine
40 °C
Pyridine
40 °C
43%
40%
25–70%
=R = OAc, TMS, H
Scheme 9
Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms 549
Additional examples of biologically active thioureas derived from isoquinolines, pyrrolidines,and aryl ethylamines have been reported recently. Among them, thioureas with antispasmodicactivity <2001MI129> as well as thioureas with antagonist effect on a vanilloid receptor areworth noting <2003BMC197, 2003BMC601>.
On the other hand, isothiocyanates can be readily transformed into the corresponding symmetricN,N0-disubstituted thioureas upon treatment with pyridine water. The reaction is very well suitedfor those cases where the required amines are not accessible. The amine-free mechanism very likelyinvolves thiocarbamic anhydrides as reactive intermediates (Scheme 14) <1999S1907>. Thispractical procedure has been applied by the authors not only to the synthesis of simple andcarbohydrate-derived thioisocyanates, but also to more complex systems like cyclotetrahalins viamacrocyclization of the corresponding oligosaccharide isothiocyanates (Scheme 14)<2002AG(E)3674>.
O O
NH
S
NHR2
C5H11
O O
NH2
C5H11
O O
NH
S
NHR3
C5H11
O O
NCS
C5H11
Cl2CS
CH2Cl2
R3 =
NO2
O
R2 = aryl, t-octyl
4
4
R2NCS
CH2Cl2/CHCl3/THF
rt to reflux
54%
R3NH2
55%
4
4
4
27–63%
rt to reflux
Scheme 10
NH
HN
HN
NH OBu
OBu
S
S
t-Bu
t-Bu NH
HN
HN
NH
S
S
t-Bu
t-Bu OBu
OBu
NH
HN
HN
NH OBu
OBu
S
S
t-Bu
t-Bu
t-Bu
t-Bu
NH2
NH2
OBu
OBuSCN
SCN
OBu
OBu
SCN
SCN
BuO
OBu
SCN
NCS
CHCl3, high dilution, 60 °Cand or or
79%70% 31%
Scheme 11
550 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms
N
N
N
S
S
N
SMe
Me N
N S
N
N
SMe
S
Me
But
HN
HN
SO
O
O HN
HN
S
But
i. 3,6,9-Trioxaundecane-1,11-diisothiocyanatebenzene, reflux, 56%
ii. aq., KOH, EtOH, reflux, 69%
i, ii
=
Scheme 12
NH
ArS
NH CO2Et
RRCO2Et
(Me3Si)2NR R
ArNCS
MeOH
HN CO2Et N CO2Et
S
NH
Ar
ArNCSCH2Cl2
R = Me
R,R = –(CH2)3,5–
rt
rt
44–95%
Ar = 2X-5Y-C6H3 (X = Me, MeO; Y = Me, Cl)
Ar = 2-Me-5-Cl-C6H3
77%
Scheme 13
HNS
HN
NH
NHS
HNS
HN
NCS
NCS
O
ORO
O
ORRO
OR
RO
OR
RNCS
H2O
RNH
OH
SR
HN O
HN
S SR
– O C S
RNCS
NH
NH
RRS
SCN NCS40 °C
Pyridine/H2O
38% overall
=
rt to 60 °C
Pyridine/H2O
72–95%
(10:1)
(15:1)
60 °C
Pyridine/H2O
(10:1)
Scheme 14
Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms 551
During the last years some attention has been paid to the solid-phase synthesis of thioureas.For instance, the traceless synthesis of thioureas reported by Sim begins with the amination of thebromo-Wang resin followed by the addition of isothiocyanates. The thiourea unit was liberatedfrom the resulting resin-bound thiourea by treatment with 50% TFA in CH2Cl2 (Scheme 15)<2001SL697>. While the overall yields are high, the observed purity is rather low (13–51%). Ananalogous synthesis of isoxazoline thioureas using the chloro-Wang resin is also known<2000TL5069>.
Thiohydantoins are in turn available by solid-phase synthesis via polymer-supported amines asdepicted in Scheme 16. Thus, the sodium polystyrylsulfinate reacts with 2-choloroethanol to givea polystyrylethanol resin which is coupled with protected glycine to afford, after deprotection, thecorresponding resin-bound �-amino acid. The latter is added to phenyl isothiocyanate and theresulting thiourea subjected to basic or acid treatment to provide acyclic and cyclic thioureas,respectively <2001TL1973>.
Using a similar strategy, a high-yielding microwave-assisted synthesis of substituted thiohydan-toins has been accomplished. In this process, Fmoc-protected �-amino acids were coupled withHO-PEG-OH, deprotected, and reacted with isothiocyanates. After base-mediated cyclization, thethiohydantoin system was liberated from the matrix under microwave exposure <2003TL8739>.
The preparation of substituted isoxazolethiohydantoins has also been reported from hydro-xypropyloxymethylpolystyrene, alkynyl glycine, and isothiocyanates <1999JOC9297>. Moreover,it has been released an efficient solid-phase synthesis of quinazoline-2-thioxo-4-ones using Syn-PhaseTM lanterns supports <2000TL8333>.
R2NCSN N
H
R2S
R1
NHR1
BrCH2Cl2
NH
NH
R2R1S
CH2Cl2
R1NH2
rt rt
TFA-CH2Cl2 (1:1)
rt
68–92%
R1 = Prn
R2 = aryl
Scheme 15
SO2Na SO2
ONH2
O
SO2
ONHO
NH
SPh
NH
NH
PhS
HO2C
N
NPh
S
O
H
Bu4NI
DCC
ClOH
PhNCSDMF
dioxane
dioxane
20% overall
21% overall
ii. BOC-gly
iii. HCl
i.
90 °C
4 N NaOH
6 N HCl
Scheme 16
552 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms
The solid-phase addition of triazenes to isothiocyanates has been designed as an efficient routeto a new type of thioureas, which have been further elaborated into guanidines. The startingpolymer-bound triazenes are prepared by addition of primary amines to the T2* diazonium resin<2000OL3563>.
6.18.1.1.2 From carbon disulfide
The dithiocarbamic acid unit represents a suitable thiocarbamoyl transfer agent (see Section6.18.1.1.8). In most cases they are not commercially available and must be prepared. In thisway, Tomkinson and co-workers <1998TL1673> have reported a simple, high-yielding procedurefor the synthesis of thioureas in two steps from carbon disulfide, via amination of dithiocarbamicacids (Scheme 17). Thus, the reaction of primary or secondary aliphatic amines with carbondisulfide results in the formation of the corresponding dithiocarbamic acids, which then undergoamination upon treatment with primary or secondary 2,4-dinitrobenzenesulfonamides. Thismethod thus provides access to symmetrical and unsymmetrical di-, tri-, and tetrasubstitutedthioureas.
Very recently, an efficient synthesis of unsymmetrical diaminocarbene ligands via reduction ofunsymmetrical imidazolidine-2-thiones has been reported <2003AG(E)5243>. The methodologyfor the preparation of that type of cyclic thiourea was developed by Albrecht in 1994 by usinglithium N-butyl-N-lithiomethyldithiocarbamates, readily available from N-methyl butylamine andcarbon disulfide. The process consists of addition of the C-nucleophilic center of the dithiocarba-mate to the imine followed by cyclization (Scheme 18) <1994S719>.
The solid-phase synthesis has been accomplished by Mioskowski and co-workers<2000JCO75> by using a resin-bound dithiocarbamate moiety (Scheme 19). Thus, thetreatment of the Merrifield resin with a primary amine in the presence of carbon disulfideproduces the supported dithiocarbamate. Heating this dithiocarbamate in the presence of a
S
NR3R4R1R2N
R3R4NSO2ArCs2CO3
S
SHR1R2N
CS2
CH2Cl2
DMF, 80 °C
65–76%
–SO2
R1R2NHpyridine
(Ar = 2,4-dinitrophenyl)R1
= Me, H
R2 = Me, Bn, Ph
R3 = 4-MeOC6H4-CH2
R4 = MeOCH2CH2, H
Scheme 17
BuNHMeN
Bu
SLiS
LiNR1
R3
R2
NN
S
Bu R1
R3R2
R1 = H, Me, Pri, But
R2 = H, Me, Et, Ph
R3 = H, Me, Et, Pr, But, Ph
i. BuLiii. CS2
iii. BusLi –78 to –10 °C
R2, R3 = –(CH2)4, 5–
50–69%
Scheme 18
Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms 553
primary or secondary amine leads to the formation of the thiourea with the release of benzylthiolbound to resin. This method gives access to N,N0-di- and trisubstituted thioureas in good yieldsand with 90% of purity in most cases.
The synthesis of thioureas, as ‘‘en route’’ synthesis of modified chiral guanidines, has also beenachieved bymeans of carbon disulfide itself as the thiocarbonyl source. Thus, Ishikawa and co-workers<2000JOC7774> have obtained a number of unsymmetrical thioureas resulting from sequentialamination of CS2 with a primary amine—via the corresponding isothiocyanate—and an enantiopurediamine (Scheme 20). Application of this strategy to the synthesis of thioureido cyclodextrins by Ph3P-mediated coupling of CS2 (‘‘phosphinimine’’ approach) with cyclodextrin amines and primary amineshas been executed by Marsuda and co-workers <1999TL6581, 2003TL1533>.
Recently, the Italian group of Sartori, Ballini, and Maggi has carried out the carbon disulfide-mediated synthesis of thioureas in the presence of heterogeneous and reusable catalysts. Theyhave found that catalysts, such as Zn–Al HT(500) (a ZnO/Al2O3 composite) and MCM-41-TBD(1,5,7-triazabicyclo[4.4.0]dec-5-ene bound to mesoporous silica), are easily prepared and behaveefficiently in the synthesis of acyclic and cyclic symmetrical thioureas (Scheme 21)<1999JOC1029, 2002TL8445>.
S
S
NHR1
SH
Cl CS2
R1NH
S
NR2R3
R1 = alkyl, cycloalkyl, benzyl
R2 = H, Me
R3 = alkyl, benzyl
R2, R3 = –(CH2)5–
R1NH2Toluene
60 °C33–97%
EtiPr2N+
R2R3NH+
Scheme 19
CS2 R1HN N
S R2
NH2
R2HR2
H2NNH2
R2
R1 = alkyl, benzyl
CH2Cl2, rt
i. R1NH2, Et3N
ii.
CH2Cl2, rt
54–86%
R2–R2 = Ph, Ph (S,S); (CH2)4 (R,R); (CH2)4 (S,S)
Scheme 20
CS2
H2NNH2
RHN NHR
S
NN
S
HH
RNH2
R = alkyl, benzyl, aryl
Cat. = Zn-Al, HT (500) (100 °C, 57–100%)
MCM-41-TBD (90 °C, 57–91%)
90–100 °C
cat. cat.
90–100 °C
Scheme 21
554 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms
6.18.1.1.3 From thiophosgene
Another traditional methodology based on thiophosgene is still being used. Thus, cyclic, opticallyactive thioureas have been prepared and utilized as chiral guanidine precursors. In this way, thesynthesis of 1,3-bis(phenylethyl)imidazoline-2-thione with C2-symmetry and bicyclic prolinederived thiourea is shown in Scheme 22 <2000JOC7770>. Examples of application of thisprocedure to monosubstituted thioureas is reported in the synthesis of conformationally restrictedL-arginine and L-homoarginine derivatives <1999JOC3467>.
6.18.1.1.4 From thiocarbonyl transfer reagents
The double amination of appropriately designed thiocarbonyl synthons is currently another usefulsynthetic route for building up the thiourea functionality. In this sense, 1-(methyldithiocarbonyl)imidazole 3 and its N-methyl quaternary salt 4 have become efficient thiocarbonyl transferreagents for the synthesis of a diversity of thioureas (Scheme 23) <2000T629>. Thus, symmetricaldisubstituted thioureas are formed by refluxing an ethanol solution of either transfer reagent 3 or4 with primary amines in a molar ratio of 1:2; moreover, the use of diamines, e.g., 1,2-diamino-benzene and ethylenediamine, provides the corresponding cyclic thioureas. Unsymmetrical di- andtrisubstituted thioureas are accessible in very high yields by the sequential treatment of eitherdithiocarbonyl derivative 3 or 4 with 1 equiv. of a primary amine and 1 equiv. of a primary orsecondary amine, respectively, in refluxing ethanol.
ii. CSCl2, Et3N
Ph NN Ph
CH3
CH3H
H
NN Ph
OH
H
CH3
NN
SPh
CH3
NN PhPh
CH3 CH3SCSCl2
CH2Cl2, rt
CH2Cl2, Et3N
rt, 84%
i. LiAlH4
THF, 60 °C
47%
Scheme 22
RNH2 (2 equiv.)RHN
S
NHR
NN
S
SCH3 NN
S
SCH3H3C I
3 4
R1HN
S
NR2R3
R1 = Ph, benzyl, H
R2 = H, Me, aryl, c-C6H11
R3 = H, Me
R2, R3 = –(CH2)5–, –(CH2)2–O–(CH2)2–
3 or 4
40–96%
3 or 4
61–96%
ii. R2R3NH (1 equiv.)
EtOH/∆
EtOH/∆
i. R1NH2 (1 equiv.)
R = aryl, alkyl
EtOH/∆
+ –
Scheme 23
Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms 555
Alternatively, 1,1-thiocarbonyl diimidazole (TCDI) can be regarded as a very common thio-carbonyl transfer reagent to synthesize either symmetrical or unsymmetrical thioureas. Thus,various substituted N-pyridylthioureas with anti-HIV activity have been made accordingly, asillustrated in Scheme 24 <1999BMC2721>. The thioureas resulting from primary amines,TCDI, and 1,2-diaminoarenes are immediate precursors of valuable 2-(alkylamino)benzimidazoles<1999TL1103>.
Several papers dealing with the solid-phase synthesis of thioureas by thiocarbonyl transfer fromTCDI have also been published. For instance, Sun and co-workers <2001TL4119> havedescribed the preparation of 3,4-dihydro-1H-quinazolin-2-thiones (72–97% yield; 60–89% purity)from resin-bound 2-methylaminoanilines, which in turn can be made from Rink resin in threesteps (Scheme 25). In a similar way, the solid-phase syntheses of 1,3-disubstituted 2-thioxoquina-zoline-4-ones from resin-bound 2-aminobenzamides- <2001TL1749> and of bis-2-imidazolidi-nethiones from resin-bound tripeptides have been undertaken <2000OL3349>.
Recently, the synthesis of a novel C2-symmetric thiourea, as well as its application as ligand inpalladium-catalyzed coupling reactions, has been developed. In this case, (1(R), 2(S))-N,N0-(2-methylphenyl)-1,2-diaminocyclohexane was transformed into the corresponding imidazoli-dine-2-thione in 95% yield by condensation with thiophosgene <2004OL221>.
Pentafluorophenyl chlorothioformate has been used as thiocarbonyl transfer agent in thesolution and solid-phase synthesis of N-bromobenzyl-N0-sulfonylthioureas (Scheme 26)<2003JOC1611>. The use of the sulfonamide PbfNH2, as the key reagent to incorporate aTFA-labile guanidine protection group, greatly facilitates the solid-phase synthesis ofN,N0-substituted guanidine compounds.
6.18.1.1.5 From ureas
No relevant new work has been reported in this area since COFGT (1995) <1995COFGT(6)569>.
6.18.1.1.6 Miscellaneous methods
The transfer of both sulfur and nitrogen is also possible according to the report of Vallee andByrne which is summarized in Scheme 27 <1999TL489>. They have found that the treatmentof isonitriles with the dithioxo-bishydroxylamino molybdenum complex results in the formationof trisubstituted thioureas in good yields. The proposed reaction pathway is also described inScheme 27.
N
X
NH2 N
X
NH
NH
RS
X = Cl, Br, CF3
R = aryl, 1-cyclohexenyl
i. TCDIacetonitrile
ii. RCH2CH2NH2
DMF, 100 °C
Scheme 24
NH2
NH
O
NHR
NH
Fmoc
ii. TFA, CH2Cl2, rt N
NR
SO
H2N
H
i. TCDI, DMF, rt
72–97%
R = ArCH2, alkyl
Scheme 25
556 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms
6.18.1.1.7 From thiocyanate salts and alkyl thiocyanates
The thiocyanate salts represent an attractive alternative to isothiocyanates, particularly when theyare difficult to prepare, as it was demonstrated in the past. Recently, the general procedure hasbeen improved and the scope enhanced by Meckler and co-workers <2000S1569>. In this case,high yields of primary monosubstituted or symmetrical N,N0-disubstituted thioureas can bereached by refluxing potassium thiocyanate and amine hydrochloride in THF or xylenes, respec-tively (Scheme 28). This approach tolerates sterically bulky primary amines and the resultingthioureas are usually isolated by a simple filtration of the reaction mixture.
Ar NH2 Ar N NHPbfH
S
O
SO2
NH
NH
O S
NHPbf
CH2
CH2Cl2
i. ClCS-OC6F5, DIPEA
ii. PbfNH2, KOtBu
Rink amide
MBHA resin
Ar = Br Pbf =
70%
DMSO
Scheme 26
S
NEt2RHNN CR MoEt2N
O
S S
O
NEt2
Mo
S
O
NEt2
S
O
RN
Et2NMo
S
O
NEt2
S
Et2NO
RN
CHCl3
H2O
76–82%
(R = Bn, c-C6H11)
+
60 °C
–+
Scheme 27
R NH2.HCl
KSCN
THF
NH
NH
SR R
NH
NH2
SR +
reflux
Xylenes
reflux
66–96% 73–96%
R = alkyl, aryl, (R)-PhCH(Me)
Scheme 28
Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms 557
Glycopyranosylidene spirothiohydantoins have been prepared from per-O-acetylated 1-bromo-1-deoxy-�-D-glycopyranosacarboxamide, which is in turn available by radical-mediated bromina-tion of the corresponding glycopyranosyl cyanide (Scheme 29) <2001JMC2843>. Heating of anitromethane solution of the bromoamide and potassium thiocyanate in the presence of a smallamount of elemental sulfur resulted in the formation of the spirothiohydantoins in good yields.According to the authors, the reaction probably initiates by a single-electron transfer (SET) fromthiocyanate to the bromoamide and involves the coupling of the radicals in the solvent cage.
In a completely different approach, diastereomerically and enantiomerically pure 4-vinyltetra-hydro-1H-imidazole-2-thiones are synthesized from chiral aminoallyl thiocyanates (Scheme 30)<2002T1611>. Thus, these allyl thiocyanates, which are readily accessible from chiral ami-noallylic alcohols, lead to the observed cyclic thioureas by a thermal domino reaction consistingof a [3,3]-sigmatropic rearrangement followed by stereocontrolled intramolecular amine additionto the isothiocyanate functionality.
The one-pot synthesis of a series of N-substituted 1-amino-2,3-dihydro-1H-imidazole-2-thioneswas carried out starting from cheap materials such as hydrazines, �-bromoketones, and potas-sium thiocyanate and their anti-HIV and anti-SIV activity studied (Scheme 31) <2003JMC1546>.The mechanism proposed by the authors is outlined in the scheme and involves the [3+2]-cycloaddition of 1,2-diazadienes and isothiocyanic acid leading to an azomethine imine dipoleas the key step. Finally, the [1,4]-H shift would complete the mechanistic pathway. Alternatively,1,2,4-triazepine-3-thiones are formed by refluxing in DMF, a mixture of �,�-unsaturated ketonesand hydrazinediium dithiocyanate <2002TL7481>.
KSCN
OAcO
AcO
BrAcO
R
CONH2
OAcO
AcOAcO
R
NH
HN
S
O
MeNO2
S8
O
CONH2
SCN
80 °C
64–79 °C(R = CH2OAc, H)
SET Solvent cage
Scheme 29
R
NHBOCOMs
KSCNMeCN
R
NHBOC
S
N
R
NHBOC
NCS
NHN
S
BOC
R
Xylene
80 °C
R = Me, Et, Pri, Bn, Bni
80–89% ≥96% de
80 °C, 3 h
Xylene
3 h85–90%
2-hydroxypyridine(0.1 mol.%)
Scheme 30
558 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms
In a previous work, Schantl and Nadenık reported that using disubstituted bromoketones,instead of monosubstituted ones, the azomethine imine intermediate cannot stabilize by hydrogenmigration, so that a second dipolar cycloaddition to isothiocyanic acid occurs yielding efficientlyhexahydro-1H-imidazo[1,5-b][1,2,4]triazole-2,5-dithiones. Overall, the initially formed 1,2-diaza-diene undergoes two consecutive [3+2]-cycloaddition reactions to isothiocyanic acid in a ‘‘criss-cross’’ fashion (Scheme 32) <1998SL786>.
Moreover, Takahashi and Miyadai reported the ‘‘criss-cross’’ cycloaddition of 1,4-diazadienesto trimethylsilylisothiocyanates, as masked isothiocyanic acid, affording moderate yields ofperhydroimidazo[4,5-d ]imidazole-2,5-dithiones (Scheme 33) <1990H883>. Later, Potacek andco-workers <2002TL4833> undertook a detailed study of the ‘‘criss-cross’’ cycloaddition of1,4-diazadienes with mixtures of isothiocyanic acid and isocyanic acid, generated in situ frompotassium salts and acetic acid (Scheme 33). Although, mixtures of 2,5-dithione and 5-thioxo-2-onederivatives were formed, they found the isothiocyanic acid to be more reactive, the mixedderivatives being best obtained by slow addition of a 2:1 mixture of cyanate/thiocyanate salts tothe aldazine in acetic acid.
6.18.1.1.8 From thiocarbamoyl transfer reagents
Nitrosothioureas serve as a useful source of the thiocarbamoyl unit. Thus, the room temperaturetreatment of aliphatic primary and secondary amines with N-nitroso-1,3-dimethylthiourea(DMNT) leads to very high yields of N-methylthioureas. Starting with N-nitroso-1,3,3-tri-methylthiourea (TMNT), the analogous N,N-dimethylthioureas are produced again in high yields(Scheme 34) <1999TL1957>.
KSCN
NHN
S
HN
R2 R3
R1
R2
O
Br
R3 AcOH
R2
N
R3
SCN
HNR1
R2
N
R3
NR1
CS
NH NHN
S
N
R2 R3
R1
H
R1NHNH2
30 °C32–92%
+
–SCN
+–
Scheme 31
KSCN
R1
O
Br
R3R2AcOH NHN
S
N
R1 R3
Ph
R2
NNH
N
NH
S
Ph
R1R2
R3
SPhNHNH2
HNCS
R1 = H, R2
= R3 = Me (70%)
R1 = H, R2
= Me; R3 = Ph (80%, de = 48%)
R1 = Me, R2
= R3 = Me (91%)
+–
Scheme 32
Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms 559
As depicted in Scheme 35, methylN-aryldithiocarbamates were reported to undergo thiocarbamoyltransfer to aminopyridine derivatives <2001JHC457>. Thus, when 2-amino-3-carbethoxy-4,6-dimethylpyridine was reacted with various methyl N-aryldithiocarbamates in DMF, the expectedthiourea derivatives formed and spontaneously cyclized to 3-substituted 2-thioxo-5,7-dimethyl-pyrido[2,3-d]pyrimidine-4(3H)-ones in 55–69% yields.
Thioglycolic acid (a thiocarbamoyl transfer agent which is readily available from carbondisulfide, a primary or secondary amine and sodium chloroacetate salt) affords aminothiocarbonylhydrazines upon refluxing with hydrazine hydrate in a basic medium. Their thiosemicarbazoneswere synthesized by refluxing in water with an alcoholic solution of 5-nitrothiophene-2-carbox-aldehyde (Scheme 36) <2002BMC3475>. The overall process takes place with moderate yields andsome of the resulting products show significant antimoebic or antitrichomonal activity.
S
NNMe
N
Me
R1O
S
NR2R3NMe
R1
R2R3NH
acetonitrilert
DMNT (R1 = H)
TMNT (R1 = Me)
93–97% (R1 = H)
65–96% (R1 = Me)
R2 = Me, Et, Prn, Pri, Bun, c-C6H11
R3 = H, Me, Et, Prn, Pri, Bun
Scheme 34
NN
RR
N
NH
N
HN
S S
R
R
N
NH
N
HN
X
R
R
S
Me3SiNCSTHF
KOCN KSCNAcOH
R
NN
RR
rt
rt
R = c-C6H11, 4-MeOC6H4
24–53%
X = O/X = S
4-MeOC6H4
84/1396/4
76/24
1:2:1
+ +
c-C6H11
But
Scheme 33
S
SMeNH
Ar
N
Me
Me
CO2Et
NH2
DMF
N
Me
Me
CO2Et
NH NHAr
SN N
N
Me
Me S
ArO
H
Ar = C6H5, 3-Cl-4-F-C6H3,
X-C6H4 (X = 4-Me, 4-F, 4-Cl, 3-Cl)
55–69% +
Scheme 35
560 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms
6.18.1.1.9 From sulfur-transfer reagents
The direct introduction of sulfur from S8 into diaminocarbenes—the so-called Arduengo carbeneligands—can be regarded as a useful entry into cyclic thioureas. Thus, Bildstein and co-workershave reported the preparation of imidazolinethiones, imidazolethiones, and benzimidazolethionesby treatment of the corresponding azolium salts with base and elemental sulfur (Scheme 37)<1999OM4325, 1999JOM(572)177>.
The synthesis of 4-(4-fluorophenyl)-5-(pyridin-4-yl)imidazole-2-thiones, whose alkylthioimida-zoles are inhibitors of p38 MAP kinase, can be carried out in moderate to good yields by transferof sulfur from sodium (4-chlorophenyl)methanethiolate to 2-chloroimidazoles as outlined inScheme 38 <2002AG(E)2290>.
S
SR1R2N CO2HN2H4
.H2O
NaOH∆
S
NHNH2R1R2NSO2N CHO
S NO2
NNH
R1R2N
S
∆, 53–74%
R1 = alkyl, cycloalkyl
R2 = alkyl, H
R1, R2 = –(CH2)6–
Scheme 36
FcHNNHFc
NFcFcN
N
NFc
Fc
N
NFc
S
Fc
N
NS
CH3
Fc
N
NFc
CH3
X MeLi
S8, 44–56%
S8, 98%
X
or
KOtBu
(Fc = ferrocenyl)
– +
–
+
Scheme 37
N
NHet
Ar1
S
R1
Ar2
SCH2Ar2
N
NHet
Ar1
R1
ClN
NS
Het
Ar1
R1
H
Ar2CH2SNa (4.5 equiv.)
DMF/∆
Het = pyridin-4-yl
Ar1 = 4-F-C6H4
Ar2 = 4-Cl-C6H4
R1 = Ph, Prn, c-C6H11, pyridin-3-yl
51–80%
–
Scheme 38
Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms 561
The employment of ammonium sulfide for a convenient cyclization of �-cyano-�-(dichloro-methyleneimino)alkanoic acids, available from the corresponding isocyanides and chlorine, into5,5-disubstituted 2,4-dithiohydantoins has been described a few years ago (Scheme 39)<1998S1437>. The reaction is proposed to occur by addition of sulfide and cyclization to athiazole ring followed by ring opening and new closure.
In 1998 thioketones were first developed as efficient sulfur transfer agents towards azoleN-oxides providing a new synthetic method for the thiourea function (Scheme 40)<1998HCA1585>. Thus, substituted imidazole 3-oxides react with some thioketones (2,2,4,4-tetramethyl-cyclobuta-1,3-dithione, 2,2,4,4-tetramethyl–1-thioxo-cyclobutan-2-one, and adaman-tine-2-thione) to give imidazole-2(3H)-thiones in high yield. Triazole oxides can also betransformed equally well into triazolethiones.
Taking advantage of this procedure, Laufer and co-workers <2002AG(E)2290> have synthe-sized a structurally diverse imidazole thiones during their studies directed to develop new inhibi-tors of p38 MAP kinase with a 4,5-disubstituted alkylthioimidazole framework (Scheme 41).The required imidazole oxides are obtained in high yields by refluxing in ethanol a mixture of1-(4-fluorophenyl)-2-(pyridin-4-yl)hydroximinoethan-2-one and the corresponding 1,3,5-trisubsti-tuted hexahydro-1,3,5-triazine.
In the course of their studies of adenosine-derived monomeric building blocks for new oligo-nucleosides, Gunji and Vasella <2000HCA1331> showed the ability of N-phenylthiourea assulfur-transfer agent to 2-halogenoimidazoles (Scheme 42). Thus, the 2-chloro and 2-iodonucleosides were transformed into the corresponding thioxo nucleosides upon heating withN-phenylthiourea at 60 �C.
Molina and co-workers <2000TL4895> have reported a rather unexpected sulfur-transferreaction from carbon disulfide which is the basis of a new synthesis of dihydroquinazoline-2-thiones (Scheme 43). The process comprises the intramolecular heteroconjugate addition of
NS
S
HN
H
CO2R2R1
NN
S
H H
S CO2R2R1
NCl
Cl
NCCO2R2
R1(NH4)2S (2)
acetone, rt 58–75%
R1 = Me, Et, Bu
R2 = But
Scheme 39
S
N
NR1
R2
R3 ON
NR1
R2
R3 H
S
N
NPh
EtO2C ON
NPh
EtO2C H
S
SR
R
SR
RXS
CHCl3
SR
R
CHCl3
84%
65–96%
rt
rt
R1 = alkyl
R2, R3 = Me, Ph
(X = O, S)
+
+
= ;
–+
–+
Scheme 40
562 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms
aromatic carbodiimides bearing an o-substituted �,�-unsaturated carbonyl fragment promoted bythe carbon disulfide/tetrabutylammonium fluoride. The mechanism proposed by the authorsnicely accounts for the complex transformation and involves cyclization induced by attack ofthe S-nucleophile fluorodithioformate, generated from CS2-TBAF, followed by thioacyl fluoridehydrolysis and fragmentation to the thione group and C(S)O.
Finally, N,N-unsubstituted thioureas are accessible in moderate-to-high yield by sulfur transferfrom LiAlHSH, generated in situ by mixing LAH and sulfur, to chloroamidines, as depicted inScheme 44 <2001TL6333>.
O NN
N
NOR1
R2
X
O O
NHBz
O NNH
N
NOR1
R2
S
O O
NHBz
PhHN NH2
S
C C
toluene, 60 °C82–98%
R1 = Et3Si
R2 = Me3Si
X = Cl, I
Scheme 42
R2
N C NR1
O
N
N
R2
O
R1
SH
N
N
R2
O
R1
SF
S
S
SF
H2O
S C O
TBAFBu4N
Bu4N
CS2/ TBAF (4:1)
25 °C
R1 = Ar, Bn
R2 = Fc, OMe
40–50%
–
–
– +–
+
Scheme 43
SS
N
NHet
ArO
R
N
NHet
Ar
S
R
H
Het O
NOHAr
(CH2=NR)3
CHCl3, rt
Het = pyridyn-4-yl
Ar = 4-fluorophenyl
R = Me, Prn, c-C3H7, R2N(CH2)2, 3, RO(CH2)3
60–98%
EtOH/∆
50–89% –
+
Scheme 41
Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms 563
6.18.1.2 Thiocarbonyl Derivatives with One Nitrogen and One Phosphorus Function
6.18.1.2.1 From isothiocyanates
The addition of the P�H bond of phosphines to isothiocyanates, as well as the lone pair ofsubstituted phosphines, continues to be the most valuable method for preparing phosphinothio-formamides. For instance, bis(2-phenethyl)phosphine adds to 2-(vinyloxy)ethyl isothiocyanateunder thermal reaction conditions to produce the expected N-(2-vinyloxyethyl thiocarbamoyl)phos-phine in excellent yield. Similarly, the addition of the phosphine oxide analog to the isothiocya-nate and stirring in refluxing benzene results in the formation of the correspondingN-(2-vinyloxyethylthiocarbamoyl)phosphine oxide (Scheme 45) <1999JOU212>.
Phosphines bound to transition metals have frequently been reacted with isothiocyanates inorder to effect structural modification on the coordination sphere in phosphine-containing metalcomplexes. Malisch and co-workers <1998ZN(B)1084> have prepared various P-mesitylfer-rio(thiocarbamoyl)phosphines by reaction of P-mesitylferriophosphine with alkyl and phenylisothiocyanates (Scheme 46). The thiocarbamoylphosphines thus obtained were in turn P-alky-lated with alkyl halides or oxidized with elemental sulfur. In addition, the authors communicatedthat the ferrio-(t-butyl)phosphine analog reacts with 2 equiv. of methyl and ethyl isothiocyanateto produce P-thiocarbamoylphosphametallacycles (Scheme 46). The formation of these adductscan be rationalized by formal [3+2]-cyclization of isothiocyanate and the metal complex, via thephosphine and CO ligands, followed by insertion of the second molecule of heterocumulene intothe P�H bond <1998JOM(568)247>.
Molybdenum and tungsten phosphenium complexes Cp(CO)2M¼PH-t-Bu undergo a [2+2]-cycloaddition reaction to alkyl isothiocyanates furnishing the four-membered phosphametalla-cycles. Furthermore, insertion of the isothiocyanate into the P�H bond of these systems occursand the corresponding thiocarbamoyl phosphine derivatives are obtained in high yields(Scheme 47) <2000JOM(595)285>. In a closely related process, deprotonation of the dinuclearphosphine complex shown in Scheme 47, followed by addition of phenyl isothiocyanate andnitrogen protonation gives the expected complex in 85% yield <2000OM984>.
The ferrio-diphenylphosphine Cp(CO)(PMe3)Fe-PPh2, formed from Cp(CO)2Fe-PPh2 by CO/PMe3 ligand exchange, readily adds to methyl isothiocyanate giving rise, after protonation withtriflic acid, to the cationic open-chain thiocarbamoylphosphine iron complex (Scheme 48)<1998ZN(B)1077>. Structurally related complexes of iron and ruthenium, formed in situ bydeprotonation of their cationic precursors with KO-t-Bu, add to methyl isothiocyanate to
S
NHR1R2P
O
R2PHN C SR1
R2P
O
HS
NHR1R2P C6H6, reflux, 95%70 °C, 90%
R1 = CH2=CH-O-CH2CH2
R = PhCH2CH2
Scheme 45
HCl S
NH2NR
R
NH
SHNR
R
NH
ClNR
R
LiAlHSH
R = Me, Et
R-R = –(CH2)4,5–
THF, 0 °C 51–89%
Scheme 44
564 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms
generate an open-chain adduct, which suffers further cyclization by means of nucleophilicaddition to a carbonyl ligand (Scheme 48) <1998JOM(568)241>. The corresponding acyclicaddition product would be available by acid treatment.
R1NCSCp(CO)2Fe P
H
Mes S
P NHR1
Mes
Cp(CO)2Fe
S
P NHR1
Mes
Cp(CO)2FeR2
S
P NHR1
S
Cp(CO)2FeMesS
PFe
N S
R
O
Cp
OC
S
NHR
But
XR2X
R1 = Me, Et, Ph
Mes = mesityl
toluene25 °C, 69–76% R = Me, Et
Cp(CO)2Fe-PH-But2RNCS
Scheme 46
[M] PH
But
Et3N[M]
S
P
N
SNHR
R
But
P
Cp(CO)2Mo Mo(CO)Cp
P
PHPh2
P
Cp(CO)2Mo Mo(CO)Cp
P
Ph2P
S
NHPh
RNCS
[M]
S
P
N R
HBut RNCS
[M] = Cp(CO)2Mo, Cp(CO)2W
R = Me, Et, But
toluene25 °C
74–93%
i. DBU
ii. PhNCS, 25 °C
iii. HBF4, 85%
Scheme 47
PM
N S
Me
O
Cp
OC R2
R1
X
S
NHMeCp(Me3P)(CO)FePPhPh
S
NHMeCp(CO)2FePPhPh
HXX
KOBut
toluene25 °C, 68–83%
Cp(CO)2M-PHR1R2
M = Fe, RuR1
= But, Pri, Ph
R2 = But, Pri, Ph
Cp(CO)(PMe3)FePPh2
i. MeNCS
ii. TFA
M = FeR1
= PhR2
= Ph98%
Me-NCS
+
+
–+
–
Scheme 48
Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms 565
Majoral and co-workers <1999OM1882, 2000CEJ345> have carried out an extensive study onthe reactivity of bi- and tricyclic �-zirconated phosphanes and various cumulenes, e.g., isothio-cyanates (Scheme 49). Thus, �-phosphinozirconacycles and methyl and phenyl isothiocyanatesafford stable zwitterionic tri- and tetracyclic five-membered anionic zirconium complexes inmoderate-to-high yields.
Interestingly, the P�Si bond is capable of inserting into the C¼N bond of isothiocyanates inthe same way as does the P�H bond. This makes it feasible to prepare unconventional systemssuch as thiocarbamoyl phosphaalkenes, as reported by Weber and co-workers (Scheme 50)<1998OM3593>. The reaction of the phosphaalkene (Me2N)2C¼P-SiMe3 with phenyl isothio-cyanate in pentane at low temperature furnishes the expected adduct in 72% yield.
Cyclic systems, such as thioxoazaphospholes, have recently been described by Ruiz and co-workers(Scheme 51) <2002CEJ3872>. They started with the diphosphanyl ketenimine, which was firsttransformed into the monooxidized derivative by crystallization-induced cyclodimerization, followedby H2O2 oxidation and thermal dedimerization. The oxidized diphosphanyl ketenimine behaves as a1,3-dipole towards ethyl isothiocyanate affording the [3+2]-cycloadduct in 70% yield.
6.18.1.2.2 From halothioamides
A facile synthesis of diphenylphosphino-N,N-dimethylthioamide, a simple and useful ligandin organometallic chemistry, has been achieved in moderate yield and comprises thetreatment of sodium diphenylphosphide with dimethylthiocarbamoyl chloride (Scheme 52)<2001JCS(D)309>.
ZrCp Cp
PPh2ZrCp
Cp N
PPh2
SR
ZrCp Cp
PPh ZrCp
Cp N
P
PhS
Ph
PhNCS
RNCS
toluene
– 40 °C, 91%
toluene25 °C, 53–73%
R = Me, Ph
+–
Scheme 49
PMe2N
Me2NSiMe3 P
Me2N
Me2N
S
NPh
SiMe3PhNCS
pentane–30 °C, 72%
Scheme 50
C CPh2P
Ph2PN Ph
O
EtNCS
PN
N
Et
SPhPh
Ph2PPh
O
C CPh2P
Ph2PN Ph
i. Crystall.
ii. H2O2
iii. Toluene reflux
81%
toluene reflux70%
Scheme 51
566 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms
6.18.1.2.3 From thiophosphinoyldithioformates
No relevant new work has been reported in this area since COFGT (1995)<1995COFGT(6)569>.
6.18.1.2.4 From phosphonodithioformates
A large number of phosphonate derivatives have been reported by amination of methyl phos-phonodithioformates with primary and secondary amines as well as with ammonia (Scheme 53)<1994ZOB1639, 1994PS119>.
6.18.1.2.5 Miscellaneous methods
Renard and Mioskowski have utilized various phosphorus reagents to create phosphorus–sulfurbonds. Accordingly, the synthesis of a number of phosphonothioates is readily achieved by thereaction of the phosphorus precursors with alkylthiocyanates in the presence of the hindered,nonnucleophilic base phosphazene P4-t-Bu (Scheme 54, via A) <2002CEJ2910>. Unexpect-edly, the heating of ethoxyphenyl phosphinate with cyclohexylthiocyanate in the presence ofdiisopropylethylamine, instead of phosphazene, results in the exclusive formation of the (cyclo-hexylamine)thioxomethyl phosphinate derivative (via B). Obviously, the formation of the thio-carbamoylphosphine derivative requires that the phosphorus–carbon bond formation be precededby the thermal isomerization of cyclohexylthiocyanate to cyclohexylisothiocyanate.
S
NMe2Ph2PPh2PH
S
NMe2Cl
i. Na / THF
ii.
55%
THF, 25 °C
Scheme 52
R1 = R2
= H; R1 = H, R2
≠ H; R1, R2 ≠ H
S
SH(RO)2P
O
S
NR1R2(RO)2P
O
R1R2NH
Scheme 53
S
NH-c-C6H11PO
EtOPh
C NSc-C6H11
PO
PhOEt
S c-C6H11
Pr2NEt
DMFPO
PhOEt
H
110 °C78%
82%
Phosphazene
+
via A
via B
P4-t-Bu
Scheme 54
Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms 567
According to Morita and co-workers <1999TL2327>, different phosphine carbothioamidesare available in moderate yields by heating tetrazolylsulfinylmethyl(dimethyl)phosphine oxide inthe presence of primary and secondary amines (Scheme 55). The resulting compounds are thoughtto be formed by the addition of amines to the sulfine formed initially, followed by elimination ofwater.
6.18.2 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION
This class of compounds is very rare in the literature. In fact a few examples of silicon-containingderivatives were collected in the COFGT (1995) report. In the present update review, isolatedsystems containing two phosphorus functions and two silicon functions are given.
6.18.2.1 Thiocarbonyl Derivatives with Two Silicon Functions
Bis(trimethylsilyl)thioketone S-oxide represents certainly an island in the context of this sortof silicon functionality. In this particular case, tris(trimethylsilyl)methyllithium was reactedwith SO2 in THF to provide that functional system in 41% yield (Scheme 56)<2000CJC1642>.
6.18.2.2 Thiocarbonyl Derivatives with Two Phosphorus Functions
Taking advantage of the reversible S�S bond breaking and bond formation in dinuclear com-plexes of Mn(I) containing the disulfide function, Ruiz and co-workers <2001AG(E)220> havereported a method for accessing a mononuclear (diphosphanylthioketone)manganese complex(Scheme 57). Thus, the starting disulfide-containing dinuclear complex 5 transformed instanta-neously into the sulfenyl iodide mononuclear complex 6 upon treatment with 1 equiv. of iodine.Further iodide abstraction by using either excess of iodine or TlPF6 produces the desired diphos-phanylthioketone complex 7. The direct conversion of the disulfide 5 into 7 was accomplished byoxidation of the sulfur–sulfur bond with 2 equiv. of AgBF4.
(Me3Si)3C-Li SO2
THF
S
SiMe3Me3Si
O
+
41%
Scheme 56
N N
NN
Ph
SO
PMe2
OS
R1R2N PMe2
O
N N
NN
Ph
HS
H PMe2
O
O
R1R2NH
dioxane70 °C
50–53%
-R1R2NH–H2O
Scheme 55
568 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms
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(CO)4MnP
PS
PhPh
Ph Ph
(CO)4MnP
PS
PhPh
Ph Ph
I
(CO)4MnP
PS
PhPh
Ph Ph
I2
CH2Cl2
AgBF4
CH2Cl2
5 6
7
I2 TIPF6
2
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2
–Ag
40%
or
+
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Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms 569
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570 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms
Biographical sketch
Jose Barluenga studied chemistry at the Uni-versity of Zaragoza and received his doctoratein 1966. He spent three and a half years as apostdoctoral research fellow of the MaxPlanck Gesellschaft at the Max Planck Insti-tut fur Kohlenforschung (Mulheim a.d. Ruhr,Germany) in the group of ProfessorH. Hoberg. In 1970 he became Research Asso-ciate at the University of Zaragoza where hewas promoted to Associate Professor in 1972.In 1975 he moved to the University of Oviedoas Professor in Organic Chemistry, where heis currently Director of the Instituto Universi-tario de Quımica Organometalica ‘‘EnriqueMoles.’’ His major research interest is focusedon developing new synthetic methodologies inorganic chemistry by means of organometallicreagents as well as iodine-based systems.
Eduardo Rubio (Logrono, Spain, 1959)received his B.A. degree in Oviedo and gothis Ph.D. under the supervision of ProfessorsBarluenga and Tomas in 1989. He carried outpostdoctoral studies at MIT (Alex Klibanov,enzymes in organic solvents, 1989–1990) andat the University of California, Berkeley(Peter Vollhardt, organic synthesis mediatedby organometallic reagents, 1990–1991). Hereturned to the University of Oviedo and gota position as Profesor Titular in 1996. From2000 he is the secretary of the Instituto Uni-versitario de Quımica Organometalica ‘‘Enri-que Moles,’’ where he continues his research.His main research interests are synthetic andmechanistic chemistry and the application ofNMR to the study of reaction mechanisms.
Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms 571
Miguel Tomas received his B.A. degree in chemistry from the Universityof Zaragoza in 1974 and his Ph.D. degree from the University of Oviedoin 1979. He was a postdoctoral fellow (1981–1983) in the research groupof Professor A. Padwa at Emory University (Atlanta, USA) working on1,3-dipolar cycloadditions. Then, he returned to the University ofOviedo where he was appointed Profesor Titular in 1985 and promotedto Professor of Organic Chemistry in 1996. His major research encom-passes the use of transition metal reagents, particularly metal carbenecomplexes, as flexible intermediates in organic synthesis and the designof new metal-catalyzed processes.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 545–572
572 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms
6.19
Functions Containing
a Selenocarbonyl or Tellurocarbonyl
Group—SeC(X1)X2 and TeC(X1)X2
L. J. GUZIEC and F. S. GUZIEC, Jr.
Southwestern University, Georgetown, TX, USA
6.19.1 OVERVIEW 5736.19.2 SELENO- AND TELLUROCARBONYL FUNCTIONS CONTAINING AT LEAST ONE
ATTACHED HALOGEN 5746.19.2.1 Seleno- and Tellurocarbonyl Compounds Containing Two Attached Halogen Atoms 5746.19.2.2 Seleno- and Tellurocarbonyl Compounds Containing One Attached Halogen Atom 574
6.19.3 SELENOCARBONYL FUNCTIONS CONTAINING AT LEAST ONE ATTACHEDCHALCOGEN (AND NO HALOGENS) 576
6.19.3.1 Dialkoxy-substituted Selenocarbonates (RO)2C¼Se 5766.19.3.2 Dithio-substituted Selenocarbonates (RS)2C¼Se 5766.19.3.3 Diseleno-substituted Selenocarbonates (RSe)2C¼Se 5786.19.3.4 Selenocarbonyl Functions Flanked by Two Different Chalcogen Atoms RX(C¼Se)Y 5806.19.3.5 Selenocarbamates RO(C¼Se)NHR, RS(C¼Se)NHR, RSe(C¼Se)NHR, RTe(C¼Se)NHR 581
6.19.4 FUNCTIONS CONTAINING AT LEAST ONE NITROGEN FUNCTION(AND NO HALOGEN OR CHALCOGEN FUNCTIONS) 584
6.19.4.1 Selenoureas (R2N)2C¼Se 5846.19.4.2 Other Cyclic N(C¼Se)N Compounds 5886.19.4.3 Telluroureas (R2N)2C¼Te 590
6.19.5 HYPERVALENT SELENOCARBONYL COMPOUNDS OF THE TYPE Se¼C(X)X0 591
6.19.1 OVERVIEW
As previously reported in chapter 6.19, COFGT (1995) <1995COFGT(6)587>, seleno- and tell-urocarbonyl derivatives of common carbonyl-based functional groups are much less well knownthan their corresponding oxygen or sulfur analogs. The comparative rarity of the seleno- andtellurocarbonyl compounds has been primarily due to their decreased stability as a result of poor�-overlap in C¼Se and C¼Te bonds. In the period 1993–2003 ingenious use of new reactionsand novel reagents have made previously rare structures much more readily available for inves-tigation. Particularly noteworthy in this period are reports of hypervalent halogen adducts ofselenocarbonyl compounds, a topic not originally covered in COFGT (1995)<1995COFGT(6)587>.
573
6.19.2 SELENO- AND TELLUROCARBONYL FUNCTIONS CONTAINING AT LEASTONE ATTACHED HALOGEN
6.19.2.1 Seleno- and Tellurocarbonyl Compounds Containing Two Attached Halogen Atoms
Compounds containing a halogen atom directly attached to a seleno- or tellurocarbonyl functionremain quite rare <1995COFGT(6)587>. Both selenocarbonyl difluoride 1 and tellurocarbonyldifluoride 2 have been prepared by careful reaction of mercury salts with Lewis acid. Both ofthese compounds are unstable and rapidly dimerize. The reactivity of the tellurocarbonyl com-pound greatly exceeds that of the corresponding selenocarbonyl species. An improved method forthe preparation of monomeric tellurocarbonyl difluoride involves pyrolysis of the stannyl telluride(Equation (1)) <1993JCS(D)2547>. Dimerization to the corresponding ditelluretane rapidlyoccurs at temperatures above 77K. Co-condensation of 1 and 2 affords the mixed selenium–tellurium dimer. In situ generated tellurocarbonyl difluoride can also be trapped as its cycloaddi-tion product with 2,3-dimethylbutadiene (Scheme 1).
F
FSe
F
FTe
Cl
ClSe
1 2 3
Me3SnTeCF3
F
FTe
Te
Te
F
F
F
F
i. FVP, 280 °C
i
50–60%
> –196 °C
ð1Þ
Selenophosgene 3 has been suggested as an intermediate in Willgerodt–Kindler-type reactionsof trichloroacetic acid or chloroform with base and elemental selenium in the presence of aminesto form selenoureas <1996BCJ2235> (see Equation (30)).
6.19.2.2 Seleno- and Tellurocarbonyl Compounds Containing One Attached Halogen Atom
N,N-Dimethylselenocarbamoyl chloride 4 can be prepared quantitatively by treatment of dichloro-methylene dimethyliminium chloride with lithium aluminum dihydroselenide (Equation (2))<2002JOC1008>. This selenocarbamoyl chloride is an extremely useful reagent for the prepara-tion of diselenocarbamates, thioselenocarbamates, and selenoureas (see Sections 6.19.3.5and 6.19.4.1). The conversion of other dialkyliminium salts into the corresponding selenocarba-moyl chlorides should significantly simplify the preparation of a variety of other interestingselenocarbonyl compounds.
F
FTe
Te
Se
F
F
F
F
F
FSe
Te
FF
Scheme 1
574 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group
LiAlHSeH, 0 °C
QuantitativeMe2N C Cl
SeMe2N CCl2 Cl
4
ð2Þ
A number of unstable selenocarbonyl fluorides can be prepared by treatment of perfluorinatedmercuric selenides with diethylaluminum iodide or aluminum iodide (Equation (3)) <1991CB51>.These compounds rapidly polymerize, but the polymers upon heating can be converted to themonomeric or dimeric materials. The monomeric selenocarbonyl compounds can be trapped bycycloaddition with cyclopentadiene (Scheme 2).
R F
Se
R F
Se
n35 – 45%
(RSe)2Hg
R = CF3CF2CF2–, CF3CF2–, CF3–
R = CF3CF2–, CF3–, CF3Se–
Et2AlI
ð3Þ
Flash vacuum pyrolysis (FVP) of perfluorinated trimethyltin tellurides affords isolabletellurocarbonyl fluorides which dimerize at low temperature to the corresponding ditellure-tanes 5 (Equation (4)) <1996JCS(D)4463, 2000JCS(D)11>. The tellurocarbonyl fluorides canalso be trapped as their cycloadducts with dienes (Equation (5)) <1997PS(124)413>.Although no tellurocarbonyl analogs of acyl chlorides have been reported, the ‘‘dimeric’’dichloroditelluretane 6 can be isolated by reaction of the difluoro compound with borontrichloride (Equation (6)).
Me3SnTeRF R1
Te Te
Te F
R1
F
R1FVP > –196 °C
49–64%
5R = CF3CF2–,
CF3CF2CF2–,
CF3(CF2)2CF2–
R1 = CF3–,
CF3CF2–,
CF3CF2CF2–
ð4Þ
Te
CF2CF3
FMe3SnTeCF2CF2CF3 CF3CF2 F
Te160 °C
75%
ð5Þ
Te
Te
F
CF3CF2
F
CF2CF3
Te
Te
Cl
CF3CF2
Cl
CF2CF3
– 40 °C to 22 °CBCl3
82%6
ð6Þ
Se
R
F
R F
Se
R F
Se
Se
SeF
R R
F∆
n
R = CF3CF2–, CF3–
Scheme 2
Functions Containing a Selenocarbonyl or Tellurocarbonyl Group 575
6.19.3 SELENOCARBONYL FUNCTIONS CONTAINING AT LEAST ONE ATTACHEDCHALCOGEN (AND NO HALOGENS)
6.19.3.1 Dialkoxy-substituted Selenocarbonates (RO)2C¼Se
Dialkoxy-substituted selenocarbonyl compounds remain quite rare in the literature<1995COFGT(6)587>. O,O-Diethylselenocarbonate 7 has been prepared from tetraethylortho-carbonate by the use of bis(dimethylaluminum)selenide (Equation (7)) <1992TL7865>. Attemptsat using this reagent for the direct conversion of the carbonyl group to the selenocarbonyl groupin other related compounds were unsuccessful.
(EtO)4C EtO OEt
Se
+
7
74%
Toluene, dioxane80 °C
(Me2Al)2Se ð7Þ
6.19.3.2 Dithio-substituted Selenocarbonates (RS)2C¼Se
A variety of synthetic routes have been available for the preparation of cyclic dithio-substitutedselenocarbonates, important precursors for the synthesis of tetrathiafulvalenes<1995COFGT(6)587>. A number of routes for the preparation of these selenocarbonates startfrom the corresponding thiocarbonyl compounds. Selective S-alkylation followed by treatmentwith sodium hydrogen selenide affords the desired selenocarbonyl derivatives in good yield(Equation (8)) <1994JOC5324, 1998JOC8865>. Some additional examples of this transformationin the preparation of various complex dithio-substituted selenocarbonates have also appeared(Equation (9)) <1997JOC1903, 1998JOC8865>. The utilization of the selenocarbonate–dieneintermediate 8 appears to be a particularly interesting approach for the introduction of thedithioselenocarbonate moiety into complex molecules (Scheme 3) <2002JMAC2137>.
S
SS
S
S
O
O
Ph
Ph
S
SSe
S
S
O
O
Ph
Ph
i. CF3SO3CH3ii. Se, NaBH4, PhCOCl
76%
ð8Þ
S
SS
S
SSe
i–iii
i. CF3SO3Me, 91%; ii. Se, H2O, NaBH4; iii. AcOH, toluene, 59% for two steps
ð9Þ
The thiocarbonyl group of a cyclic trithiocarbonate group can also be converted tothe corresponding selenocarbonyl moiety using triethyl orthoformate in the alkylationstep (Scheme 4) <1994CHE652>. Subsequent base promoted cyclization affordedthieno[2,3-d]-1,3-dithiol-2-selone 9. Related heterocyclic dithioselenocarbonates could bereadily incorporated into the corresponding complex tetrathiafulvalenes <1992CHE945,1994CHE1116>.
A variety of complex heterocyclic dithioselenocarbonates have also been prepared using the reac-tion of N,N-dialkyldithiocarbamate salts with sodium hydrogen selenide (Schemes 5 and 6)<1992CHE941, 1993CHE1316, 1993CHE1432>.
576 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group
S
SS
SMeO
O
MeO
O
S
SSe
SMeO
O
MeO
O
S
S
SMeO
O
OHSe
i. HC(OEt)3, BF3·Et2O
ii. NaHSe
27%
i. NaOMe; ii. H+
i, ii
Quantitative
9
Scheme 4
HN
N
O
S
SNEt2
H2N
+
ClO4
HN
N
O
S
SSe
H2N
HN
NH
OS C NEt2
Se
SH2N +76%
i, ii
50%
i. Na2Se; ii. AcOH; iii. HCl, AcOH, heat; iv. DMF, pyridine, H2O
iii, iv
Scheme 5
S
SSe
S
SS
HOHO S
SSe
BrBrS
SSe
HOHO
S
SSe
C60
i–iii iv
v
25%
i. MeI, THF, 91%; ii. Se, H2O, NaBH4; iii. AcOH, toluene;iv. PBr3, THF, CCl4; v. KI, 18-crown-6, toluene
58%76%
8
Scheme 3
N
N
O
O OMe
Me S C NEt2
S
N
N
O
OMe
Me
S
SNEt2+
N
N
O
OMe
Me
S
SSe
ClO4
i. Conc. H2SO4
ii. NaClO4
i
66%
i. Na2Se, H+
Scheme 6
Functions Containing a Selenocarbonyl or Tellurocarbonyl Group 577
The metallation–chalcogenation sequence performed on the mixed sulfur–selenium substitutedthione 10 leads to a ‘‘Dimroth rearrangement’’ affording the selenocarbonyl complex, which can befurther transformed into other selenocarbonate derivatives (Scheme 7) <1992JOM(427)213>.
6.19.3.3 Diseleno-substituted Selenocarbonates (RSe)2C¼Se
Cyclic triselenocarbonates are important intermediates in the synthesis of tetraselenafulvalenederivatives and numerous methods have been used in the preparation of these compounds<1995COGFT(6)587>. A novel approach to the preparation of the unsymmetrical triselenocar-bonate 11 involves metallation of the protected acetylene followed by consecutive treatmentof the lithium salt with selenium, carbon diselenide, and methyl iodide (Equation (10))<1998JOC8865>. A variety of other triselenocarbonate derivatives <1997SL319> includingbridged bis(1,3-diselenole-2-selones) 12 have also been prepared using this procedure(Equation (11)) <1998AG(E)619>.
Se
SeSe
SeMe
OTHPOTHP i–iv
i. BunLi, TMEDA, THF, –70 °Cii. Se, 0 °Ciii. CSe2, Se, –70 °Civ. MeI
11
70%
ð10Þ
S C CH
C CHSCH2
i. BunLi, THF
ii. Se, 0 °Ciii. CSe2,
n
12
( )S Se
SeSe
S
Se
SeSe
CH2n
( )51–58%
ð11Þ
The lithium intermediate in this reaction can also be trapped by the addition of an alkyl isothio-cyanate introducing a sulfur substituent on the diselenole-2-selone ring (Equations (12) and (13))<2001AG(E)1122, 2001JMAC1026, 2002JOC4218>. This lithium intermediate can also be generatedby metallation of 1,2-dichlorovinylmethyl sulfide <2003JOC5217>. The potential versatility of thesemethods has been shown with the use of the acetylenic silane in this transformation (Scheme 8)<2000EJO3013>.
Se
SeSe
S
SMe
OMe
OC CHSMe
i, ii, iii
73%
i. BunLi, –78 °C, THF; ii. Se; iii. CSe2; iv. MeO2CCH2CH2SCN
ð12Þ
Se
SS
S
SSe
PhCOSe
PhCOSeS
SSe
Se
SeZn
2
i–iv v
i. LDA / THF, –78 °C, 2 h; ii. Se, –78 °C 1 h, rt, 2 h; iii. ZnCl2, MeOH, NH3;iv. Bu4NBr, MeOH; v. PhCOCl, acetone
10
(Bu4N)232% 61%
Scheme 7
578 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group
HC CS
OTHPSe
SeSe
SR
SOTHPi–iv
71–73%
i. BunLi, TMEDA, –70 °Cii. Se, 0 °Ciii. CSe2, –90 °Civ. RSCN
ð13Þ
Reactions of iminium salts with hydrogen selenide are widely used in the preparation oftriselenocarbonates. This route has been used for the preparation of triselenocarbonates contain-ing a 13C labeled selenocarbonyl group (Scheme 9) <2001MI1035>.
Electrochemical reduction of carbon diselenide provides a convenient route to the diselenium-substituted diselenol-2-selone (Scheme 10) <2001S1614>.
Se
SeSe
S
SiMe3
OMe
OC CHMe3Si
Se
SeSe
SiMe3
Se
SeSe
S OMe
O
Se
SeSe
i. BunLi, –78 °C, THF; ii. Se, 0 °C
iii. CSe2, –90 °C, MeO2CCH2CH2SCN
i, ii, iii
(Bun)4NF
66%
+
+
Scheme 8
NSe
Se
O Se
SeN+ Se
SeSe
PF6–
***
i. H2SO4; ii. HPF6; iii. H2Se, EtOH
i, ii iii
86% 53%
* denotes 13C
Scheme 9
Se
Se SeSe
Se
–Se
–Se
Se
Se CSe2 Se
SeSe
Se–
Se–
Se
SeSe
Se
SeZn
SeSe CO2Me
CO2MeSe
SeSe
Br(CH2)2CO2Me
2 CSe22 e–
–CSe–2
2 e–
Bun4NBr, ZnCl2
2
(Bun4 N)2
82%
82%
3
Scheme 10
Functions Containing a Selenocarbonyl or Tellurocarbonyl Group 579
Cyclooctyne reacts with carbon diselenide in the presence of selenium to afford the correspond-ing triselenocarbonate 13 (Equation (14)) <2000JOC8940>.
Se
SeSe+ CSe2 + Se
CH2Cl2, reflux
59%
13
ð14Þ
6.19.3.4 Selenocarbonyl Functions Flanked by Two Different Chalcogen Atoms RX(C¼Se)Y
Compounds with the selenocarbonyl group attached to two different chalcogen atoms have untilthe late 1990s been relatively rare <1995COFGT(6)587>. Increased interest in mixed fulvalenederivatives has led to novel approaches for the preparation of these compounds. The above-mentioned metallation route to diselenole-2-selones (Section 6.19.3.3, Equations (10)–(13)) can bereadily applied to the preparation of the corresponding sulfur–selenium heterocycles. Treatmentof the protected lithiated acetylene with sulfur followed by carbon diselenide and selenium andtrapping with ethyl iodide affords the desired selenocarbonate 14 (Equation (15)<2002JOC4218>. This method was also used for the preparation of novel 1,3-selenatellurole-2-selones such as 15 (Equation (16)) <1997CC1925, 2001PS(171–172)231>. Extension of thisreaction to other substituted acetylenic precursors and trapping with various electrophiles shouldmake this method a very versatile route to the mixed chalcogen-substituted selones.
HC CS
OTHPSe
SSe
SeEt
SOTHPi–iv
73%
i. BunLi, TMEDA, –70 °Cii. S, 0 °Ciii. CSe2, –90 °Civ. Se, EtI, 0 °C
14 ð15Þ
i. BunLi; ii. Te; iii. CSe2; iv. H2O
C CHMe3SiSe
TeSe
i–iv
83%
15ð16Þ
Another interesting metallation route affords the mixed sulfur–selenium heterocyclic seleno-carbonate 16 via an iminium salt intermediate (Scheme 11) <1998JMAC1945>. A similarreaction of an iminium salt with hydrogen selenide affording a related selenocarbonate has alsobeen reported <1992ZN(B)898>.
O
O
O
O Li
O
O Se NO
S
O
O
S
SeN O+
O
O
S
SeSe
Br –
i ii, iii
iv, v
vi
i. BuLi (1 equiv.), 0 °C; ii. Se, THF, –35 °C; iii. morpholino-4-thiocarbonylchloride, –78 °C; iv. Br2, CH2Cl2; v. 110 °C; vi. Se, NaBH4, AcOH–EtOH
68%
11%
16
Scheme 11
580 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group
6.19.3.5 Selenocarbamates RO(C¼Se)NHR, RS(C¼Se)NHR, RSe(C¼Se)NHR,RTe(C¼Se)NHR
A variety of methods have been described for the preparation of selenocarbonyl derivatives ofurethanes <1995COFGT(6)587>. Since 1995 there has been significantly increased interest indeveloping new synthetic methods in this area. Treatment of N,N-dimethylselenocarbamoyl chlor-ide (Section 6.19.2.2) with readily prepared lithium thiolates and selenolates provides a conve-nient route to N,N-dimethylamino-substituted thioseleno- and diselenocarbamates (Scheme 12)<2002JOC1008>. The use of other substituted selenocarbamoyl chlorides should make this a veryuseful general method for the preparation of other interesting selenocarbamate derivatives.
A general synthesis of O-alkylselenocarbamates involves a convenient one-pot procedure for thepreparation of the key intermediate isoselenocyanates <1994T639> (Scheme 13). The reactionsoccur in high yield and can be used for the preparation of O-alkylselenocarbamates derived fromprimary, secondary, and tertiary alcohols. The reaction also proceeds in an intramolecular mannerto afford the cyclic selenocarbamate 17 (Equation (17) <1997PS(120–121)335>.
Se HN O
Se
NC
OH
+80%
Et3N, THF
17
ð17Þ
The first report of the preparation of selenotellurocarbamic esters has appeared<1996OM5753>. Treatment of an acylisoselenocyanate with excess alkyl tellurol affords theselenocarbonyl Te-alkyl urethane 18 in yields of 20–40% (Equation (18)).
N C Se
O
NH
O
TeR
SeTHF
+ RTeH
–80 °C 20–42% 18
ð18Þ
Me2N C ClSe
Me2N CCl2 Cl–LiAlHSeH, 0 °C
RSeLi RSLi
Me2N C SeRSe
R = aryl, alkyl
51–95%
Me2N C SRSe
R = aryl, alkyl
66–74%
+
Scheme 12
RNH2 C HNH
OR
C Hi. EtOO
R N C R N C Se
C NH
R1OSe
R
i
, reflux, 12 h
ii iii
R = alkyl, aryl
R1OK
ii. Ph3P, Et3N, CCl4, 70 °C; iii. Se, Et3N
Scheme 13
Functions Containing a Selenocarbonyl or Tellurocarbonyl Group 581
An aryl selenocarbamate prepared from the aryl isoselenocyanate is an intermediate in the‘‘dehydration’’ of the very sensitive �-amino acid 19 <2003BMCL433> (Equation (19)).
CO2EtN
OH
Ht-BOC
N
NO2
C Se
CO2EtNHt-BOC
ii. H2O2
, Bun3P
90%19
i.
ð19Þ
Chiral oxazolidine-2-selones have proved to be useful as derivatizing agents for nuclear magneticresonance (NMR) determination of chirality due to the extraordinary sensitivity of the77Se chemical shift to the chemical environment. Details of the preparation of a variety of thesecompounds by directed metallation of readily available 2-oxazolines have been reported<1994JOC4977>. (4S,5R)-4-methyl-5-phenyl-oxazolidin-2-selone 20 has proved to be particularlyuseful for determination of chirality <1994TA1627, 1995TA833, 1995JOC5540, 1996CC1125,2002TA835>. The rapid reaction of this compound with an acid chloride or with an acid in thepresence of a coupling reagent affords chiral oxazolidine-2-selones suitable for NMR analysis(Scheme 14) <1994TA1627, 1994TL1329, 1999JA10478>.
Interesting ‘‘non-Evans’’ stereoselectivity has also been noted in aldol reactions of the readilyprepared N-acyl oxazolidine-2-selones 21 (Scheme 15) <2000JA386>. This stereoselectivity andthe above-mentioned sensitivity of the Se chemical shift to remote stereochemical centers in thisheterocyclic system have been explained by unusual C�H Se¼C interactions which have beendetected spectroscopically <2000AG(E)3067>.
A convenient conversion of the thiocarbonyl group of a thiocarbamate to the correspondingselenocarbonyl moiety involves treatment of the thiocarbonyl compound with triethyl orthoformateand boron trifluoride etherate followed by addition of sodium hydrogen selenide (Equations (20)–(22))<1995JA8528, 1998S1442, 2002TL3879, 2002JCS(P1)1568> (cf. Section 6.19.3.2, Scheme 4).
N O
PhMe
ii. Se
i. LHMDS
iii. Citric acid
ii. DCC, DMAP
HN C CO2H
CH3
Hi. BOC
*
HN O
PhMe
Se
N O
PhMe
SeO
NH
H3C
H
BOCi, ii
*
20
Scheme 14
N O
SeO
R3
R2
OH
R1
N O
R1
R3
R2
OH
OH
R1
i. LiHMDS, –78 °C; ii. Se; iii. R1CH2COCl;
iv. R3CHO-TiCl4; v. LiBH4
i–iii iv
v 98%1
R
iv
21
N
SeO
R1R2
O
Scheme 15
582 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group
S
NS
R2
R2
R1
S
NSe
R2
R2
R179–96%
R1 = Me, Ph
R2 = CO2Me, CN
i. ii. NaHSe, EtOH
BF3-ether, HC(OEt)3, CHCl3
ð20Þ
S
NS
R
Me
EtO2C
S
NSe
R
Me
EtO2C
ii. NaSeH, EtOH, rt
R = CH3, CH2CO2Et
i. BF3–ether, HC(OEt)3 reflux
ð21Þ
Se
Me
NS
Se
Me
NSe
ii. NaSeH, EtOH, rt
95%
i. BF3–ether, HC(OEt)3 refluxð22Þ
Alkylation followed by hydrogen selenide treatment also provides a route to selenocarbamates fromthe corresponding thiocarbonyl compounds (Equation (23)) <1996PJC1124, 1999ACS861>. Thealkylation–hydrogen selenide procedure can also be carried out starting from imines<1999PJC1315>.
yields 18–78%
R1 = alkyl, R2
= Ph, PhCH=CH
N
S
O
S
R1R2 N
S
O
Se
R1R2 i. Me2SO4
ii. H2Se ð23Þ
Treatment of methyl thiocyanate with HCl affords the iminium salt which upon treatment withlithium aluminum hydrogen selenide affords the corresponding thioselenocarbamate(Equation (24)) <2001TL6333>.
S CCH3 N S C NH2
SeCH3
i. HCl, THF, 0 °C
ii. LiAlHSeH
51%
ð24Þ
Bis(N,N-dialkylselenocarbamoyl)triselenides 22 can be prepared by reaction of chloroform (orsodium trichloroacetate) with secondary amines and elemental selenium in hexamethylphosphor-amide (HMPA) in the presence of sodium hydride (Equation (25)) <1994CL2105,1996BCJ2235>. Tetra-substituted selenoureas are also formed in this reaction, but the amountsof selenoureas formed can be controlled by temperature and the number of equivalents of amineused (cf. Section 6.19.4.1, Equation (28)).
Et2NH Se Et2N SeSe
Se NEt2
Se Se
+NaH, CHCl3, rt
46%22
ð25Þ
N,N-Dimethylformamide dimethylacetal reacts with elemental selenium to give a mixture of methylN,N-dimethylselenocarbamate and the isomeric Se-methyl carbamate (Equation (26))<1996JPR403>.
(MeO)2CHNMe2 + Se Me2N Se
O
MeMe2N O
Se
Me +
22% 33%
Xylene, refluxð26Þ
Functions Containing a Selenocarbonyl or Tellurocarbonyl Group 583
6.19.4 FUNCTIONS CONTAINING AT LEAST ONE NITROGEN FUNCTION(AND NO HALOGEN OR CHALCOGEN FUNCTIONS)
6.19.4.1 Selenoureas (R2N)2C¼Se
Selenoureas remain the most widely documented selenocarbonyl compounds. Thioureas can beconverted to selenoureas by alkylation followed by careful displacement using sodium hydrogenselenide. Reactions of isoselenocyanates with amines, addition of hydrogen selenide to carbodi-imides, and displacements of activated vinyl halides by selenourea also provide convenient generalroutes to selenoureas <1995COFGT(6)587>.
Reactions of isoselenocyanates with amines continue to provide one of the most convenientroutes to selenoureas (Equation (27)) <1997JIC161>.
NC
Se
H2NCH2R
HN C N
H
SeCH2R
+80–92%
ð27Þ
Treatment of N,N-dimethylselenocarbamoyl chloride (Section 6.19.2.2) with secondary orprimary amines proves a convenient route to N,N-dimethylamino-substituted selenoureas. Exten-sion of this method to the preparation of other N,N-disubstituted selenocarbamoyl chloridesshould make this a very useful general method for the preparation of di-, tri-, and tetrasubstitutedselenoureas (Equation (28)) <2002JOC1008>.
N HR1
RMe2N C Cl
Se
Me2N C NSe R1
R
rt
R, R1 = alkyl, 75–95%
R1 = alkyl, R = H, 27–55%
ð28Þ
N,N-Disubstituted selenoureas can be prepared in very good yields by treatment of N,N-dialkylaminocyanamides with HCl followed by treatment with lithium aluminum dihydrogenselenide (Scheme 16) <2001TL6333>. They can also be prepared by the direct reaction ofthe corresponding cyanamides with highly toxic gaseous hydrogen selenide generated fromaluminum selenide in the presence of sulfuric acid <1999PS(152)169>.
N,N0-Disubstituted selenoureas can be similarly prepared from the corresponding carbodii-mides by reaction with hydrogen chloride followed by treatment with lithium aluminum dihydro-gen selenide (Scheme 17) <2002SC3075>. This procedure avoids many of the problemsassociated with direct addition of hydrogen selenide.
Reactions of primary or secondary amines with triethyl orthoformate and selenium at elevatedtemperatures in a sealed vessel directly affords the corresponding selenoureas (Equation (29))<2003TL1295>. Both cyclic and acyclic selenoureas can be prepared using this method.
N C NR1
RN C
R1
RNH2
ClCl– N C
R1
RNH2
SeLiAlHSeHHCl, THF, 0 °C
70–91%
+
Scheme 16
i. HCl, rt, 4 h; ii. LiAlHSeH, 0 °C, 2 h
NR'CRN NR'CCl
RHN CRHNSe
NHR'i ii
56–93%
Scheme 17
584 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group
NH
NHR
R
(EtO)3CHN
NR
R
Se+i
39–95%
i. Se, 180–190 °, 8 h, sealed vessel
R = Me, Et, But
ð29Þ
Simple tetra-substituted selenoureas can be prepared by reaction of sodium trichloroacetate (orchloroform) with secondary amines and elemental selenium in HMPA in the presence of sodiumhydride (Equation (30)) <1994CL2105, 1996BCJ2235>. Bis-(N,N-dialkylselenocarbamoyl) tri-selenides are also formed in the reaction, but the amount of these formed can be controlled by varyingthe temperature and the amount of amine used in the reaction (cf. Section 6.19.3.5, Equation (25)).
Se SeN R1
R2NR1
R2
+ +NaH, HMPA
20–65%Cl3CCO2Na R1R2NH
R1, R2 = –(CH2)5–
R1, R2 = Et
R1, R2 = Bun
ð30Þ
Since 1994, three selenating agents have been used for the preparation of simple acyclic selenoureas.Bis-trimethylsilylselenide reacts with N,N,N0,N0-tetramethylurea in the presence of boron trifluorideetherate to afford the corresponding selenourea in good yield (Equation (31)) <1994BCJ876>.Monoselenophosphate reacts with cyanoguanidine to afford the corresponding selenocarbonyl com-pound in excellent yield (Equation (32)) <2001S1308>. A selenium analog of the widely used sulfur-based Lawesson reagent converts N,N0-diethylurea to the corresponding selenourea in modest yield,however, the reaction was not successful in the case of N,N0-diphenylurea <2001T5949>.
Me2N NMe2
O
Me2N NMe2
Se (Me3Si)2Se,
BF3·OEt2
64%
ð31Þ
C NNH
C
NHH2N N
HC CN
H2NSe
NH2
H HMeOH, H2O, H2PO3Se–
94%
H2PO4–
ð32Þ
Hydroxyimidoyl chlorides can be converted to selenoureas in moderate yield via intermediatenitrile oxides 23 and isoselenocyanate intermediates (Scheme 18) <1999JOC6473>.
Cl
N
CH3
OH
C
CH3
N O–
N
CH3
C Se
CH3
HN
HN
R1
Se
R NH2
Se
R1NH2
46–78%
i
i. Et3N, THF, 25 °C; ii. 0 °C, THF, ii
23
Scheme 18
Functions Containing a Selenocarbonyl or Tellurocarbonyl Group 585
A number of aromatic acyl selenoureidonitriles and esters have been prepared by reaction ofthe corresponding amines with an acyl isoselenocyanate (Equation (33)) <1997MI135,1999CCC1673>. These compounds can be readily cyclized to the corresponding fused selenium-containing heterocycles <2000MI37>.
S
R
NH2 NAr
O
C Se S
R
NH
C NH
C ArSe O+
R = CN, CO2Et
72–96% ð33Þ
Reactions of in situ-generated acyl isoselenocyanates with aniline derivatives affordN-acyl-selenoureas in good yield (Scheme 19) <1994MI42>. Aliphatic amines react similarly<2000HCA539>. Related reactions also occur with N-phenylimidoyl isoselenocyanates (Scheme20) <2000HCA1576> and N-benzylbenzimidoyl isoselenocyanates <2002HCA1102>. Primaryamines can also be used in the latter reactions, but significantly lower yields were obtained usingammonia.
Reaction of isonitriles with amines in the presence of 1,5-diazabicyclo[5.4.0]undec-5-ene (DBU)provides a convenient preparation of selenoureas, which can be readily converted by oxygen tothe corresponding carbodiimides (Equation (34)) <1999SL75>.
R1NH2 NH
CNH
SeRR N C– N C NR1
iii
i. Se, DBU, reflux, 1 h; ii. O2, reflux
R+
R1
ð34Þ
Similarly 75Se-labeled dicyclohexylselenourea has been prepared in 90% radiochemical yield bythe reaction of cyclohexylisonitrile and cyclohexylamine in the presence of 75Se (Equation (35))<2001MI140>. Labeled dicyclohexylselenourea can also be prepared directly by addition of labeledhydrogen selenide to the corresponding carbodiimide <2001MI578> (Scheme 21). The resultinglabeled selenourea is a useful precursor in the preparation of 75Se-labeled selenides. A polymer-bound selenourea could also be prepared from the corresponding carbodiimide (Equation (36)).
Ar C ClO
KSeCN N C SeCArO
NHAr'NHCArO
SeAcetone Ar'NH2
71–83%
Scheme 19
i. KSeCN, acetone
R = alkyl, aryl, H
Ar NH
PhO SOCl2
Ar Cl
NPh
Ar N
NPh
C SeAr N
HNPh
R2N Se
i >98%
74–97%
R2NH
Scheme 20
586 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group
NH
NH
75SeNC NH2
+
Benzene, reflux
90% radiochemical yield
75Sen ð35Þ
NH
NH
75Se
N C N H275Se+ ð36Þ
A novel approach to the preparation of heterocyclic selenoureas involves direct reaction ofstabilized cyclic carbenes with elemental selenium. The intermediate carbene 24 can be preparedby reaction of 2,20-bipyridine with a triphenylarsonium salt, followed by bromide exchange andbase treatment. The resulting carbene is stable for several hours at �30 �C, but can be trapped byelemental selenium affording the selenourea in high yield (Scheme 22). This selenourea can bedirectly prepared in 87% yield in a ‘‘one-pot’’ reaction without isolation of the carbene<1998AG(E)344, 2000EJIC1935>. The reaction of other stabilized carbenes with selenium alsoafford selenoureas (Equation (37)) <1996LA2019>.
N
N
N
Ph
Ph
Ph
N
N
N
Ph
Ph
PhSe
Se, toluene, refluxð37Þ
NH
NH
75Se
N C N H275Se
i.Br CO2Et
NHBOC
Me75Se NHBOC
CO2Et
+
i, ii, iii
ii. Bun4N+ –OH
iii. MeI
Scheme 21
N NPh3As OTf
NN
HH 2OTf
–OTf
NN
H Br
NNNN
Se
Se
+
–Ph3As
CH3CN, reflux
KOtBu, –30 °C, THF
87%
24
Bu4NBr+
+++
Scheme 22
Functions Containing a Selenocarbonyl or Tellurocarbonyl Group 587
Reaction of a series of electron-rich tetraalkylaminoethylenes with elemental selenium atelevated temperature affords the corresponding selenoureas in excellent yields, presumably viaintermediate stable carbenes (Equation (38)) <1996AF1154>.
N
NMe
MeN
NMe
MeN
NMe
Me
Se
Se,
96%
toluene, refluxð38Þ
6.19.4.2 Other Cyclic N(C¼Se)N Compounds
Traditional methods for the preparation of selenopyrimidines and selenopurines using selenourea con-tinue to prove useful in the preparation of novel selenium analogs of biologically important compounds.Condensation of selenourea with ethyl 3-keto-hexanoate afforded propylselenouracil 25 the seleniumanalog of thewidely used antithyroid drug 6-propyl-2-thiouracil (PTU) (Equation (39))<1994OPP682>.
OEt
O O
H2N NH2
Se
NH
HN Se
O
+ KOH, H2O
25
ð39Þ
The 2- and 4-selenopyrimidine nucleosides have also been prepared via displacement reactionsusing selenourea and sodium hydrogen selenide (Schemes 23 and 24) <1999MI635>. Detailsof the introduction of selenium into selenoguanosine derivatives using selenourea have also beenreported <1994JMC3561>.
O
XRO
N NHRO
O
O
O
XRO
N NRO
O
Cl
O
XRO
N NHRO
Se
O
i ii
i. SOCl2, DMF, CHCl3; ii. (NH2)2C=Se or NaHSe, MeOH or EtOH, 90 °C, N2
a. R = Bz, X = OBzb. R = p -Tol, X = H
a. R = Bz, X = OBzb. R = p -Tol, X = H
a. R = H, X = OHb. R = H, X = H
Scheme 23
90 °C, N2
O
OBzBzO
N NBzO
Se
NH2
F
NH
HN
O
O
F
N
NF
Cl
Cl N
NF
NH2
Cl NH
NF
NH2
Se
O
OHHO
N NHO
Se
NH2
F
iii iii
iv
v
i. POCl3; ii. aq. NH3, iii. NaHSe, n -BuOH, Ar;iv. BSTFA, MeCN, SnCl4, rt, 2 h; v. NH3, MeOH
Scheme 24
588 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group
The 2-selenoxoquinazoline derivative 26 can be conveniently prepared via cyclization of2-isoselenocyanatobenzonitrile using hydrazine hydrate (Scheme 25) <1995PHA21>.
The reaction of 5-aminoimidazole-4-carbonitrile with n-butylisoselenocyanate affords 27. Reac-tion with benzhydrylisoselenocyanate takes a very different course yielding the 1-selenopurine 28(Scheme 26) <1995H47>.
Acyl selenoureidocarbonitrile 29, readily prepared by reaction of the corresponding nitrile withan acyl isoselenocyanate (Section 6.19.4.1, Equation (33)) can be readily cyclized to the corre-sponding fused selenopyrimidine 30 (Equation (40)) <1999CCC1673>. It is interesting that veryslight structural changes can lead to the tautomeric selenol form 31 being observed as theexclusive product of this reaction (Equation (41)).
N
NH
S Se
NH2
S
CN
NH
C NH
C PhSe O
KOH, MeOH, heat
29 30
ð40Þ
S
N
NSeH
H2N
S
CN
NH
C NH
C PhSe O
KOH, MeOH, heat
31
ð41Þ
The reaction of the aryl isoselenocyanate with the heterocyclic thiourea provides a convenientroute to a number of interesting heterocyclic selenoureas, including the hypervalent sulfur-containing selone 32 and -diselone 33 (Scheme 27) <2002JHC189>.
CN
N C Se
CN
N CCl2 NH
N
NH
Se
NH2NH2NH2,
H2O
81% 72%
NaHSe, Na2CO3
26
Scheme 25
NH
N
NH
NBun
Se
NH
H2N
NC
NH
N
N
Se
NH
N
NH
Ph
Ph
NH Ph
Ph
Se
N C SePh
Ph
N C SeBun
50 °C, 16 h
50 °C, 16 h
27
28
Scheme 26
Functions Containing a Selenocarbonyl or Tellurocarbonyl Group 589
6.19.4.3 Telluroureas (R2N)2C¼Te
A series of stable cyclic telluroureas have been conveniently prepared in excellent yields by thereaction of the stable carbene imidazol-2-ylidenes 34 with elemental tellurium (Equation (42))<1993CB2047, 1997JA12742>. The special stability of the 2-telluroimidazolines is probably dueto the major resonance contributor 35.
N
NR1
R1
R
R
Te
N
NR1
R1
R
R
Te+THF, 0 °C
R, R1 = Me
R = Et, R1 = Me
R = Pri, R1 = Me
R = Mes, R1 = H
R = Mes, R1 = Cl
90–100%
34 ð42Þ
N
NR1
R1
R
R
TeN
NR1
R1
R
R
Te–+
35
Reactions of electron-rich tetraaminoethylenes with tellurium also afford telluroureas(Equation (43)) <1996AF1154>. It is likely that this reaction and previously described prepara-tions of telluroureas <1995COFGT(6)587> which required relatively vigorous conditions alsoproceeded via similar carbene intermediates.
N
NMe
MeN
NMe
MeN
NMe
Me
TeTe
88%toluene, reflux
ð43Þ
Another stable carbene approach to telluroureas parallels the previously described carbene routeto selenoureas (cf. Section 6.9.4.1, Scheme 22). Treatment of the bromide salt 36 with base in thepresence of tellurium affords the tellurourea in 87% yield (Equation (44)) <2000EJI1935>.
N C SeArN N
SN
S
Me
N N
SNN
SeS
ArMe
N N
SN
Se
Ar
N C SeAr
N C Se–Ar
N N
SNN
SeSe
ArAr
95%
170 °C –MeNCS91%
170 °C
59%
Ar = 4-CH3OC6H4 32
33
+
Scheme 27
590 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group
NN
H Br–
NN NN
Te
TeKOtBu, THF
87%
36
–30 °C+ ð44Þ
Up to the year 2003, no acyclic telluroureas have been reported in the literature.
6.19.5 HYPERVALENT SELENOCARBONYL COMPOUNDS OF THE TYPE Se¼C(X)X0
The reaction of 1,3-dimethyl-4-imidazolin-2-selone with molecular iodine affords a stable hypervalentselenocarbonyl compound 1,3-dimethyl-4-imidazolin-2-ylium diiodoselanide 37 characterized by alinear I�Se�I arrangement of atoms (Equation (45)) <1994G445>. A similar linear Br�Se�Brarrangement was noted when the same imidazolin-selone was treated with bromine <1998EJI137>.When the 1,10-bis(3-methyl-4-imidazolin-2-selone)methane 38 was treated with iodine a linearI�I�Se structure (39) was observed <1994G445> in contrast to linear Br�Se�Br structures notedfor other bis-halo adducts with other selenoureas (Equation (46)) <1998EJI137>.
N
N
Me
Me
Se X2
CH2Cl2 N
N
Me
Me
SeX
X
+
X = I, Br37
ð45Þ
NNMe
SeI
NN
Se I II
MeNNMe
Se
NN
Se
Me
I2
CH2Cl2
38 39
ð46Þ
Hypervalent adducts of N-methylbenzothiazole-2-selone and related compounds show a fasci-nating variety of structural types <1999JCS(D)2219>. A ‘‘T-shaped’’ structure was noted fordibromide 40 <1999JCS(D)2845>. Aryltellurium halide adducts 41 and 42 of the same benzothia-zole precursor have also been reported <1996ACS759, 2002PS(177)853>. Spectroscopic evidencefor 1:1 selenocarbonyl–Cl2 adducts has also been reported <1999JCS(D)4245>.
N
S
Me
Se
Br
Br
N
S
Me
Se
Te
Br
Ph
N
S
Me
Se Te
Cl3
OCH3
40 41 42
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1026–1033.2001MI140 T. Blum, J. Ermert, H. H. Coenen, J. Labelled Cpd. Radiopharm. 2001, 44, S140–S142.2001MI587 T. Blum, J. Ermert, H. H. Coenen, J. Labelled Cpd Radiopharm. 2001, 44, 587–601.2001MI1035 J. B. Christensen, K. Bechgaard, G. Paquignon, J. Labelled Cpd Radiopharm. 2001, 44, 1035–1041.2001PS(171–172)231 T. Otsubo, K. Takimaya, Y. Aso, Phosphorus Sulfur Silicon 2001, 171–172, 231–253.2001S1308 R. Kaminski, R. S. Glass, A. Skrowronska, Synthesis 2001, 1308–1310.2001S1614 M. Kodani, K. Takimiya, Y. Aso, T. Otsubo, T. Nakayashiki, Y. Misaki, Synthesis 2001, 1614–1618.2001T5949 P. Bhattacharyya, J. D. Woollins, Tetrahedron 2001, 42, 5949–5951.2001TL6333 M. Koketsu, Y. Fukuta, H. Ishihara, Tetrahedron Lett. 2001, 6333–6335.2002HCA1102 P. K. Atanassov, Y. Zhou, A. Linden, H. Heimgartner, Helv. Chim. Acta 2002, 85, 1102–1117.2002JCS(PI)1568 Z. Casar, I. Leban, A. Majcen-Le Marechal, D. Lorcy, J. Chem. Soc., Perkin Trans. 1 2002, 13,
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4218–4227.2002PS(177)853 G. K. Quinn, M. D. Rudd, J. A. Kautz, Phosphorus Sulfur Silicon 2002, 177, 853–862.2002SC3075 M. Koketsu, N. Takakura, H. Ishihara, Synth. Commun. 2002, 31, 3075–3079.2002TA835 E. Hedenstrom, B. V. Nguyen, L. A. Silks, Tetrahedron Asymmetry 2002, 13, 835–844.2002TL3879 R. Toplak, P. Bernard-Rocherulle, D. Lorcy, Tetrahedron Lett. 2002, 43, 3879–3882.2003BMCL433 J. Mittendorf, F. Kunisch, M. Matzke, H. Militzer, A. Schmidt, W. Schonfeld, Biorg. Med. Chem.
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Functions Containing a Selenocarbonyl or Tellurocarbonyl Group 593
Biographical sketch
Lynn James Guziec was born in Long Beach,California; she studied at Russell Sage Col-lege, Troy, NY where she received her B.A.,special honors in Chemistry, in 1979. Shereceived her Ph.D. in 1988 from New MexicoState University under the direction of FrankGuziec, Jr. She remained as a College Profes-sor at New Mexico State University until1995. She has been working as an AssistantProfessor at Southwestern University since1996. In 1998 she received an M.Sc. in Biolo-gical Sciences from the University of War-wick, UK. Her interests include heterocycles,organosulfur and organoselenium com-pounds, as well as the synthesis of medicinaland anticancer compounds.
Frank Guziec was born in Chicago, he studiedat Loyola University of Chicago where hereceived a B.S. (Honors) degree in 1968. Hereceived his Ph.D. degree in 1972 at MITunder the direction of Professor J. C. Sheehan.He carried out postdoctoral work atImperial College, London with ProfessorD. H. R. Barton, at MIT with H. G. Khorana,and at Wesleyan University with M. Tishler.He has served on the Chemistry faculties ofTufts University, New Mexico State Univer-sity and is currently Dishman Professor ofScience at Southwestern University. He car-ried out sabbatical research in the Pharmaceu-tical Sciences Department at DeMontfortUniversity, Leicester, UK with L. Pattersonunder a Fulbright Fellowship and withH. Hiemstra at the University of Amsterdam.His scientific interests include the chemistry oforganoselenium compounds, extrusion reac-tions, functionalizing deamination reactions,and sterically hindered molecules. Collaborat-ing with his wife Lynn Guziec he is alsoinvolved in the design and synthesis of anti-cancer compounds.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 573–594
594 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group
6.20
Functions Containing an
Iminocarbonyl Group and at Least
One Halogen; Also One Chalcogen
and No Halogen
T. L. GILCHRIST
University of Liverpool, Liverpool, UK
6.20.1 INTRODUCTION 5956.20.2 FUNCTIONS CONTAINING AT LEAST ONE HALOGEN 5966.20.2.1 Iminocarbonyl Compounds with Two Similar Halogen Functions 5966.20.2.1.1 Carbonimidic difluorides, F2C¼NR 5966.20.2.1.2 Carbonimidic dichlorides, Cl2C¼NR 5976.20.2.1.3 Carbonimidic dibromides, Br2C¼NR 597
6.20.2.2 Iminocarbonyl Compounds with Two Dissimilar Halogen Functions 5986.20.2.3 Iminocarbonyl Halides with One Halogen and One Other Heteroatom Function 5986.20.2.3.1 Iminocarbonyl chlorides with one other heteroatom function 598
6.20.3 FUNCTIONS CONTAINING AT LEAST ONE CHALCOGEN (AND NO HALOGENS) 5996.20.3.1 Iminocarbonyl Compounds with Two Similar Chalcogen Functions 5996.20.3.1.1 Iminocarbonyl compounds with two oxygen functions 5996.20.3.1.2 Iminocarbonyl compounds with two sulfur functions 5996.20.3.1.3 Iminocarbonyl compounds with two selenium functions 600
6.20.3.2 Iminocarbonyl Compounds with Two Dissimilar Chalcogen Functions 6006.20.3.2.1 Iminocarbonyl compounds with one oxygen and one sulfur function 6006.20.3.2.2 Iminocarbonyl compounds with one oxygen or sulfur and one selenium function 601
6.20.3.3 Iminocarbonyl Compounds with One Chalcogen and One Other Heteroatom Function 6016.20.3.3.1 Iminocarbonyl compounds with one oxygen and one nitrogen function 6016.20.3.3.2 Iminocarbonyl compounds with one sulfur and one nitrogen function 6026.20.3.3.3 Iminocarbonyl compounds with one selenium and one other heteroatom function 602
6.20.1 INTRODUCTION
This chapter covers methods of synthesis of a wide range of iminocarbonyl compounds that havetwo heteroatoms attached to the carbon of the iminocarbonyl function. Only a few new methodsfor the preparation of these compounds have been described since the earlier review (chapter 6.20in <1995COFGT(6)601>). The new methods, and new examples of the more important generalmethods, are described here.
595
6.20.2 FUNCTIONS CONTAINING AT LEAST ONE HALOGEN
6.20.2.1 Iminocarbonyl Compounds with Two Similar Halogen Functions
Compounds having the formula XYC¼NR (X,Y=halogen) are named as carbonimidic dihalidesunder the IUPAC nomenclature system. They are also commonly referred to as isocyanide dihalides oras iminocarbonyl dihalides in the literature. The most detailed review of methods of preparation ofcarbonimidic dihalides is by Kuhle<1983HOU(E4)522>. The majority of compounds of this type beartwo similar halogen functions. The most common compounds of this class are carbonimidic dichlorides(X,Y=Cl) and several have been found as natural products in marine organisms; these includeexamples that have been described since the publication of COFGT (1995) <1999JNP1339,2001JNP111, 2001JNP939>. The general methods available for compounds in this class remain thosedescribed in chapter 60.20.1.1 in<1995COFGT(6)601>; new examples of these methods and a few newspecific methods are described in the following sections. There are no new reports of methods fordihaloiminium cations or for carbonimidic diiodides.
6.20.2.1.1 Carbonimidic difluorides, F2C¼NR
Methods for the preparation of carboimidic difluorides are those described in chapter 60.20.1.1.1 in<1995COFGT(6)601>. The most general of these methods are summarized briefly in Scheme 1.Further examples of the conversion of carbonimidic dichlorides into carbonimidic difluorides(method B) have been described <2001JFC(109)123>. A further illustration of method D is thepreparation of perfluorinated carbonimidic difluorides by the dechlorination of the perhaloalkane 1with a catalytic amount of trimethyltin chloride (Equation (1)) <1995AG(E)586>.
N
F
F
N(CF3)2
N
F
F
N(CF3)2
Cl
Cl
Me3SnCl, 25 °C
1
Quant. ð1Þ
A new method for the preparation of N-(trifluoromethyl)carbonimidic difluoride 2 is the thermaldecomposition of potassium perflluorodimethylaminoacetate (Equation (2)); compound 2was obtainedas the principal product, but it was not completely separated from by-products <1999JFC(95)161>.
NF
F
CF3
NF
F
CF3
CF3
O2CK270–280 °C
2
45% ð2Þ
NR
Cl
Cl
NR
F
F
F
FF
NHR
NR
F
ClF
N(Cl)R
F
F2
A
B
C
D
KF or base
+
Scheme 1
596 Functions Containing an Iminocarbonyl Group and at Least One Halogen
6.20.2.1.2 Carbonimidic dichlorides, Cl2C¼NR
The most general methods for the preparation of carbonimidic dichlorides are summarized inScheme 2. All these methods were described in chapter 60.20.1.1.2 in <1995COFGT(6)601>. Afew publications that include some experimental detail have appeared with additional examples ofsome of these methods. Thus, some new N-arylcarbonimidic dichlorides have been prepared bythe reaction of aryl isothiocyanates with chlorine (method A) <1997SC2645>. A new exchangereaction has been used to prepare 2-biphenylylcarbonimidic dichloride from the correspondingdibromide (Equation (3)) <1995CC2295>.
N
Br
Br
PhN
Cl
Cl
PhSO2Cl2, SnCl4
ð3Þ
6.20.2.1.3 Carbonimidic dibromides, Br2C¼NR
The addition of bromine to isocyanides (Equation (4)) is the most general method for thepreparation of carbonimidic dibromides. A wide range of isocyanides has been used and severalnew examples have been reported <1995CC2295, 1996CC41, 1996S975>. The reaction can beused as a method of protection of sensitive isocyanide functions since it can be reversed byreduction with triethyl phosphite or magnesium <1996CC41, 1996S975>.
NR
Br
Br
NRBr2 + ð4Þ
The dibromooxime 3 has been prepared from glyoxylic acid aldoxime and bromine asdescribed in chapter 60.20.1.1.3 in <1995COFGT(6)601>. The oxime 3 is important as a sourceof the nitrile oxide 4, a useful 1,3-dipole (Scheme 3). The reaction sequence is oftencarried out without isolation of the intermediate dibromooxime 3 <1994T7543, 1995LA619> butthere is also a description of a further experimental procedure for its isolation <1997JHC345>.An analogous procedure has been used to generate carbonimidic dibromides (without
NR
Cl
Cl
NRSCl2
NRCl2 or SO2Cl2
A
B
C
D
NHRO
NClRCl
SO2Cl2, SOCl2
(R = aryl )
Scheme 2
N
Br
Br OH
N
OH
HO2CBr N O
3 4
+ –
Scheme 3
Functions Containing an Iminocarbonyl Group and at Least One Halogen 597
isolation) from the benzylhydrazone <1994T7543> and the phenylhydrazone <1999TL2605> ofglyoxylic acid.
6.20.2.2 Iminocarbonyl Compounds with Two Dissimilar Halogen Functions
No further advances in this area have occurred since the publication of chapter 6.20.1.2 in<1995COFGT(6)601>.
6.20.2.3 Iminocarbonyl Halides with One Halogen and One Other Heteroatom Function
There have been very few advances since the publication of chapter 6.20.1.3 in<1995COFGT(6)601>. The most general method of preparation of compounds of this type isthe selective displacement of one halogen from the appropriate iminocarbonyl dihalides, the maindifficulty being in limiting the displacement to a single halogen. Other approaches that have somegenerality are addition reactions to isocyano groups and (for chloro compounds) chlorination ofprecursors such as isothiocyanates, ureas, and thioureas. New examples of these reactions aremainly restricted to iminocarbonyl chlorides with a nitrogen function.
6.20.2.3.1 Iminocarbonyl chlorides with one other heteroatom function
The electrophilic addition of sulfenyl chlorides to isocyanides is a known method for the prepara-tion of iminocarbonyl chlorides with a sulfur function. A specific extension of this method to anitrogen species is the addition of N-chlorobenzotriazole to isocyanides, which leads to mixturesof N-1 substituted and N-2 substituted benzotriazoles 5 and 6 (Equation (5)) <2001JOC2854>.The method appears to have the potential of extension to other N-halo compounds.
NN
N
Cl
NR NN
N
Cl
NR
N NN
Cl
NR+ +
5 6
R = Ar, Bn, TsCH2, BtCH2
70–93%
ð5Þ
Carbonimidic chlorides that bear a nitrogen function have proved to be useful intermediatesin various heterocyclic syntheses. Two recent examples that represent applications of knownmethods are illustrated in Scheme 4. A synthesis of 2,4-diaminoquinazolines makes use of
O
Et2N
NH
X
PCl5
Cl
Et2N
N
X
N
N
NEt2
NMe2
X
N
NH2
CN
Cl
Cl
NMe2 Cl
N
N
CN
NMe2
Cl
N
N N
NMe2
Cl
7
Me2NCN, TiCl4
8 HCl (g)
9
Scheme 4
598 Functions Containing an Iminocarbonyl Group and at Least One Halogen
the imidoyl chlorides 7 as key intermediates; they are prepared from N-aryl-N0,N0-diethylureas byreaction with phosphorus pentachloride <1998H(48)319>. The reaction of primary amines withdichlorodimethyliminium chloride 8 is a known and efficient method for the preparation ofdimethylamino substituted imidoyl chlorides and this method has been used in a synthesis ofthe pyrrolotriazine 9 <1996T3037>.
6.20.3 FUNCTIONS CONTAINING AT LEAST ONE CHALCOGEN(AND NO HALOGENS)
6.20.3.1 Iminocarbonyl Compounds with Two Similar Chalcogen Functions
6.20.3.1.1 Iminocarbonyl compounds with two oxygen functions
A general method for the preparation of compounds of this class (carbonimidic diesters) is thedisplacement of chloride from carbonimidic dichlorides by an excess of an alcohol or a phenolunder basic conditions. A recent variation of this method that has been used to preparethe iminodioxolenes 10 is the cathodic reduction of diaryl-substituted 1,2-diketones in the presenceof N-arylcarbonimidic dichlorides (Equation (6)) <1994TL2365, 1995T3641>. Otherwise, themethods of preparation of these diesters are as described in chapter 6.20.2.1.1 in<1995COFGT(6)601>.
Cl
Cl
NAr 3
O
O
Ar1
Ar 2
O
ONAr 3
Ar1
Ar 2
+2e
10
ð6Þ
6.20.3.1.2 Iminocarbonyl compounds with two sulfur functions
Carbonimidic dithioesters are usually prepared most conveniently by S-alkylation of dithiocarba-mate salts or esters, which are in turn readily available from the reaction of primary aminocompounds with carbon disulfide. Methods involving displacement of halide are relatively lessused, but new examples of such reactions include routes to the sulfones 11 (R=Me or Ph) bydisplacement of bromide <1997JA5982, 1998CC1143>. The sulfur(II) substituent in compounds11 can be oxidized by MCPBA to give the bis(sulfones) 12 (Scheme 5). The oxime 14 wasprepared in high yield by a double displacement reaction of the sulfone functions of compound13 by sodium methylmercaptide (Equation (7)) <1997JA5982>.
O2S
SO2
NOBn
MeS
MeS
NOBn
13
92%
14
2 NaSMe
ð7Þ
NOTHP
PhO2S
Br
RSNaNOTHP
PhO2S
RS
MCPBANOTHP
PhO2S
RO2S78–85%
11 12
Scheme 5
Functions Containing an Iminocarbonyl Group and at Least One Halogen 599
6.20.3.1.3 Iminocarbonyl compounds with two selenium functions
There are no general methods for the preparation of this small class of compounds. An exampleof a preparation of an acyclic species from an isoselenocyanate is shown in Equation (8), butthis method has no generality <1996T12165>. Most of the known compounds of this class are2-iminodiselenoles; two examples of the preparation of these compounds are shown inScheme 6 <1996ZOR1870, 2000CEJ1153>.
ButSe
BuSe
N
Me
Me
MeN
Me
Me
MeSeButLi, BuI
31%ð8Þ
6.20.3.2 Iminocarbonyl Compounds with Two Dissimilar Chalcogen Functions
With the exceptions of the reactions detailed below the methods for the preparation of thesecompounds are as described in chapter 6.20.2.2 in <1995COFGT(6)601>.
6.20.3.2.1 Iminocarbonyl compounds with one oxygen and one sulfur function
Isothiocyanates are the most commonly used starting materials for the preparation of compoundsof this class; an alkoxide is added to the isothiocyanate to give a salt that is then S-alkylated.Some new examples of this method, with sodium methoxide as the nucleophile, have beendescribed <1995SC3973>. An example of the procedure in which tributyltin oxide is used asthe base is shown in Scheme 7 <1997H(45)1913>. The dithiazolone 15 has been prepared bya related method involving one-pot N-acylation and S-thiolation of ethyl thiocarbamate<1996JOC6639>.
SeN
NMeSe NPh
Se
SeMe
NPh
Se
SeMe
NMe2
MePF6
Se
SeMe
Me
I
NMe2
NH
ISe
SeMe
NNMe2
Me
+KOBut
53%
I2, NH4OH
90%
Scheme 6
S N
TMS
NH
TMSEtO
S EtOTfN
TMSEtO
EtS
NH2
S
EtOO
ClS
Cl
Et3N
N
SS
EtO
O
EtOH, (Bu3Sn)2O
74% 60%
+63%
15
Scheme 7
600 Functions Containing an Iminocarbonyl Group and at Least One Halogen
A new method for the preparation of 2-acetylimino-1,3-oxathiazoles is illustrated in Scheme 8.Reaction of the dicyano epoxide 16 with potassium thiocyanate and acetic anhydride gave theoxathioles 17; the five-membered ring is probably formed by intramolecular addition of a hydroxylgroup to the CN triple bond, as shown <1993JCS(P1)351>.
6.20.3.2.2 Iminocarbonyl compounds with one oxygen or sulfur and one selenium function
A few new compounds in this category have been prepared by methods analogous to those inthe two preceding sections. The first 1,3-oxaselenoles 18, having structures analogous tothe oxathioles 17 but with selenium in place of sulfur, were prepared by the method shownin Scheme 8 but with potassium selenocyanate as the nucleophile <1993JCS(P1)351>.2-Phenylimino-1.3-thiaselenole 19 has been prepared in low yield by a method analogous tothat in Scheme 6, from the reaction of phenyl isoselenocyanate with 1,2,3-thiadiazole(Equation (9)) <1996ZOR1870>. A displacement reaction analogous to that of Scheme 5has been carried out using the sodium salt of benzeneselenol (NaSePh) to give the sulfone 20<1998CC1143>.
SN
NSe NPh
S
SeNPh
N
OTHP
PhSe
PhO2SO
SeAr
NC
NAc
+KOBut
12%
18 20
19
ð9Þ
6.20.3.3 Iminocarbonyl Compounds with One Chalcogen and One Other Heteroatom Function
With the exceptions described below, the general methods available for compounds in this classremain those described in chapter 60.20.2.3 in <1995COFGT(6)601>.
6.20.3.3.1 Iminocarbonyl compounds with one oxygen and one nitrogen function
Compounds of this class are commonly known as isoureas or as pseudoureas. A review of theirmethods of preparation and their properties has appeared <1995RCR929>. General methodsfor their preparation include addition of nucleophiles to the CN triple bond of cyanates orcyanamides, and addition–elimination reactions of other iminocarbonyl compounds. Two newexamples of these two general approaches are shown below. The salt 21 was prepared fromcyanamide by reaction with butanol and anhydrous 4-toluenesulfonic acid in anhydrous chloroform(Equation (10)) <1999JA5940>. Displacement by an amine of one phenoxy group from theactivated iminocarbonate 22 gave the isourea 23 in good yield (Equation (11)) <2000HCA287>.
O
CNNC
Ar
SCN
NC CN
OH
SCNAr
O
SNH
NCNC
ArAc2O
O
SAr
NC
NAc42–69%
16 17
Scheme 8
Functions Containing an Iminocarbonyl Group and at Least One Halogen 601
NH2N H2
H2N
BuO
OTsBuOH, 4-TsOH anhyd.
70%
21
Nð10Þ
NCN
PhO
PhO
O2NO NH2.HNO3
Et3NNCN
HN
PhO
O2NO+87%
22 23
ð11Þ
6.20.3.3.2 Iminocarbonyl compounds with one sulfur and one nitrogen function
Compounds of this type are commonly known as isothioureas. This large and mostly stable groupof compounds can be prepared by a variety of methods, the most general of which is S-alkylationof thioureas. The thioureas can, in turn, be prepared by the addition of nitrogen nucleophiles toisothiocyanates. An example of this reaction sequence, through the intermediate thiourea 24followed by S-methylation, is shown in Scheme 9 <1997H(45)1405>.
Another method that is useful for isothioureas that bear an activating group on nitrogen isnucleophilic displacement from activated carbonimidic dithioesters. A new example of thismethod is the preparation of the iminothiazolidine ester 25 (Equation (12)) <2000SL33>.
NCN
MeS
MeS
HSNH2.HCl
CO2Et Et3NHN
SNCN
EtO2C
+95%
25
ð12Þ
6.20.3.3.3 Iminocarbonyl compounds with one selenium and one other heteroatom function
Compounds of this type are almost entirely restricted to those with a selenium and a nitrogenfunction, commonly known as isoselenoureas. As with isothioureas, the most general method forthe preparation of such compounds is Se-alkylation of selenoureas. An example of this approachthat has been used to prepare the selenazolone 26 is shown in Equation (13) <2002S195>.
N
Se O
N
NH2
Se
N
O
ClCl+
Pyr, 0 °C
29%
26
ð13Þ
S N
TMS
NH
NH
S
N
TMS
N
MeS
N
TMS
MeI
24
97% (2 steps)
Scheme 9
602 Functions Containing an Iminocarbonyl Group and at Least One Halogen
A related new approach to isoselenureas makes use of isocyanides as starting materials. Theaddition of a lithium dialkylamide and selenium to the isocyanide gave the lithium salts 27 whichwere then converted into isoselenoureas 28 by Se-alkylation with iodobutane (Scheme 10)<1997T12159>.
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12159–12166.1998CC1143 S. Kim, J. H. Cheong, Chem. Commun. 1998, 1143–1144.1998H(48)319 W. Zielinski, A. Kudelko, E. M. Holt, Heterocycles 1998, 48, 319–328.1999JA5940 R. A. Moss, L. A. Johnson, D. C. Merrer, G. E. Lee, J. Am. Chem. Soc. 1999, 121, 5940–5944.1999JFC(95)161 M. Nishida, H. Fukaya, E. Hayashi, T. Abe, J. Fluorine Chem. 1999, 95, 161–165.1999JNP1339 J. Tanaka, T. Higa, J. Nat. Prod. 1999, 62, 1339–1340.1999TL2605 F. Foti, G. Grassi, F. Risitano, Tetrahedron Lett. 1999, 40, 2605–2606.2000CEJ1153 A. Chesney, M. R. Bryce, S. Yoshida, I. F. Perepichka, Chem., Eur. J. 2000, 6, 1153–1159.2000HCA287 M. Bertinaria, G. Sorba, C. Medana, C. Cena, M. Adami, G. Morini, C. Pozzoli, G. Coruzzi,
A. Gasco, Helv. Chim. Acta 2000, 83, 287–299.2000SL33 T. Tanaka, T. Azuma, X. Fang, S. Uchida, C. Iwata, T. Ishida, Y. In, N. Maezaki, Synlett 2000,
33–36.2001JFC(109)123 V. A. Petrov, J. Fluorine Chem. 2001, 109, 123–128.2001JNP111 M. Musman, J. Tanaka, T. Higa, J. Nat. Prod. 2001, 64, 111–113.2001JNP939 S. Kehraus, G. M. Konig, A. D. Wright, J. Nat. Prod. 2001, 64, 939–941.2001JOC2854 A. R. Katritzky, B. Rogovoy, C. Klein, H. Insuasty, V. Vvedensky, B. Insuasty, J. Org. Chem. 2001,
66, 2854–2857.2002S195 M. Koketsu, F. Nada, H. Ishihara, Synthesis 2002, 195–198.
NR3
LiSe
NR3
R1R2NR1R2N
BuSe
NR3 BuISe + R1R2NLi +
27 28
Scheme 10
Functions Containing an Iminocarbonyl Group and at Least One Halogen 603
Biographical sketch
Tom Gilchrist was born in York, England and studied chemistry atKing’s College London, where he obtained his Ph.D. under the super-vision of Charles Rees. He taught for many years at Liverpool Univer-sity and retired from his post as Reader in 2002. He has publishedextensively on heterocyclic chemistry, with special interests in smallring compounds and cycloaddition reactions. He was a volume editorfor COFGT (1995), and has also edited several volumes of Progress inHeterocyclic Chemistry with Gordon Gribble. He is joint editor, withDick Storr, of Volume 13 of Science of Synthesis. Among his otherpublications is a textbook, Heterocyclic Chemistry.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 595–604
604 Functions Containing an Iminocarbonyl Group and at Least One Halogen
6.21
Functions Containing an
Iminocarbonyl Group and Any
Elements Other Than a Halogen
or Chalcogen
F. S´CZEWSKI
Medical University of Gdansk, Gdansk, Poland
6.21.1 IMINOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE NITROGENFUNCTION (AND NO HALOGEN OR CHALCOGEN FUNCTIONS) 606
6.21.1.1 Iminocarbonyl Derivatives with Two Nitrogen Functions 6066.21.1.1.1 N-Unsubstituted iminocarbonyl derivatives 6076.21.1.1.2 N-Alkyl iminocarbonyl derivatives 6176.21.1.1.3 N-Alkenyliminocarbonyl derivatives 6206.21.1.1.4 N-Aryliminocarbonyl derivatives 6206.21.1.1.5 N-Alkynyliminocarbonyl derivatives 6226.21.1.1.6 N-Acyliminocarbonyl derivatives 6236.21.1.1.7 N-Cyanoiminocarbonyl derivatives 6256.21.1.1.8 N-Haloiminocarbonyl derivatives 6266.21.1.1.9 N-Chalcogenoiminocarbonyl derivatives 6276.21.1.1.10 N-Aminoiminocarbonyl derivatives 6306.21.1.1.11 N�P, N�As, N�Sb, and N�Bi iminocarbonyl derivatives 6326.21.1.1.12 N�Si, N�Ge, and N�B iminocarbonyl derivatives 638
6.21.1.2 Iminocarbonyl Derivatives with One Nitrogen and One P, As, Sb, or Bi Function 6396.21.1.2.1 N-Alkylimino derivatives with one P or As function 6396.21.1.2.2 N-Arylimino derivatives with one P function 6406.21.1.2.3 N-Acylimino derivatives with one P function 6406.21.1.2.4 N-Haloiminocarbonyl derivatives with one P function 6416.21.1.2.5 Hydrazono derivatives with one P function 6416.21.1.2.6 Diazonium derivatives with one P function 6416.21.1.2.7 N,N-Dialkyliminium derivatives with one P function 642
6.21.1.3 Iminocarbonyl Derivatives with One Nitrogen and One Metalloid Function 6446.21.1.3.1 Silicon derivatives 6446.21.1.3.2 Boron derivatives 645
6.21.1.4 Iminocarbonyl Derivatives with One Nitrogen and One Metal Function 6456.21.1.4.1 Main metal derivatives 6456.21.1.4.2 Transition metal derivatives 645
6.21.2 IMINOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE P, As,Sb, OR Bi FUNCTION (AND NO HALOGEN, CHALCOGEN, OR NITROGENFUNCTIONS) 647
6.21.2.1 Iminocarbonyl Derivatives with One P, As, Sb, or Bi Function andOne P, As, Sb, or Bi Function 647
6.21.2.1.1 Bis(phosphino)iminocarbonyl derivatives 6476.21.2.1.2 Bis(phosphinyl)iminocarbonyl derivatives 6496.21.2.1.3 Iminocarbonyl derivatives with P function and one P, As, Sb, or Bi function 650
605
6.21.2.1.4 Iminocarbonyl derivatives with one As, Sb, or Bi functionand another As, Sb, or Bi function 650
6.21.2.2 Iminocarbonyl Derivatives with One P, As, Sb, or Bi Functionand One Si, Ge, or B Function 650
6.21.2.2.1 Iminocarbonyl derivatives with one P function and one Si, Ge, or B function 6506.21.2.2.2 Iminocarbonyl derivatives with one As, Sb, or Bi function and one Si, Ge, or B function 651
6.21.2.3 Iminocarbonyl Derivatives with One P, As, Sb, and Bi Function and One Metal Function 6526.21.2.3.1 Iminocarbonyl derivatives with one P function and one metal function 6526.21.2.3.2 Iminocarbonyl derivatives with one As, Sb, and Bi function and one metal function 6536.21.2.3.3 N-Unsubstituted iminocarbonyl derivatives 6536.21.2.3.4 N-Alkyl- and N-aryliminocarbonyl derivatives 6536.21.2.3.5 N-Haloiminocarbonyl derivatives 6546.21.2.3.6 N-Aminoiminocarbonyl (diazomethane) derivatives 6546.21.2.3.7 N-Silyliminocarbonyl derivatives 654
6.21.2.4 Iminocarbonyl Derivatives with One Metalloid Function and One Metal Function 6556.21.2.4.1 N-Alkyl- and N-aryliminocarbonyl derivatives 6556.21.2.4.2 N-Aminoiminocarbonyl (diazomethane) derivatives 655
6.21.3 IMINOCARBONYL DERIVATIVES CONTAINING TWO METAL FUNCTIONS 655
6.21.1 IMINOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE NITROGENFUNCTION (AND NO HALOGEN OR CHALCOGEN FUNCTIONS)
6.21.1.1 Iminocarbonyl Derivatives with Two Nitrogen Functions
Iminocarbonyl derivatives (guanidines) can be obtained according to the routes depicted inScheme 1. The following sections are ordered by type of substituents on the imino N2-atom.
SNR4R5
NR2R3
XNR4R5
NR2R3
ONR4R5
NR2R3
NNR4R5
NHR3
NNR4R5
NR2R3R1 R1R1
NCl
Cl
C NR3
R2
N NR1
NR3
C
1
MeI (or Me2SO4)
X = SMe, Cl, SO3H
MeI or COCl2 or POCl3
X = OMe, Cl, Cl2PO2
2
R1NH2
R2Hal
4
i. R2R3NH
6
ii. R4R5NH
R4R5NHR4R5NH
7
or COCl2 or peracid
NH3, Alk-NH2
+
3
5
8
Scheme 1
606 Functions Containing an Iminocarbonyl Group
6.21.1.1.1 N-Unsubstituted iminocarbonyl derivatives
Most methods for the preparation of N-unsubstituted iminocarbonyl derivatives are based on thereaction of primary or secondary amines with electrophilic precursors of the guanidine moiety.The guanylating precursor can be generated from various functions. Thiouronium salts of type 2are generated by reacting thioureas 1 with trialkyl oxonium salts, alkyl halides, chlorinatingagents, or peracids. Similarly, strong alkylating or chlorinating agents are also used for generationof electrophilic imino N2 centers from ureas 3. Compounds of type 2 react with amines in theclassic reaction known as the Rathke guanidine synthesis.
The direct reaction of 1-alkyl thiourea derivatives 1 with ammonia in the presence of zinc(II) orlead(II) salts gives rise to the formation of N-unsubstituted iminocarbonyl derivatives. Alterna-tively, 1,3-dialkyl guanidines can be prepared from activated carbamate-protected 1-alkyl ureaand alkylamines in the presence of water-soluble carbodiimide followed by deprotection. Analo-gously, 1,3-di-t-butoxycarbonyl-thiourea is converted to 1-alkyl guanidines.
Carboxamidines of type 2 bearing heteroaromatic leaving group (X=pyrazol-1-yl) and espe-cially those N,N1-bisurethane protected (R1= t-BOC or PhCH2OCO) are able to react with weaknucleophiles such as aromatic amines <1995COFGT(6)639>.
(i) N-Unsubstituted iminocarbonyl derivatives from thioureas
Usually, the formation of guanidines from thioureas is achieved by application of couplingreagents such as mercury(II) salts, diisopropyl carbodiimide (DIC), 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide (EDCI) or Mukaiyama’s reagent leading to the intermediate formation ofactivated thiourea or carbodiimides. The following sections are ordered by type of the couplingreagent. Moreover, due to recent developments in the solid-phase synthesis, the solution-phaseand solid-phase protocols will be discussed separately.
(a) N-Unsubstituted iminocarbonyl derivatives from thioureas using mercury(II) salt as couplingreagent. Solution-phase methods. In 1993 Kim and co-workers reported a facile synthesisof bis(t-BOC)-protected guanidines of type 10 from thiourea 9 R2,R4=H, R3,R5= t-BOC pro-moted by HgCl2 <1993TL7677>. This method followed by deprotection with TFA offers anefficient synthesis of terminal guanidines (Equation (1)).
BOCHN NHBOC
S HgCl2
R1R2N NHBOC
NBOC H+
R1R2N NH2
NH
BOCN=C=NBOCR1R2NH
10
9 ð1Þ
A synthetic method for internal guanidines has also been developed, employing as the key stepa nucleophilic substitution of bis(t-BOC)-protected terminal guanidines 10 <1995SL815>. Thesecond substituent, R2, was introduced as an electrophile (formation of 11), andt-BOC-deprotection completed the synthesis of internal guanidines 12 (Equation (2)). An analo-gous phase-transfer-catalyzed alkylation of 10 has also occurred regioselectively at one of thecarbamate nitrogens and the reaction proved to be tolerant to a wide range of functional groupson the guanidine including esters, amines, ketones, alcohols, and alkenes <2003JOC2300>.
R1R2N N-t-BOC
N-t-BOC N-t-BOC
N-t-BOC R1R2N NHR3
NH
R1R2NR3
10 1211
R1, R2 = H, alkyl; R3 = alkyl, Bn; 50–95%
i. NaH; ii. R3X, DMF, 0 °C to rt
ii. R3X, Bu4N+ I–, KOH, DCM/H2O, rt, 4 h
i or ii TFA
H
ð2Þ
Functions Containing an Iminocarbonyl Group 607
HgCl2-promoted guanylation was further studied with variously substituted thioureas 13 andthe scope and limitations were presented by Ko and co-workers <1997T5291>. The process wasfound to be effective with thioureas containing at least one activating group. Such N-conjugatedgroups include N-carbonyl (acyl, alkoxycarbonyl, carbamoyl), N-cyano, N-sulfonyl, and N-arylsubstituents (Equation (3)).
R1HN NHX
S
R1HN NR2R3
NX
13
i. R2R3NH, HgCl2, Et3N, DMF, rt
i
R1 = cyclohexyl, p-nitrophenyl; X = COR4 ; CN, SO2R4
R2R3NH = tetrahydroisoquinoline, aniline, p-methoxyaniline; 41–95%
ð3Þ
A nickel-boride-promoted guanylation of amines with N,N0-bis(t-BOC)thiourea 13 has alsobeen described <2000USP6100428>.
Solid-phase methods. A convenient solid-phase synthesis of ribonucleic guanidines 14 includingabstraction of the sulfur atom from fluorenylmethoxycarbonyl (Fmoc)-protected thiourea byHg2+ was described <2002T867> (Scheme 2).
Mercury(II) oxide proved to be a coupling reagent capable of activating the thiourea sulfurfragment for substitution without elimination leading to the intermediate carbidiimides<2000OL3563>. Resin-bound thiourea 15 bearing two substituents at one of the nitrogenatoms reacted with ammonia and primary or secondary amines in the presence of HgO. Thecleavage with 10% TFA in CH2Cl2 yielded guanidines of type 16 in the form of trifluoroacetatesalts (Scheme 3).
ON
H2N
O OTBs
NH
O
O
O
HN
LCAA-CPG
OU
NHMMTr
HNTBsO
NHFmoc
S
HgCl2, DMF, rt
ON
HN
O OTBs
NH
O
O
O
HN
LCAA-CPG
OU
NHMMTr
HNTBsO NFmoc
Hunig's base
LCAA-CPG = long chain alkylamine-controlled pore glass (solid support)
14
U = uracyl
+
Scheme 2
608 Functions Containing an Iminocarbonyl Group
(b) N-Unsubstituted iminocarbonyl derivatives from thioureas using carbodiimide as couplingreagent. Solution-phase methods. Following the procedure elaborated by Poss and co-workers<1992TL5933> the water-soluble carbodiimide EDCI hydrochloride) was used for the synth-esis of guanidinium derivatives 18 starting from carbamoyl isothiocyanates <2000JOC1566,2002TL565>. The carbamoyl thiourea 17 obtained from ethoxycarbonyl isothiocyanateand hindered amines was coupled to a second amine in the presence of EDCI, forming1,3-disubstituted and 1,1,3-trisubstituted guanidines through either stepwise or one-potsynthesis. The deprotection of the products was carried out using Me3SiBr under reflux inDMF followed by protonation with methanol, without cleaving of the functional groups(Scheme 4).
Solid-phase methods. A practical solid-phase synthesis that uses Rink amide resin as anamine component in reacting with aromatic isothiocyanates and aliphatic amines to give1,3-disubstituted guanidine of type 22 was described <2001TL2273>. The commercial Rinkamide resin 19 was deprotected with 25% piperidine/DMF, and then treated with an isothio-cyanate to give the resin-bound thiourea 20, which, in turn, was subjected to guanylation with anamine in the presence of DIC and Hunig base (DIPEA) to give the resin-bound guanidine 21.The disubstituted guanidine 22 was cleaved off under mild Rink resin cleavage conditions(Scheme 5).
A series of diverse guanidine compounds 25 (Scheme 6) were obtained based on a tracelesslinker approach to the solid-phase synthesis, utilizing resin-bound acyl isothiocyanate 23<1999TL3999>. This precursor undergoes addition reactions with a variety of amines to form
O
Cl
NN
NHR1
O
Cl
NN
NR1
S NHR2
O
Cl
NN
NR1
R3N NHR2
R1HN NHR2
NR3
i. NaH, DMF
ii. R2NCS, 2 h, rt
15
R3NH2, MeCN
HgO, 12 h, 45 °C
TFA, DCM
5 min, rt
R1 = alkyl, alkenyl, benzyl; R2
= alkyl, aryl; R3 = H, alkyl
16
Scheme 3
EtO N
CO
SEt
O NR1R2
S
EtO N
O
NR3R4
NR1R2
H2N NR3R4
NR1R2
X
R1R2NH
DCM, THF
R3R4NH
EDCl, Et3N, DCM
17
i, ii
i. Me3SiBr, DMF, reflux; ii. Methanol
18
+ –
72–79%
Scheme 4
Functions Containing an Iminocarbonyl Group 609
the corresponding acyl thioureas 24. In the second step, a resin-bound guanidine formation ispromoted through desulfurization with DIC. Cleavage of acyl guanidine is affected by treatmentwith TFA.
A polymer-assisted synthesis (PAS) methodology to obtain guanidines 28, which combinesadvantages of traditional solution-phase chemistry with the application of polymeric reagentswas developed as shown in Scheme 7 <2002TL7105>. Thus, N,N0-bis(t-BOC)thiourea 9 iscoupled with an amine with the use of polymer-supported carbodiimide 26. In order to removea by-product (bis-(t-BOC)carbodiimide), PS-trisamine 27 was added as a scavenger. Furtherdeprotection with TFA afforded terminal guanidines in very good yield.
(c) N-Unsubstituted iminocarbonyl derivatives from thioureas using Mukaiyama’s reagent.Solution-phase methods. Mukaiyama’s reagent was examined as a replacement for toxic heavy metalsalts to promote formation of carbodiimides from thioureas <1997JOC1540>. Primary and second-ary aliphatic and aromatic amines subjected to the reaction with N,N0-bis-(t-BOC)thiourea 9 andMukaiyama’s reagent resulted in the formation of the corresponding N,N0-bis-(t-BOC)guanidines oftype 10 in 21–91% yields (Equation (4)).
H2N NR1
NR2R3
NHFmoc NH
NHR1
S
NH
NR1
NR2R3
22
i, ii
2019
iii
iv
21
i. 25% Piperidine, DMF; ii. R1NCS, DCM, rt, 8 h;
iii. R2R3NH, DIC, DIPEA, CHCl3, 50 °C, 2 days; iv. 25% TFA, DCM, rt, 1 h
Scheme 5
HN NHR1
NR2R3
COOHO
NCS
O
HN CNHR1
S
O
HN CNHR1
NR2R3
25
i. (COCl)2, DMF
ii. But4N
+ NCS–
iii
iv
iii. R2R3NH, EDC, DIPEA, CHCl3 or DMF; iv. TFA, CHCl3, MeOH, 45–60 °C, 24–72 h
23
24
DMF
R1NH2
Scheme 6
610 Functions Containing an Iminocarbonyl Group
t-BOCHN NH-t-BOC
S
t-BOCHN N-t-BOC
NR1R2NMe
Cl
I–
R1R2NH, DMF9
R1 = H, alkyl, R2 = alkyl, aryl
10
+
ð4Þ
Solid-phase methods. An interesting strategy for generating a wide variety of guanidines 32 bysolid-phase synthesis was developed by Josey and co-workers <1998TL5899>. In one-pot,thiourea was deprotonated with 2 equiv. of sodium hydride, treated with the carbonylimidazoleresin 29, and then capped with t-butyl dicarbonate to afford 30. Coupling of the thiourea 30 withprimary and secondary amines in the presence of Mukaiyama’s reagent afforded the desiredproducts 31 in good yields (Scheme 8).
(ii) N-Unsubstituted iminocarbonyl derivatives from isothioureas
Solution-phase methods. Bis-(t-BOC)-protected guanidines 34 were obtained in 77–89% yieldsby treatment of the commercially available N,N0-bis-BOC-S-methyl thiourea 33 with hinderedaliphatic and aromatic amines in the presence of HgCl2 <2000SC2933>. This protocol can be usedfor the preparation of monoaryl internal guanidines (Equation (5)).
H2N NH
NArR1
O N
O
N O NH
O
NH
SBOC
O NH
O
NBOC
NArR1 Pr3SiHi
32
i, ii ArR1NH
Mukaiyama’s reagent
TFA, DCM
i. NaH, thiourea, THF; ii. (BOC)2O, THF
29 30
31
Scheme 8
H2N NH
NR1R2
BOCHN NHBOC
S NC
N
NH
N
NH2
NH2
BOCHN NBOC
NR1R2
28
R1R2NH
26
27
i.
ii.
iii
iii. 25% TFA in DCM
9+87–95%
Scheme 7
Functions Containing an Iminocarbonyl Group 611
t-BOCHN N-t-BOC
SMe
33
CH2Brt-BOCN N-t-BOC
SMeNH2
t-BOCN N-t-BOC
HN
i. KOH, TBA, toluene, 60 °C, 4 h; ii. HgCl2, Et3N, DMF, rt to 60 °C
i i ii34
ð5Þ
Solid-phase methods. 1,3-Disubstituted guanidines 37 can also be prepared from isothioureas onthe solid phase <1998TL5701>. The reaction of Merrifield resin-bound bis-(t-BOC)thiopseu-dourea 35 with alcohols in the presence of Ph3P and diisopropyl azodicarboxylate (DIAD) gaveN-alkylated resin-bound intermediate 36. The Mitsunobu reaction is relevant for most primaryand secondary alcohols, including benzylic and allylic alcohols. The N-alkylated products wereliberated from the resin as the bis-(t-BOC)-protected guanidines by exposure of 36 to excessmethanolic NH3 in DMF. Deprotection with TFA gave the corresponding N,N0-disubstitutedguanidines of type 37 (Scheme 9).
A similar approach has been utilized for a library synthesis of the analogs of the naturaldipeptide antibiotic TAN 1057A,B <2002MI469>.
1,3-Disubstituted guanidines were synthesized using the Rink amide MBHA resin-boundmethyl isothiourea 38 <1998TL2663>. Treatment with amines in DMSO afforded the corre-sponding guanidine derivative 39, which was cleaved from the resin with aqueous TFA to producecompounds 40 (Scheme 10).
S NH-t-BOC
N-t-BOC
S N-t-BOC
N-t-BOC
R1R2HN NHR1
NHi
35 36
ii, iii
37
i. R1OH, PPh3, DIAD, THF, 20 h; ii. NH3, MeOH, DMF or R2NH2, DMF; iii. TFA, DCM
R1 = alkyl, bn, allyl; R2 = H, alkyl, bn; 86–100%
Scheme 9
NH
O
HN NH
SCH3 N
H
O
HN NH
NR1R2
H2O H2N
O
HN NH
NR1R2
R1R2NH
DMSO, 70 °C
95% TFA
38 39
40
R1 = H, alkyl; R2 = alkyl; 64–89%
Scheme 10
612 Functions Containing an Iminocarbonyl Group
(iii) N-Unsubstituted iminocarbonyl derivatives from 1-H-pyrazole-1-carboxamidineand related precursors
Solid-phase methods. Inspired by the previously described guanylating agent 1-H-pyrazole-1-[N,N0-bis-(t-BOC)]carboxamidine 41 <1993TL3389>, Patek and co-workers developed anacid labile linker for solid-phase synthesis of substituted guanidines <2000JCO370>. Attach-ment of the linker to the TentaGel–NH2 resin was accomplished using ‘‘acidic’’ couplingconditions to prevent direct displacement of pyrazole with TentaGel–NH2. Most primaryand secondary aliphatic amines as well as arylamines reacted efficiently with 42, affordingnearly quantitative conversion to 1,1-disubstituted guanidines of type 43 (Equation (6)).
HN
OO
OHN
O
N
N-t-BOC
NR1R2N NH2
NH
42
i. R1R2NH, DMF, rt, 2 h
ii. TFA, DCM, H2O
43
ð6Þ
4-Nitro-1-H-pyrazole-1-[N,N0-bis-(t-BOC)]carboxamidine 44 (Figure 1) was also successfullyused for guanylation of resin-bound dipeptides <1999TL53>.
A comparison of guanylating agents N,N0-bis-BOC-thiourea 9 and agent1-H-pyrazole-1-[N,N0-bis(t-BOC)]carboxamidine 41 was performed on a series of primary andsecondary aliphatic and aromatic amines in both solution- and solid-phase resins <1997T6697>.Thiourea 9 performed well in solution and on solid-supported primary and secondary amines.Pyrazole 41 performed well in each case, except one aniline that failed to react.
The relative reactivity of guanylating agents 9, 33, and 41 (Figure 1) was also investigated inthe liquid-phase polymer-supported combinatorial synthesis of guanidines with piperazine andpiperidine scaffolds <1998SL1423>.
Benzotriazole methodology was further applied for the mild and efficient conversion of aminesto guanidines <1995SC1173>. Benzotriazole-1-carboxamidinium tosylate 45 (Figure 1) wasconveniently prepared by refluxing benzotriazole, cyanamide, and p-TsOH in 1,4-dioxane. Thereaction with primary and secondary amines including aromatic amines in the presence of DIEAat room temperature afforded the corresponding guanidines in good yields.
(iv) N-Unsubstituted iminocarbonyl derivatives from urethane-protected guanidinesand triflyl-diurethane-protected guanidines
The new classes of urethane-protected guanylation reagents 46 <1997JOC4867>, 47, and 48<1998JOC8432> as well as triflyl-protected 49 and 50 <1998JOC3804> (Figure 2) havebeen developed and utilized for the preparation of guanidines, guanidine-containing aminoacids, and peptides in both solution and solid-phase. These compounds are stable, crystallinesubstances that can remain stable indefinitely if refrigerated.
t-BOCHN NH-t-BOC
S
t-BOCHN N-t-BOC
SMe
t-BOCHN NBOC
NN
NN
N
H2NNH2
TsO–
9 33
t-BOCHN N-t-BOC
NN
O2N
44 4541
+
Figure 1
Functions Containing an Iminocarbonyl Group 613
Solution-phase methods. A series of arginine analogs 51 was synthesized via condensation of aprimary or secondary alcohol with guanylating reagents 47 and 48, under Mitsunobu conditionsto produce protected alkylated guanidines <1998JOC8432> (Equation (7)). A similar method-ology was applied for guanylating agents 33 and 41 <1999SL193>.
(CH2)n
CbzHN COOBn
CH2OH
(CH2)n
CbzHN COOBn
Nt-BOC
t-BOCN NH-t-BOC
47 , PPh3, DEAD
THF, reflux
51
––
–
ð7Þ
Guanylation of aliphatic and aromatic amines with bis-(BOC)- and bis-(Cbz)-protected triflyl-guanidines 49 and 50 gave the condensation products in 75–100% yields <1998JOC3804>.
Combinatorial synthesis of N,N0-bis-(t-BOC)-protected guanidines 52 based on the reaction ofguanylating reagents 49 and 50 with soluble polymer-bound diamines has also been developed<1999BMCL1517>. This combinatorial liquid-phase methodology has proved to be a useful toolfor constructing libraries containing diamine scaffolds (Equation (8)).
O
O
N(CH2)n
NO2
NH249
MeO
O
N(CH2)n
NO2
NH
N-t-BOC
NH-t-BOC
n = 1–3 52
ð8Þ
Using the triflyl-diurethane-protected guanidines 49, and 50, guanidine-containing, biologicallyimportant molecules, e.g., guanadrel, guanoxan, guanethidine, and smirnovine, were synthesized<1999S1423>. Moreover, guanidinoglycosides <2000JOC9054> and a novel library of guanidine-incorporated aminoglycoside antibiotics, guanidinopyranmycins was also synthesized using thereagent 49 <2002TL9255>.
With regard to the discussion about syntheses of bis-urethane-protected guanidines, it is worthnoting that a method of total deprotection of N,N0-bis-(BOC)guanidines of type 10 has beendeveloped <1997TL7865>. It was demonstrated that deprotection using SnCl4 proceededsmoothly in ethyl acetate at room temperature and led to the easily isolable guanidinium chlorides53 (Equation (9)).
t-BOCHN NH-t-BOC
NH
t-BOCHN NH-t-BOC
N-t-BOC
CbzHN NHCbz
NCbz
t-BOCHN NH-t-BOC
NTf
CbzHN NHCbz
NTf
46
49
Triurethane-protected guanidines:
Triflyl-diurethane-protected guanidines:
47 48
50
Figure 2
614 Functions Containing an Iminocarbonyl Group
i. SnCl4 (4 equiv.), AcOEt, rt, 3 h; ii. MeOH
R1, R2 = alkyl, aryl; 81–100%
N-t-BOC
NH-t-BOCR1R2N
NH
NH2R1R2NHCli, ii .
10 53 ð9Þ
Solid-phase methods. The solid-support-linked guanylating reagent 55 consisting of a urethane-protected triflyl guanidine attached to the resin via a carbamate linker was applied tothe synthesis of guanidines from a variety of amines under mild conditions <2001OL1133>.t-BOC-guanidine was immobilized on p-nitrophenyl carbonate Wang resin to form the protectedguanidine 54. Triflation of 54 resulted in the formation of resin-bound guanylating reagent 55.This reagent was used for the conversion of primary and secondary amines into resin-boundguanidines which were cleaved with TFA (Scheme 11).
Synthetic applications of diurethane-triflyl guanidines 49 and 50 were subject of a recentcomprehensive review <2000PAC347>.
(v) N-Unsubstituted iminocarbonyl derivatives from di(azolyl)methanimines
A mixture of di(benzotriazolyl)methanimines 56 and 57, obtained from the reaction of benzo-triazole with cyanogen bromide, has been developed as a versatile guanylating reagent for thegeneral synthesis of guanidines <2000JOC8080>. The sequential condensation of two amineswith 56 and 57 proved to be insensitive to electronic and steric effects and allowed for the use of awide diversity of amines. By this method it is now possible to obtain nonprotected tri- andtetrasubstituted guanidines 58 in high yields under neutral and mild conditions using an easypurification protocol (Scheme 12).
A similar approach for synthesizing guanidine compounds was reported usingdi(imidazol-1-yl)methanimine <2002JOC7553>.
OO
O NO2
N-t-BOC
NH2H2NO
O
HNNH2
N-t-BOC
OO
HNNSO2CF3
NH-t-BOC
NH
1R2RN NH2
i. Tf2O, Et3N, DCM, –78 °C to 0 °C; ii. R1R2NH, DCM, rt; iii. TFA, DCM
i ii, iii
54
55
R1, R2 = alkyl; 33–100%
Scheme 11
Functions Containing an Iminocarbonyl Group 615
(vi) N-Unsubstituted iminocarbonyl derivatives by miscellaneous methods
1,3-Disubstituted guanidines of type 59 were obtained upon solvolysis of 4,5-dihydro-2-thiazolaminehydrobromide and 5,6-dihydro-4H-1,3-thiazin-2-amine under the influence of aliphatic amines(Equation (10)) <2001CHE360>.
N(CH2)n
SNH2
H2OR1HN N
H
(CH2)nSHNH
59
R1NH2
n = 0, 1 n = 1, 2 R1 = Me, Et, CH2CH2OH
ð10Þ
Amidinoureas of type 60 could be prepared by the reaction of an acyl-S-methyl thiourea with anamine followed by removal of the acyl groups (Scheme 13) <1996TL1945>. Alternatively, amidi-nothiourea 61 was produced by reacting dicyandiamide and sodium thiosulfate in acidic mediumfollowed by neutralization with a base <1995OPP697>. This reaction involves three steps: (i) additionof two moles hydrogen chloride to dicyandiamide, (ii) addition of thiosulfuric acid and acidic hydro-lysis, and (iii) release of the free amidinothiourea (61, gutimine) by treatment with a base (Scheme 14).
The synthesis of 11C-labeled guanidines 62 was described by Langstrom and co-workers<1996JA6868>. The conversion of the 11C-labeled cyanamide to 11C-labeled guanidines was achievedin both supercritical ammonia and aqueous ammonia solutions. The latter method gave low and
NH
Bt1Bt1
NH
Bt2Bt1
NH
NR1R2Bt1
NH
NR1R2R1R2NBtH
NN
N
NN
N
57
R1R2NH
THF, rt, –BtH
R3R4NH
THF, ∆
Bt1 = Bt2 =
R1, R2 = H, alkyl, aryl; R3, R4 = H, Me, aryl
56
58
+
+
Scheme 12
SMe
NCbzH2N THF
SMe
NCbzNH
CbzHN
OCbzNCO
NR1R2
NCbzNH
CbzHN
O NR1R2
NHNH
CbzHN
O
R1R2NH
Et3N, DMF
i. H2 (60 psi), 20% Pd(OH)2/C, 96–99%
i
60 R1 = H, alkyl; R2 = alkyl
Scheme 13
616 Functions Containing an Iminocarbonyl Group
irreproducible yield as compared to performing the reactions in automated fluid synthesis (SFA)system. Using the SFA system designed for the use with supercritical ammonia, total radiochemicalyields of 11C-labeled guanidines of 30–85%were obtained for the aromatic amines and 2–36% for thealiphatic amines (Equation (11)).
RNH2
11CNBrRNH11CN
NH3RNH11CNH2
NHR = alkyl, Ar 62
ð11Þ
6.21.1.1.2 N-Alkyl iminocarbonyl derivatives
As shown in Scheme 1 preparation of N-alkyl guanidines may be carried out either directly fromthe reaction of thioureas with alkylamines in the presence of lead oxide or via S-alkyl isothiour-onium salts (2, X=SMe, SEt) or isouronium salts (2, X=OMe, Cl, Cl2PO2). For the synthesisof sterically hindered pentaalkyl guanidines use of the reactive chlorformamidinium (Vilsmeier)salts is preferred.
The bis-electrophilic guanidine precursor carbonimidic dichloride 6 upon reaction with 2 equiv.of the same amine or one each of two different amines gives tri-, tetra-, and pentaalkyl guanidines.
Trisubstituted guanidines are also derived from the reaction of carbodiimides 8, obtained bydehydration or desulfurization of ureas or thioureas, with an amine.
Reactions of alkyl cyanamides 7 with amines or amine salts give rise to the formation ofN-alkylguanidines in high yields.
The less common procedures involve either the reaction of complexes of mercury(II) chlorideand t-butyl isocyanide with mono- and dialkylamines or lithium aluminum hydride reduction ofvarious alkyl-substituted acyl guanidines (5, R1=acyl) <1995COFGT(6)639>.
During the 1990s, the following methods have been developed.Trichloroacetamides obtained via Overman [3,3] sigmatropic rearrangement are converted into
N,N0-dibenzyl-N0-alkyl guanidines <1994CL2299>. The key step is the conversion of carbodi-imide intermediate 63 into guanidine by rare earth triflates such as scandium or ytterbiumtrifluoromethane sulfonates (Scheme 15).
An original sequence for solution and solid-phase synthesis ofN,N0,N0-trisubstituted guanidines oftype 66 has been developed by Mioskowski and co-workers <2000CEJ4016>. The sequence involvesas key intermediate a bis-electrophilic chlorothioformamidine 64 that undergoes smooth nucleophilicaddition of a primary amine to afford the corresponding isothiourea. The guanidine 66 is thenobtained by heating the isothiourea 65 in the presence of a primary amine in toluene (Scheme 16).
In the analogous solid-phase synthesis, chloromethylpolystyrene (Merrifield resin) was usedinstead of benzyl chloride in the first step to give resin-bound dithiocarbonate.
A library of di- and trisubstituted guanidines of type 70 was synthesized in the process termed‘‘combinatorial synthesis on multivalent oligomeric support’’ (COSMOS) <1999TL4477>. Thesynthetic route consists of attaching thiourea onto the soluble tetravalent support 67, andconversion to the guanidine 68 in the presence of HgCl2 or via methyl isothiourea 69. Cleavagefrom the support in 20% TFA/DCM affords the guanidine 70 as the TFA salt (Scheme 17).
R1HN NHCN
NH 2HCl
R1HN NH
NH2 NH
ClCl–
Na2S2O3
R1HN NH
NH NH
SSO3H
H2O
R1HN NH
NH2 S
NH2
HSO4–
NH4OHR1HN N
H
NH S
NH2
R1 = H, alkyl; 71–95%
61
+
+
Scheme 14
Functions Containing an Iminocarbonyl Group 617
R1HN S
SBn
COCl2
R1N Cl
SBn
R2NH2
R1HN NR2
SBn R3NH2
R1HN NHR2
NR3
R1NH2
BnCl, CS2
THF, rt Toluene, 60 °C
Toluene, 60 °C Toluene, 100 °C
64
65 66
Scheme 16
HN (CH2)n
O
HNCR1
SHN (CH2)n
O
HNCNR1R2
NR1
HN (CH2)n
O
HNCNR1
SCH3
H2N (CH2)n
O
HNCNR1R2
NR1
R1R2NH
HgCl2, DMF
MeI, DMFDMSO, 100 °C
R2R3NH 20% TFA/DCM
67
69 70
68
Scheme 17
R OH
CCl3CN HN O
CCl3
R
HN CCl3
O
R
HN NHBn
O
REt3N
NC
R
NBn
BnNH2
HN NHBn
N
R
Bn
i. Overman [3,3] sigmatropic rearrangement
i
PPh3, CBr4
Sc(OTf)3 or Yb(OTf)3
63
BnNH2
Scheme 15
618 Functions Containing an Iminocarbonyl Group
Another facile solid-phase synthesis of N,N0,N0-substituted guanidines 75 from an immobilizedamine component is depicted in Scheme 18. The resin-bound amine 71 is reacted withdi-(2-pyridyl)thiocarbonate (DTP) to generate the isothiocyanate 72, which is then treated witharyl-/alkylamines to yield the corresponding resin-bound thiourea 73. Desulfurization of 73 isreadily achieved by treatment with triphenylphosphine dichloride. Further reaction with aryl-/alkylamines (formation of 74) followed by acidic cleavage with TFA yields N,N0,N0-substitutedguanidines 75 of excellent purity and in good yields <2002T1739>.
The solid-phase library synthesis of trisubstituted guanidines of type 78 was accomplished bydehydration of ureas 76 with p-TsCl in pyridine to give solid-supported carbodiimides 77 followedby nucleophilic addition of amines and cleavage of the solid support with TFA (Scheme 19)<2002JCO167>.
As shown in Scheme 20, trisubstituted guanidines of type 80 were synthesized on solidsupport via aza-Wittig coupling of alkyliminophosphorane with an aryl or alkyl isothiocyanateto generate the corresponding solid-supported carbodiimide 79, which was then reacted with aprimary or secondary amine <1997TL3377>.
Wang O (CH2)n
O (CH2)n
O (CH2)n
O (CH2)n
(CH2)n
O
NH2
DPTWang
O
NC
S
Wang
O
HN
NR1R2
SWang
O
N
NR1R2
NR3R4
HO
O
N
NR1R2
NR3R4
75
DCM, 20 °C
i. R1R2NH, N-methyl-2-pyrrolidine, 20 °C; ii. R3R4NH, Ph3P, C2Cl6, dry THF, 20 °C
ii
71 72
73 74
DCM, 20 °C
TFAi
Scheme 18
NR1
O
HN NR2
O
NR1
O
NC
NR2
HNR1
O
HN NR2
NR3R4
p-TsCl
Pyridine
i. R3R4NH, DMSO
ii. TFA, DCM
76 77
78
Scheme 19
Functions Containing an Iminocarbonyl Group 619
Preparation of differentially substituted guanidinium salts 81 from phosgenium salt by sequen-tially introducing secondary amines of markedly different reactivity was achieved as depicted inScheme 21 <1997JOC4200>.
6.21.1.1.3 N-Alkenyliminocarbonyl derivatives
Title compounds can be prepared by reacting Vilsmeier salts with ketone imines. Other methodsinvolve the reaction of 1,1,3,3-tetramethyl guanidine with either acetylenedicarboxylate or iso-butyraldehyde in the presence of catalytic amount of TsOH.
No further advances have occurred in this area since publication of chapter 6.21.1.1.3<1995COFGT(6)639>.
6.21.1.1.4 N-Aryliminocarbonyl derivatives
In general, the methods developed for syntheses of N-alkyl guanidines are also applicable to thepreparation of N-aryliminocarbonyl derivatives. Thus, they can be obtained from amidinium salts2 and urea derivatives 3, carbonimidic dichlorides 6, carbodiimides 8, and cyanamides 7 (Scheme1) <1995COFGT(6)639>. Since then, however, several new methods for the preparation of thisclass of compounds have been developed.
(i) N-Aryliminocarbonyl derivatives from guanidines
A straightforward synthetic approach to 6-guanidinopurines consists in the reaction of the6-chloropurine derivatives with guanidine in DMF solution in the presence of DABCO as catalyst<2002T2985>. Similarly, the 4-O-triisopropylphenylsulfonyl (OTPS) thymidine can be guany-lated directly in the presence of t-BuOK <1998TL547>.
NMe
Me Cl
ClN
Me
Me NR1R2
ClCl– N
Me
Me NR1R2
NR3R4
81
NH(Et)2
NH(Bn)2
NH(iPr)2
Cl–R1R2NH
Et3N, DCM
R3R4NH
Et3N, DCM
NHR1R2 NHR3R4 Yield (%)
Pyrrolidine 100
Pyrrolidine
Pyrrolidine 88
76
+ + +
Scheme 21
Rink NH
O
N3 Rink NH
O
N C N
H2N
O
HNN
NR1R2
i, ii
iii, iv
i. PhNCS, THF; ii. PPh3, THF, 25 °C; iii. R1R2NH, DMSO, 25 °C; iv. TFA, H2O, 25 °C
79
80
Scheme 20
620 Functions Containing an Iminocarbonyl Group
(ii) N-Aryliminocarbonyl derivatives from thioureas
Ramadas and co-workers have developed several methods for direct syntheses of N-aryl-substitutedguanidines 83 from N-arylthioureas 82. A rapid synthesis of N,N0-di- and N,N0,N0-trisubstitutedguanidines can be achieved using copper sulfate–silica gel in the presence of an amine (Scheme 22,Method A). This method, however, suffers from disadvantages involving the unstable carbodi-imide intermediate, use of costly copper salt, and the need for anhydrous conditions<1995TL2841>.
Desulfurization of monoaryl and N,N0-diarylthioureas with lac sulfur adsorbed on aluminafollowed by treatment with ammonia, diethylamine, or morpholine in the presence of trietha-nolamine provided the corresponding guanidines in 68–85% yields (Scheme 22, Method B).Hydrogen sulfide is effectively trapped by triethanolamine and, therefore, this process isbound to trigger commercial interest since pollution due to hydrogen sulfide is avoided<1996TL5161>.
Oxidation of N,N0-disubstituted thioureas using the previously unexploited reagents sodiummetaperiodate and sodium chlorite in aqueous medium provides another facile and high-yieldingroute to N-aryl guanidines (Scheme 22, Method C) <1997SL1053>.
R1HN NHR2
S
R1N NHR2
NR3R4
Ph
R1 R 2 R
3 R 4
Ph CH3 H
H
Ph Ph CH3 CH3
Ph Ph C6H11 H
Ph Ph C2H5 C2H5
Ph Ph Bn C2H5
o -Tolyl o -Tolyl C2H4OH H
H
Ph Ph H
Ph Ph H
Ph Ph Et Et
Ph Ph Morpholyl H
Ph C6H11 Morpholyl H
o -Tolyl H Morpholyl H
HPh Ph H
Ph Ph H C6H11
Ph Ph H Bn
Ph Ph Et Et
Ph Ph C6H11 C6H11
A
A
A
A
AAA
B
B
B
B
B
C
C
C
C
C
i, ii or iii, iv
Cond. Yield Method
i, ii 78
i, ii 75
i, ii 85
i, ii 90i, ii 80i, ii 75
i, ii 90
iii, iv 85
iii, iv 82
iii, iv 85
iii, iv 72
iii, iv 80
v, vi 76a, 80b
v, vi 84a, 81b
v, vi 68a, 65b
v, vi 76a, 80b
v, vi 60a, 53b
or v, vi
Method A: i. CuSO4, SiO2, TEA, THF; ii. R3R4NH, rt
Method B: iii. Lac sulfur on alumina, triethanolamine; iv. R3R4NH, reflux
Method C: v. NaIO4 or NaClO2; vi. R3R4NH, DMF–H2O, 80–85 °C
a NaIO4; b NaClO2.
82 83
(%)
Scheme 22
Functions Containing an Iminocarbonyl Group 621
(iii) N-Aryliminocarbonyl derivatives from isothioureas
The reaction of a variety of anilines with a new N-methylguanylating agent 85 was reported togive the corresponding N-aryl guanidines 86 (Scheme 23). Formation of 85 entailed reaction ofcommercially available N-methyl thiourea with (BOC)2O to provide 84. Treatment of 84 with2,4-dinitrofluorobenzene (Sanger’s reagent) furnished 85 in 86% yield <1996TL6815>.
Two solid-phase syntheses of libraries of N-aryl-substituted guanidinocarboxylic acids of type89 were described <2000JCO276>. The first method involving trapping of solution-phase carbo-diimides 87 by supported amines was used to produce N-aryl-N0,N0-dialkyl derivatives 88 (Scheme24). A limitation of this method was that the supported guanidines 88 tended to undergo anundesired intramolecular cyclization. The second solid-phase method (Scheme 25), featuringsupported carbodiimides 90 and solution-phase amines was devised to prepare N,N0-disubstitutedand N,N0,N0-trisubstituted guanidinocarboxylic acids 89.
(iv) N-Aryliminocarbonyl derivatives from carbodiimides
Alkylation of the highly electron-deficient amines with N-trityl-protected carbodiimides 91 asshown in Scheme 26 leads to the formation of N,N0-bis(aryl)guanidines 92 <1997TL6799>.The dehydration of N-trityl-N0-arylureas to the corresponding carbodiimides 91 is achievedusing the Burgess reagent.
6.21.1.1.5 N-Alkynyliminocarbonyl derivatives
The flash photolysis of phenylguanidinocyclopropenone leads to the formation of 2-(phenyl-ethynyl)-1,1,3,3-tetramethyl guanidine as a transient intermediate which, in aqueous solution, isconverted to an acyl guanidine <1995COFGT(6)639>.
t-BOCHN NMe-t-BOC
S
t-BOCN NMe-t-BOC
S
NO2O2N
H2N NHMe
NAr
85
Sanger’s reagent i. ArNH2, Et3N
ii. TFA
84 86
Scheme 23
R1HN NHR2
SC
R1N
NR2Wang O (CH2)n
O
NH2
Wang O (CH2)n
O
HN
NR1
NHR2HO (CH2)n
O
HN
NR1
NHR2
Mukaiyama’s reagent
84
DCM, Et3N, 25 °C
TFA, DCM
25 °C, 1 h
87
88 89
R1 = aryl, R2 = akyl; 53–96%
Scheme 24
622 Functions Containing an Iminocarbonyl Group
As shown in Scheme 27, the N-alkylideneynamines 94 can be prepared by the reaction ofperchlorobutyne with tetramethyl guanidine (TMG). The trichlorovinyl group of 93 is trans-formed by buthyllithium and chlorosilane into a silylethinyl moiety <1988TL5355>.
6.21.1.1.6 N-Acyliminocarbonyl derivatives
Title compounds (5, R5=acyl) are obtained by acylation of the free base of S-methyl isothio-uronium salts (2; X=SMe) followed by treatment with monoalkylamines (Scheme 1). Condensa-tion of unsubstituted or monosubstituted guanidines with acid esters gives monoacetylatedproducts. The preparation of di- and trisubstituted guanidines can be accomplished using acidchlorides or anhydrides. Reactions of guanidines with N,N-dimethylthiocarbamoyl chloride orisothiocyanates give rise to the formation of corresponding 2-(thiocarbamoyl)guanidines. Simi-larly, 2-amidinoureas (5; R1=ArNHCO) can be obtained by reacting guanidines with arylisocyanates (ArNCO) or carbamoyl chlorides (ArNRCOCl) <1995COFGT(6)639>.
The following methods have been developed since the publication of COFGT (1995).
ONH
NHO
SR1
ON
C
O
N
R1
ONHO
N
NR2R3
R1
HONHO
N
NR2R3
R1
i. Mukaiyama’s reagent, DCM, Et3N, 25 °C, 1 min
i
R1R2NH TFA, DCM
25 °C, 1 h 25 °C, 10 h
90
89
R2, R3 = alkyl; 56–94%
Scheme 25
R1HN NHR2
O DCM, 25 °C
R1NC
NR2
Et3N SO
ON
OMeO
N NH2 N NH2
NHR1
Burgess’ reagent 91
i. NaH, DMF; ii. 91; iii. 4N HCl, i -PrOH
i, ii, iii
R1 = aryl, R2 = Tr
92 R1 = aryl
–
++
N
Scheme 26
Functions Containing an Iminocarbonyl Group 623
(i) Solution-phase methods
As shown in Scheme 28 N-benzoyl thioureas can be easily converted to N-benzoyl guanidinesof type 95 by HgCl2 promoted reaction with alkyl and aryl amines <2001T1671>. N-benzoylthioureas are also converted to the corresponding acyl guanidines using an amine in the presenceof coupling reagents such as EDCI or 2-chloro-1-methylpyridinium iodide (Mukaiyama’s reagent)<2002TL57>. Bismuth nitrate pentahydrate was also found to serve as an effective reagent forguanylation of N-benzoyl thioureas (Scheme 28) <2002TL49>.
An improved procedure for the generation of 1-aroyl-S-methyl isothiourea derivatives 96 consistsin the reaction of acid chloride (1 equiv.) in ether with S-methyl isothiouronium sulfate (2 equiv.) insodium hydroxide under ice-cold conditions (Scheme 29). Subsequent condensation with aromaticand aliphatic amines gives the desired N-acyl guanidines 97 in 48–74% yields <2001SC2491>.
(ii) Solid-phase methods
N-acylation of the resin-bound S-methyl isothiourea 98 with carboxylic acid using7-azabenzotriazol-1-yloxytris(pyrrolidino)phosphonium hexafluorophosphate (PyAOP) as cou-pling reagent followed by displacement of the thiomethyl group with ammonia, a variety of
Ph NH
NHR1
O S
Ph N NHR1
O NHR2i or ii or iii or iv
i. R2NH2, HgCl2, Et3N, DMF, 60–81%
ii. EDCI, DAMP, Et3N, 30–74%
iii. Mukaiyama's reagent, 75%
iv. Bi(NO3)3.5H2O, DMF, 60–81%
R1, R2 = alkyl, aryl 95
Scheme 28
O
R1 Cl SMe
NHH2N
NaOH
O
R1 HN SMe
NH O
R1N NHR2
NH20–5 °C
R2NH2, Et3N
Xylene, reflux
96
R1 = aryl, thienyl; R2 = alkyl, aryl
97
+
Scheme 29
C CC
Cl
ClCl
C Cl CCC
Cl
ClCl
C N CN(Me)2
N(Me)2
C C C N CN(Me)2
N(Me)2CMePh2Si
2TMG i. 2BuLi
ii. ClSiMePh2
93
94
Scheme 27
624 Functions Containing an Iminocarbonyl Group
primary or secondary amines or aniline resulted N-acyl-N0-alkyl(aryl)guanidines 99 which areliberated from the resin upon exposure to TFA (Equation (12)) <2001TL1259>.
OHN SMe
O NH R1 N NR2R3
O NH2i, ii, iii
i. R1PyAOP, DIPEA, NMP; ii. R2R3NH, NMP; iii. TFA, DCM
98 99ð12Þ
In a similar manner, starting from amino acid immobilized on polystyrene Wang or Rinkamide resin, the synthesis of N-acyl-N0-carbamoyl guanidines can be achieved <1998TL9789>.
The resin-bound pyrazole carboxamidine 100 upon deprotonation with lithium hexamethyl-disilazide (LiHMDS) followed by treatment with an acyl chloride affords the resin-bound guanylat-ing agent 101. The latter compound reacts with an amine to provide resin-bound disubstitutedguanidine which is cleaved with TFA at room temperature (Scheme 30) <2001JOC2161>.
6.21.1.1.7 N-Cyanoiminocarbonyl derivatives
Title compounds are most often prepared from thioureas and their derivatives. These methodsinclude (i) the reaction of an N,N0-disubstituted thiourea with lead cyanamide, (ii) reaction ofan amine with N-cyano-N0,S-dimethyl isothiourea, and (iii) the reaction of an amine withdimethylcyanodithioimidocarbonate followed by treatment with alkylamine.
2-Cyanoguanidines are also obtained in high yields by reacting cyanamide (H2NCN) withcarbodiimides (8; R1=aryl, R2=alkyl) in the presence of catalytic DIPEA (Hunig base).Condensation of sodium (or lithium) dicyanamide with monoalkylammonium salts yields thecorresponding monosubstituted 2-cyanoguanidines (5; R1=CN, R2,R3=H, R4=alkyl) (Scheme1) <1995COFGT(6)639>.
Recently, three novel methods for preparation of 1,3-substituted cyanoguanidines 104 havebeen developed. One involves the reaction of commercially available diphenylcyanocarbonimidate102 with anilines and subsequent treatment of the obtained cyano-O-phenylisourea 103 withalkylamines (Scheme 31) <1997CPB2005, 2001BMCL1749>. Dimethyl cyanodithioiminocarbo-nate 105 reacts similarly <1994TL8085>.
WangO
HN NH
O NN
WangO N
HN
O NN
R1
OR2R3N N
HR1
NH Oi, ii iii, iv
i. LiHMDS, THF, 0–5 °C; ii. R1COCl; iii. R2R3NH, THF; iv. TFA, DCM, 2 h
R1 = aryl, alkyl, bn; R2, R3 = alkyl, aryl; 61–88%
100 101
Scheme 30
PhO O
PhN
CN
Ar
HN O
PhN
CN
Ar
HN NHR1
NCN
ArNH2, rt, 14 h
73%
R1NH2, base
23–73%
R1 = alkyl, aryl; base = Et3N, Py
102 103 104
Scheme 31
Functions Containing an Iminocarbonyl Group 625
As shown in Scheme 32, dimethyl cyanodithioiminocarbonate 105 was converted into2-methylthio-N,N0-dicyano-1,3-diaza-2-propenide 106 by reaction with cyanamide in the presenceof K2CO3. Alternatively, the reaction of 105 with disodium cyanamide in N,N0-dimethylacetamidegave disodium N,N0,N0-tricyanoguanidine 107 <1995CM2213>.
N,N0-diarylcyanoguanidines 109 were synthesized from N-cyano-O-phenylureas 108 and aryl-amines. In analogy with the reaction in which the Weinreb amide is formed, trimethylaluminumwas employed to promote this displacement (Equation (13)) <1994TL8085>.
NCN
ONH
R1
NH2
NCN
NH
NH
R1
i ii
i. Diphenylcyanocarbonimidate, AcCN, reflux, 2 h
ii. Aniline, trimethylaluminum, DCM, 65 °C, 2 h
108 109ð13Þ
The highly reactive di(imidazol-1-yl)cyanomethanimide 110 readily reacts at room temperaturewith both alkyl- and arylamines to yield the corresponding cyanocarboximidazoles 111. In turn,111 is converted to cyanoguanidines of type 112 in refluxing THF (Scheme 33) <2002JOC7553>.
6.21.1.1.8 N-Haloiminocarbonyl derivatives
Many of the N-haloguanidines are unstable and/or explosive; therefore, most halogenations ofguanidines are carried out on laboratory scale. These compounds are usually prepared by directelemental halogenation of appropriately substituted guanidines. For example, perfluoroguanidinecan be obtained by reaction of guanidine with elemental fluorine. 2-Chloro-1,1-dialkyl guanidinesare prepared by oxidation with sodium hypochlorite.
NCN
SMeMeS
NCN
MeS
NCN
Na+N
CN
N
NCN
CN
2Na+
105
106
107
i ii
i. H2NCN, THF, K2CO3, ∆, 12 h,
ii. 2Na2NCN, DMAC, 120–140 °C, 2 h,
83%
67%
––
–
Scheme 32
NCN
NNN N
NCN
NR1R2N N
NCN
NR3R4R1R2N
R1R2NH
THF, rt
R3R4NH
THF, reflux
110 111 112
Scheme 33
626 Functions Containing an Iminocarbonyl Group
An interesting example, where 2-haloguanidine was prepared by a method other than the directnitrogen–halogen formation is the reaction of pentafluoroguanidine with alkyl- or arylamines atlow temperatures. The initially formed adduct upon warming loses difluoroamine to give atrifluoroguanidine.
No further advances have occurred in this area since the publication of chapter 6.21.1.1.8 in<1995COFGT(6)639>.
6.21.1.1.9 N-Chalcogenoiminocarbonyl derivatives
(i) Oxygen derivatives
The reaction of hydroxylamines with S-alkyl isothioureas and chlorformamidines 2, cyanamides7, and carbodiimides 8 all give rise to the formation of the hydroxyguanidines (Scheme 1).
N-Alkoxyguanidines are prepared analogously starting from O-alkylhydroxylamines in place ofhydroxylamines. They are also synthesized by alkylation of hydroxyguanidines with alkyl halides.However, acylation of hydroxyguanidines gives the corresponding acetoxy- or benzoyl-oxyguanidines <1995COFGT(6)639>.
Recently, guanylations of thioureas with O-benzylhydroxylamine have been described. Con-struction of benzyloxyguanidine group 113 can be achieved either following the activation of thethiocarbonyl group by mercury(II) oxide and subsequent displacement with O-benzylhydroxyl-amine <1994JCS(P1)769> or using HgCl2 as coupling reagent <2000JOC2399>. Hydrogenationof the benzyl group using 20% Pd(OH)2 as the catalyst at 0 �C yields the hydroxyguanidinederivative 114 (Scheme 34).
A new convenient reagent for N-hydroxyguanylation has also been described. According toScheme 35, 1-benzyloxycarbonylthiourea 115 was synthesized from benzyl chloroformate intwo steps. Reactions of this protected urea with various amines using HgCl2 in the presence ofEt3N furnished hydroxyguanidines 116 in 37–67% yields <1997SC315>.
(ii) Sulfur derivatives
The most convenient route to sulfonyl guanidines consists in the condensation of an arylsulfonylchloride with guanidine or the reaction of arylsulfonamides with S-alkyl isothioureas. N-(alkylamino-sulfonyl)guanidines can be prepared by reacting N,N-dialkyl-N0-chlorosulfonylchloroformamidineswith primary or secondary amines. The reaction of S,S-dimethyl-N-arylsulfonyliminodithiocarbon-imidate orN-Ts-carbonimidic dichloride with amines leads to the formation of N-sulfonyl guanidines.
S
NHR2R1HN
N
NHR2R1HN
OBnN
NHR2R1HN
OHi, ii (or iii) iv
i. BnONH2 3.HCl; ii. HgO, Et N, Et2O, rt
iii. HgCl2, TEA, DMF, rt; iv. Pd(OH)2/C, H2, MeOH, 0 °C, 10 min
113 114R1, R2 = alkyl
Scheme 34
CbzClKSCN
CbzNCSH2NOBn
S
NHOBnCbzHN
NR1R2
NHOBnCbzHN
115
R1R2HN, HgCl2
Et3N, DMF
116
Scheme 35
Functions Containing an Iminocarbonyl Group 627
Another method for the synthesis of sulfonyl guanidines involves the reaction of N-sulfonyl-N0-alkyl carbodiimides with alkylamines. Cycloaddition reactions of sulfonyl isothiocyanates andguanidines, sulfonyl isothiocyanates and thiourea or N-sulfinyl-sulfonamides and thioureas giverise to the desired sulfonylguanidines <1995COFGT(6)639>.
In recent years, a new reagent (117; Equation (14)) capable of guanylating primary amineseffectively has been developed <2001OL2341>. The reaction of pyrazole 117 with aliphaticamines at room temperature affords N-Ts-protected guanidines 118 in quantitative yields, whileaniline and t-butylamine are less reactive. No reaction takes place with p-nitroaniline andpiperidine.
N
NH2t-BOCN
NN
NTst-BOCHN
NNHR1
NTst-BOCHN
117
TsCl, NaH, THF RNH2, THF, rt
118
ð14Þ
A series of N-aryl-N0,N0-dimethyl-N0-trifluoromethylsulfonyl guanidines 120 were prepared byreacting dimethyl cyanamide with triflic anhydride (Tf2O) followed by treatment of intermediaryformed 2,3-bis-(trifluoromethylsulfonyl)-1,1-dimethylisourea 119 with aromatic amines (Scheme 36)<1995SL161>.
HgCl2 or EDCI were applied as coupling reagents to the syntheses of sulfonyl- and sulfamoyl-guanidines of type 121 from thiourea precursors (Scheme 37, methods A and B, respectively)<2000TL8075>. Similar results were obtained using HgO <1996SC4299>.
Synthesis of N,N0-substituted guanidines 123 was also developed via an aromatic sulfonyl-activated thiourea intermediate 122 <2003JOC1611>. A primary amine was first turned into apentafluoromethyl thiocarbonate. This allowed for the synthesis of the arylsulfonyl-activatedthiourea 122 using PbfNHK as nucleophile (Scheme 38). Treatment of 122 with an amine inthe presence of Mukaiyama’s reagent produced subsequent guanidine 123 in very good yield. Thereaction works for either primary or secondary amine nucleophiles, including the stericallyhindered t-butylamine as well as diisopropylamine, both of which are known to cause problemsin other guanidine syntheses performed in solution. The above was also adopted to solid-phasesynthesis of functionalized amino acids. An amino acid attached to Rink amide MBHA resin wasturned into the desired guanidine derivative through direct guanylation with Pbf-activatedthiourea <2003JOC1611>.
N CMe
MeN
Me
Me OTf
NTfN
Me
Me NHR1
NTf
Tf2O ArNH2
DCM, 20 °C
119 120
30–58%
R1 = Ph, 2-pyrimidinyl
N
Scheme 36
S
NNa
R1HNSO2R1
NR2R3
NR1HNSO2R1NH2SO2R1
i. NaH
ii. R1NCS
iii (or iv)
70–90%
iii. HgCl2, Et3N; (method A) iv. 1-Ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride (EDCI); (method B)
121
R1 = Me, Ph, NH2; R2 = aryl, alkyl; R3 = alkyl; phenyl; R4 = H, Pri
Scheme 37
628 Functions Containing an Iminocarbonyl Group
N-Sulfonyl guanidines 124 were obtained from the reaction of alkyl isocyanides with aromaticamines in the presence of chloramine T (Equation (15)). The synthesis affords N-tosyl guanidinesby an experimentally simple one-pot procedure but, surprisingly, by employing alkylamines,instead of anilines, the reaction did not occur <1995TL2325>.
ArNH2 TsNNaClN
R1HN NHAr
Ts
124
TEBA, DCM
rt, 20 °C RNC: + + ð15Þ
N-Arylsulfonyl-N0-(pyrimidin-2-yl)-guanidines were prepared by reacting the correspondingN-acylsulfonyl guanidines with pyrimidin-2-yl-trimethylaminium chloride at room temperaturefor 48 h <2001KGS349>.
As depicted in Scheme 39, 2-mercaptobenzenosulfonylguanidines and corresponding ami-noguanidines of type 125 were obtained by selective aminolysis or hydrazinolysis of the3-alkylamino-1,4,2-benzodithiazine derivatives <2002EJM285, 1992MI93>.
Upon treatment of N-carbamoylmethyl-N0-tosylguanidines 126 with primary amines, an unpre-cedented intramolecular transamination reaction was observed <2003OL3851>. The reactionleading to N-tosylguanidines 128 probably proceeds via 2-imino-4-oxoimidazolidine 127(Scheme 40).
The first synthesis of 4-substituted benzenesulfonyl cyanoguanidines 129 (Equation (16))was accomplished by treatment of sodium salt of benzenesulfonamide withN0-substituted-N-cyano-S-methylcarbamidothioates which were obtained by stirring a mixtureof N-cyano-S,S0-dimethylimino carbonate with the desired amine or hydrazine<1996TL7253>.
SN
S
OO
NHR1Cl
Me SN
SH
OO
NHR2
NHR1
Cl
Me
i. H2NNH2 or R2NH2, MeOH, 20 °C
i
125
R1 = alkyl, allyl; R2 = alkyl, NH2
Scheme 39
NH2R1 NH
NH
SPbf
R1 NH
N
NR1R2
PbfR1
O
SO2
i, ii iii
122 123
Pbf =i. Pentafluorophenylchloroformate, DIPEA, DCM
ii. PbfNH2, ButOK, DMSO
iii. R1R2NH, Mukaiyama's reagent, DIPEA, THF, DMF
Scheme 38
Functions Containing an Iminocarbonyl Group 629
N
SCH3R1HN
CN
R2
SO2NH2
N
NH
R1HN
CNO2S
R2
i
129
i. EtOH, NaOH, DMF, reflux
R1, R2 = alkyl
17–82%+
ð16Þ
6.21.1.1.10 N-Aminoiminocarbonyl derivatives
(i) Alkyl and aryl derivatives
In general, N-aminoiminocarbonyl derivatives (N-aminoguanidines) can be prepared followingthe procedures described previously for guanidines, i.e., from the reaction of either hydrazineswith amidinium salts, thioureas, cyanamides, carbodiimides and S-alkyl thioureas, or amines withS-alkylisothiosemicarbazide and N-aminocarbonimidic dichlorides.
No major improvements have been achieved in this area since the publication of chapter6.21.1.1.10 in <1995COFGT(6)639>.
(ii) Imino, nitro, nitroso, and azido derivatives
A wide range of imino and nitro derivatives of guanidines can be obtained using the well-knownBamberger reaction, which consists in the reaction of aryldiazonium salts with nitroalkyl deriva-tives. The use of malonic acid instead of nitroalkyl derivative gives 1,5-diaryl-3-arylazoformazanesvia a 1,5-diarylformazan intermediate.
Although most of the 2-nitrosoguanidines are unstable and decompose to correspondingureas and nitrogen, the 1,1,3,3-tetraphenyl-2-nitrosoguanidine was obtained by nitrosylationof tetraphenyl guanidine and proved to be a stable solid at 20 �C. Alternatively, 3-nitrosofor-mazans could be obtained by the reduction of 1,5-diaryl-3-nitroformazans with H2S<1995COFGT(6)639>.
In recent years, several new methods for the preparation of nitroguanidines have been elabo-rated. Thus, 3,5-dimethyl-N-nitro-1H-pyrazole-1-carboxamidine (DMNPC; 130) has been pre-pared by treatment of 1-amino-2-nitroguanidine with pentane-2,4-dione and then applied forintroducing N-nitroguanidino functions as precursors of guanidino functions <1999JCS(P1)349,1964BBA533>.
The reactions of DMNPC with amines were initially carried out in 1,4-dioxane<1964BBA533>. However, it has been found that better results could be obtained when thereaction is carried out in more polar solvents such as methanol <1999JCS(P1)349>. The useful-ness of DMNPC is exemplified by a facile synthesis of agmatine sulfate 131, as shown inScheme 41. N4-Substituted N1,N8-disubstituted spermidines were obtained analogously. A similarnitroamidination with O-methyl-N-nitroisourea was applied to the synthesis of blastidic acid, acomponent of amino acid in an antibiotic, blasticidin S <2001TL1753>.
HN
H2N NTs
OH2N
R1NH2
HN
NHN
O
Ts
HN
H2N NTs
OR1HN
–NH3
126 127 128
R1 = Me, Et, Pr
Scheme 40
630 Functions Containing an Iminocarbonyl Group
2-Nitro-1-phenylaminoguanidine 133, 2-nitro-1-ureidoguanidine 134, and 1-(2-nitroguanidino)-3-phenylurea 135 were obtained from the reaction of 1-methyl-2-nitro-1-nitrosoguanidine 132 withphenyl hydrazine, semicarbazide, and phenyl carbazide, respectively (Scheme 42). The abovecompounds were further oxidized with bromine to give the corresponding azo-derivatives 136<2000ZOR1615>.
The synthesis of 15N-labeled nitroguanidine 137 was accomplished by treatment of guani-dine sulfate with K15NO3 in concentrated sulfuric acid, as shown in Equation (17). Compound137 was then reduced to 15N-labeled aminoguanidine 138 with zinc powder in acetic acid<2001SC2351>.
NH
H2N NH2
K15NO3
H2SO4
N
H2N NH2
15NO2 Zn N
H2N NH2
15NH2
H2SO4
2
137 138
.ð17Þ
Moderately stable N-pentafluorosulfanyl(perfluoroalkylamino)azidomethine 140 is obtainedfrom the reaction of NaN3 with imine 139 which, in turn, has been obtained by photolysis ofSF5 with N,N-bis-(trifluoromethyl)cyanamide (Scheme 43) <1993IC287>.
CbzHNNH2
.HClCbzHN
HN NNO2
NH2
H3N
HN NH2
NH2SO42–
N
H2N NNO2
N
CH3
H3C
Agmatine sulfate
i ii
131
i. DMNPC, Na2CO3, MeOH, 25 °C, 3 daysii. HCO2H - MeOH, 10% Pd/C, 25 °C, 2 h
130 (DMNPC)
++
Scheme 41
N
NH2NMe
NO
NO2N
NHH2NNHR'
NO2N
NH2N
NO2
NR'
R' NHNH2
H2O, 20 °C
Br2, H2O
0–5 °C
132 133 –135 136
133 R' = Ph
134 R' = CONH2
135 R' = CONHPh
Scheme 42
SF5Cl(CF3)2NCN (CF3)2NCl
N SF5
NaN3(CF3)2N
N3
N SF5
139
hν
140
+ +
Scheme 43
Functions Containing an Iminocarbonyl Group 631
6.21.1.1.11 N�P, N�As, N�Sb, and N�Bi iminocarbonyl derivatives
(i) Phosphorus(III) derivatives
Iminophosphoguanidines 141 (ArN¼P�N¼C(NMe2)2) were obtained by the reaction of imino-chlorophosphines with silylated guanidine. Examples of this class of compounds include tris(tri-chlorophosphoranediylamino)carbenium salts 142 (Figure 3) prepared by the photolysis oftriazidocarbenium hexachloroantimonate in PCl3 <1995COFGT(6)639>.
The chemistry of guanidinylphosphines has recently been developed by Munchenberger andco-workers. Thus, dichloro-N-(N0,N0,N0,N0-tetramethyl)guanidinylphosphine 143 can beobtained by reacting N-trimethylsilyl-N0,N0,N0,N0-tetramethylguanidine (TMSTMG) with PCl3(Scheme 44). The analogous difluorophosphine 144 is prepared from either the reaction offluorochlorophosphine with tetramethyl guanidine (HTMG) <1997PS57> or by treatment oftriphenylmethylphosphonous difluoride with HTMG. The latter reaction involves unusualcleavage of P�C rather than the P�F bond (Scheme 44) <1998EJI865>. On the other hand,dichloro-bis-(pyrrolidinomethyleneimino)-phosphine 145 and dichloro-bis-(piperidinomethyle-neimino)-phosphine 146 are formed upon treatment of lithiated guanidines with PCl3 (Scheme44) <1997PS57>.
From the reaction of HTMG or TMSTMG with dichlorophosphines or chlorophosphines, thecorresponding alkyl(aryl)-bis-[N-(N0,N0,N0,N0-tetramethyl)guanidinyl]phosphines 147 and dialkyl-(aryl)-[N-(N0,N0,N0,N0-tetramethyl)guanidinyl]phosphines 148 were obtained (Scheme 45)<1994PS103>. The compounds 147 were subsequently quaternized at the phosphorus atomupon treatment with MeI at 0 �C.
The substituted guanidinylphosphines 147 and 148 react with Lewis acids, boron trifluoride,and antimony pentachloride to give the phosphonium compounds of type 149 and 150, respec-tively (Scheme 46) <1997PS171>.
Triphenylmethylphosphonous dichloride was found to react with HTMG to give chloro tri-phenylmethylphosphonous N0,N0,N0,N0-tetramethyl guanidine 151. TriphenylmethylphosphonousN0,N0,N0,N0-tetramethyl guanidine 152 was further obtained from the reaction of 151 with LiAlH4
followed by treatment with HCl (Scheme 47) <1998EJI865>.Diphosphine monoxide 154 is formed when the multifunctional 1,2-bis(tritylated)diphosphine
monoxide 153 reacts with HTMG, whereas its tautomer 155 can be obtained from the reaction ofchlorophosphine 151 with triphenyl methylphosphinic acid fluoride (Ph3C-PH(O)F) as shown inScheme 48 <1999ZAAC497>.
N PN
NMe2
NMe2 NN
NCl3P
PCl3
PCl3SbCl6
PMe2N
Me2N N
O
NR2R2N
PEtO
EtO N
X
NR2R2N
141 142
156 157
–
Figure 3
632 Functions Containing an Iminocarbonyl Group
(ii) Phosphorus(V) derivatives
Two major classes of phosphorus(V) derivatives described in <1995COFGT(6)639> comprised(i) guanidinylphosphoric diamides 156 obtained from the reaction of phosphoryl chlorides withguanidines, and (ii) bis-(dialkylamino)methylenephosphoramidic esters 157 generated by thereaction of dichloromethylenephosphoramidic compounds with dialkylamines (Figure 3).
PCl3 P NCl
ClC(NMe2)2
P ClF
FP N
F
FC(NMe2)2 P PPh3
F
F
PCl3 Li+ NN
N
(CH2)n
(CH2)n
PN
N
(CH2)n
(CH2)n
Cl
Cl
i
143
i. TMSTMG, n -hexane, 0 °C to reflux, 2 h
i ii
i. 2HTMG, Et2O, –80 °C to rt, 2 h
ii. HTMG, CHCl3, 25 °C, 1 h
i
144
145, n = 0; 146, n = 1
i. Et2O, 0 °C to rt, 2 h
72%
81%
–
22%
Scheme 44
R1PN
N
C(NMe2)2
C(NMe2)2
PN
N
C(NMe2)2
C(NMe2)2
Me
R1I–
ClPR1
R2NP
R1
R2 C(NMe2)2
R1 R2
A
B
C
Pri Pri
R1PCl2iii
i. 4HTMG, petroleum ether, 0 °C to reflux, 4 h,ii. MeI, Et2O, 0 °C
i
148
147 R1 = Me, But, Ph
Yield (%)
But
74
78
61
i. TMSTMG, petroleum ether, 0 °C to reflux, 3 h
Ph Ph
Ph
+
71 – 75%
Scheme 45
Functions Containing an Iminocarbonyl Group 633
PTrCl
Cl
PTrCl
N C(NMe2)2
PTrH
N C(NMe2)2
Ph3C–
i ii, iii, iv .2HCl
151 152Tr =
i. TMSTMG, toluene, rt, 3 h; ii. LiAlH4, Et2O, 0 °C to rt, 1 h
iii. H2O, rt; iv. toluene, 1 M HCl/Et2O, rt, 71%
84%
Scheme 47
P PTr
Cl O
TrFP P P
Tr
N O
TrF
(Me2N)2C
PTrCl
N C(NMe2)2
PTrH
FO
PTr
N(Me2N)2CO
P FTr
PO
PhCF
H HTMGi
153 154
ii
155151
i. CDCl3, rt, 1 h; ii. Et3N, DCM, rt, 5 h
Et3N, DCM, rt, 2 h
Ph3C–PCl2 +
+
Scheme 48
P N
Ph
Ph
C(NMe2)2 P PPh
PhPh
N
Ph
C(NMe2)2
N C(NMe2)2
F3B
F3B
P NPh
R1
C(NMe2)2 R1 P
Ph
N
Cl
C(NMe2)2
SbCl6
Et2O, –50 °C, 2 h
149
i
150R1 = Ph; 55%
R2 = TMG; 60%
i. 2SbCl5, Et2O, –80 °C, –SbCl3
2BF3.Et2O
+
–
+ –
Scheme 46
634 Functions Containing an Iminocarbonyl Group
Recently, phosphorus pentachloride has been found to react with 2 equiv. of TMSTMG togive bis-N-(N0,N0,N0,N0-tetramethyl)guanidinyltrichlorophosphorane 158 (Equation (18))<1997PS57>.
PCl5 PCl
NCl
NCl
C(NMe2)2
C(NMe2)2
i
i. Et2O, 0 °C, 2 h
2TMSTMG–2MeSiCl
15867%
+
ð18Þ
The phosphorus compounds 147 react readily with sulfur, selenium, and tellurium to give thecorresponding chalogenide derivatives 159 (Scheme 49) <1994PS103>.
As shown in Equation (19), treatment of the chlorophosphonous guanidine 151 with Et3N inH2O gives triphenyl methylphosphonous N0,N0,N0,N0-tetramethyl guanidine 160 <1998EJI865>.
PTrCl
N C(NMe2)2
PTrN C(NMe2)2
OH
Et3N, H2O
151 160
ð19Þ
A series of guanidine-containing phosphorylamides 161–166 have been prepared in the reactionof the appropriate chlorophosphoryl compounds with either HTMG or TMSTMG (Scheme 50). Incontradistinction to guanidinylphosphine 147, the phosphoryl amide 161 undergoes N-alkylationwith methyl iodode to give the ammonium salt 167 <1996ZAAC348>.
The organophosphorus N-(N0,N0,N0,N0-tetramethyl)guanidine fluorides 168(R�P(F)N¼C(NMe2)2; R= t-Bu, Ph) were synthesized and oxidized by sulfur, selenium, and tell-urium as well as by the urea-H2O2 1:1 adduct to give the phosphonic acid derivatives 169–172.Compound 168 (R=Ph) undergoes a Staudinger reaction with triphenylmethyl azide to produce thephosphine imide 173 (Scheme 51) <1996ZN1150>.
A convenient synthesis of thiophosphinyl guanidines 174 has also been described<1995SC2857>. The reaction sequence involves initial preparation of sodium thiophosphinylcyanamide Na[Ph2P(S)NCN] which then reacts with alkyl- and arylammonium chlorides[RNH3]Cl to give the corresponding alkyl- and arylammonium thiophosphinyl cyanamides. Thelatter compounds, when heated at 130–190 �C, rearrange to N-alkyl(aryl)-N0-thiophosphinylguanidines 174 in a Wohler-type reaction (Scheme 52).
PNN
C(NMe2)2
C(NMe2)2
R1
XR1P
NN
C(NMe2)2
C(NMe2)2
R1 X
S
S
S
Se
Te
159
X, i or ii
147
Yield (%) Conditions
78 i
But 86 i
91 i
79 ii
71 ii
i. 1/8 S, toluene, rt, 2 h; ii. Se or Te, rt, 3 days
Me
Ph
Ph
Ph
Scheme 49
Functions Containing an Iminocarbonyl Group 635
PR1
N
F
C(NMe2)2
PR1
N C(NMe2)2
NTr
F
PR1
N C(NMe2)2
OF
PR1
N C(NMe2)2
X
F
TrN3, i
H2O2 /urea, i
X, i
i. Toluene, rt, 2 h
i. 0 °C to rt, 2 h
173
172
169 , X = S; i. toluene, rt, 2–16 h, 73–87%
170 , X = Se; i. toluene, rt to 60 °C, 61–67%
171 , X = Te; i. toluene, rt, 3–16 h, 44–52%
168
87%
63–75%
Scheme 51
PR1
N
R2
O C(NMe2)2
PCl
N
Cl
O C(NMe2)2
PR1
N
Cl
O C(NMe2)2
PR1
N
N
O C(NMe2)2
C(NMe2)2
PN
N
O C(NMe2)2
C(NMe2)2
P
O
N
N(Me2N)2C
(Me2N)2CP
Cl
N
But
O C(NMe2)2 PMe
N
N
O C(NMe2)2
C(NMe2)2
Me
MeI
I
PCl
R1
R2
OP
Cl
R1
Cl
O
PCl
Cl
Cl
OP
Cl
R1
Cl
O
PCl
Cl
O
P
O
Cl
Cl
PBut
Cl
Cl
O
HTMG
R1 = Me
i. TMS
ii.
2 equiv. 2 equiv.
4 equiv.
R1 = Me; R2 = Et2N
R1 = Ph; R2 = Ph
163 162
164
161
R1 = Me, But, Ph
R1 = Ph, Tr
165 166 167
–
Scheme 50
636 Functions Containing an Iminocarbonyl Group
Phosphoryl thiourea 175 can be converted into N1,N1-diphenyl-N3-dialkoxyphosphoryl guani-dine 177 in three steps (Scheme 53). First, the compound 175 is reacted with allyl bromide to giveS-alkenylated product, which upon vacuum distillation in the presence of catalytic amount ofhydroquinone undergoes �-elimination of allyl mercaptan giving rise to the formation ofN-phenyl-N1-dialkoxyphosphoryl carbodiimide 176 in 50% yield. The final product 177 isobtained by reacting 176 with aniline at room temperature <1994ZOB931>.
(iii) As, Sb, and Bi derivatives
The only report mentioned in <1995COFGT(6)639> referred to dative-bonded complexes ofguanidines and bismuth or antimony trihalides.
In 1994 a reaction of TMSTMG with MeAsCl2 leading to methyl [N-(N0,N0,N0,N0-tetramethyl)-guanidinyl]chloroarsine 178 was described (Equation (20)) <1994PS103>.
MeAsCl2 NAsCl
MeC(NMe2)2
TMSTMG, rt, 2 h
–Me3SiCl
178
ð20Þ
An interesting complex between antimony(III) and guanidine is also described <1997CC1161>.1,2,3-Triisopropyl guanidine reacts with antimony tris(dimethylamide) (Sb(NMe2)3) to givecomplex 179 in which the Sb is chelated by a [C(N�Pri)3]2� dianion and a [iPrN)2CNHPri]�
monoanion (Equation (21)).
Ph2PCl
SNa2NCN Na Ph2P
NCN
SPh2P
NCN
S
Ph2PN
S
CNH2
NHR1
R1NH3 Cl-
R1NH3
130–190 °C
174
R1 = Bun, But, c -hexane, Ph, p-ClC6H4
+ ++
+– – –
Scheme 52
(PriO)2PO
NH
S
NHPh (PriO)2PO
N
S
NHPh
Br
SH
(PriO)2PO
NC
NPhNH2
(PriO)2PO
N NHPh
NHPh
, Et3N
-
∆, 0.05 mmHg
rt
175
176 177
Scheme 53
Functions Containing an Iminocarbonyl Group 637
C NPri
PriHN
PriHN Sb(NMe2)3PriN
N
N
Pri
Pri
Sb NHPriN–
N
Pri
Pri
2–3
179
+
ð21Þ
6.21.1.1.12 N�Si, N�Ge, and N�B iminocarbonyl derivatives
According to chapter 6.21.1.1.12 in <1995COFGT(6)639>, N-silylated guanidines 180 (Figure 4)and guanidinium salts [Me2N)2CHTMS]+ Hal� were prepared by reacting the correspondingguanidine with a chlorosilane in the presence of a base and in the absence of added base,respectively.
N-Borated guanidines were represented by triarylboron complexes 181 (Figure 4) and noN-germylated guanidine derivatives were described in <1995COFGT(6)639>.
Recently, N-silyl-N0,N0,N0,N0-tetramethyl guanidine (TMSTMG) was applied to the synthesis of2-azonioallene salts of type 182 (Equation (22)) <1989S400>.
Cl
Me2N NMe2
SbCl6–
NSiMe3
Me2N NMe2
NNMe2
NMe2Me2N
Me2NSbCl6
–i
–Me3SiCl
i. 1,2-dichloroethene, –50 °C to –20 °C 23 °C, 5 h
18278%
+
+ ð22Þ
A new class of Si�N bonded compounds 183 was obtained from the reaction of biguanide andits N-alkyl derivatives with diorganosilanes R1R2SiNH2 (R1,R2=Ph; R1=Me, R2=Ph)<2001JCS(D)1582>. The reaction proceeds via SiH/NH dehydrocoupling and affords corre-sponding oligomeric 1,4-bis-(silyl)biguanides (Equation (23)).
H2N N NHR3
NH NH2
HN N N
NH NH
Si
Si
HR3R1
R2H
R2H R1
R1R2SiNH2
THF, reflux, 16 h
R3 = H, Pr, cyclohexyln
183
ð23Þ
Guanidinate anions of type 184 are generated by the reaction of lithium bis(trimethylsilyl)amide(LiN(SiMe3)2) with 1,3-alkyl carbodiimides (R1,R2= iPr, cyclohexyl) (Scheme 54). Lithium salts184 were isolated in pure form and used for preparation of a series of bis- and monoguanidinatecomplexes of Zr and Hf <1999IC5788>, Nb and Ta <1999POL2885>, as well as Yb and Sm<1998OM4387>.
As depicted in Equation (24), the [2+2] cycloadditions that take place between imidozircocenecomplexes and 1,3-di-(trimethylsilyl)carbodiimide give other types of diazametallacycle complexes185 <2001OM1792>.
NNMe2
NMe2TMSN
NHR
NHRAr3B–
H
180 181
+
Figure 4
638 Functions Containing an Iminocarbonyl Group
CMe3SiN NSiMe3
Cp2Zr NBut NBut
NSiMe3
C NSiMe3Zr
185
ð24Þ
6.21.1.2 Iminocarbonyl Derivatives with One Nitrogen and One P, As, Sb, or Bi Function
6.21.1.2.1 N-Alkylimino derivatives with one P or As function
Title compounds 186 (Figure 5) were usually obtained by Michaelis–Arbuzov reaction ofthe carbamimidic chlorides with trimethyl phosphite (P(OMe)3). Another method for prepara-tion of 187 consists in the attack of alkali metal organoarsenides at N,N0-dialkyl carbodiimidesfollowed by hydrolysis or alkylation of the intermediary formed (lithioamidino)arsines<1995COFGT(6)639>.
Recently, the phospha(III)guanidine compounds of the general formula Ph2PC(NR)(NHR);R=Pri, cyclohexyl) have been prepared in good yields as described in Scheme 55.Lithium diphenylphosphide obtained by treatment of Ph2PH with BuLi is allowed to react withsuitable carbodiimide giving the corresponding lithium phospha(III)guanidinate. Quenching thereaction with triethylamine hydrochloride yields the neutral phospha(III)guanidines 188<2002CC2794, 2003JCS(D)2573>.
N
N N
SiMe3Me3Si
R2R1
Li
N
N N
SiMe3Me3Si
R2R1
R1N=C=NR2
Et2O, rt, 4 h
184
M(X)n
M(X)n
(Me3Si)2N– Li+ +
Scheme 54
RNP
MeOOMe
O
CO2EtBun
R'NAsR2
2
NR'R3ArN
P(OR1)2
NR2R3
O
PhNP(OEt)2
N
O
CF3
Ph PhNN(Ph)R3
PR1R2RO N P(OR)2
O NEt
O
186 187 189
190 191 195
Figure 5
Functions Containing an Iminocarbonyl Group 639
6.21.1.2.2 N-Arylimino derivatives with one P function
There are three methods described in <1999COFGT(6)639> for the preparation of amidino-phosphonates of type 189 (Figure 5). The first involves the reversible reaction of N,N0-diphenylcarbodiimide with a phosphite triester. The second method consists in the direct aminolysis ofiminochlorides of general formula ArN=C(Cl)P(O) (OR1)2. The third method is based on aMichaelis–Arbuzov reaction of the amidinochlorides with trialkyl phosphites. When a chloroalkyl-carbodiimide was used instead of carbodiimide in a variant of a Michaelis–Arbuzov reaction, thecorresponding alkylideneamidophosphonate 190 could be obtained.
Amidinophosphines 191 (Figure 5) are usually prepared by the addition of phosphinescontaining PH or PSi bond across the C¼N bond of carbodiimide. Thus, the reaction ofmonophenylphosphine (PhPH2) with carbodiimide gives the bis(amidino)phosphine and analo-gous reaction of carbodiimide with diphenylphosphine (Ph2PH) leads to the formation ofmono(amidino)phosphine <1995COFGT(6)639>.
In 1995 Komalov and co-workers described a facile synthesis of novel dialkyl-N-arylimino(amidino)phosphonates 192 <1995ZOB46>. The addition of anilidophosphines to car-bodiimides carried out at room temperature afforded the compounds 192 in 87–97% yield(Equation (25)).
P NHR2R1O
R1OR1O P
NR2
OR1 NR3
NHR3
R3N=C=NR3
R1 = Et, Pri; R2 = Ph, Tol; R3 = Ph, cyclohexyl
192
+
ð25Þ
The C-phosphorylated N,N-dimethyl-N0-tolyl formamidines 194 are obtained starting fromN,N-dimethyl-N0-tolyl formamidines, which reacts with PBr3 to give the dibromophosphine 193.The above reaction represents the first example of electrophilic substitution at a formamidinecarbon atom. Then, the intermediate 193 upon treatment with dialkylamine and elemental sulfuris converted into the desired C-phosphorylated amidines 194 in 40–44% yields (Scheme 56)<1996ZOB1930>.
6.21.1.2.3 N-Acylimino derivatives with one P function
N-Acylimino derivatives are usually generated from dichloromethyl isocyanate precursors bearingthe dichlorophosphine moiety. First, in the reaction with alcohols they are converted to chloro-imines, which, on treatment with diethylamine, give the N-acyliminoamidinophosphonates 195(Figure 5).
No major progress has been made since the publication of <1995COFGT(6)639>.
Ph2PH Ph2PNR1
NHR1N
NP
R1 Li
LiN
N
R1
PPh
Ph
R1
Ph
Ph
R1
i, ii iii
R1 = Pri, cyclohexyl
i. BuLi in hexanes, THF, 0 °C, 0.5 h ii. Carbodiimide, THF, 0 °C to rt, overnightiii. Dry [HNEt3][Cl], THF, rt, 1 h
188
71%
Scheme 55
640 Functions Containing an Iminocarbonyl Group
6.21.1.2.4 N-Haloiminocarbonyl derivatives with one P function
Phosphorylnitrile oxide generated in situ from the corresponding hydroxamic acid chloride iseasily converted into phosphorylamidoxime 196 upon treatment with aliphatic and aromaticamines, benzhydrazide, or semicarbazide (Scheme 57). The reactions are carried out at roomtemperature or at reflux for 5min in solvents such as chloroform and acetonitrile. In the case ofsemicarbazide the hydroxamic acid chloride is treated with KOH in PriOH <1995ZOB1991>.
6.21.1.2.5 Hydrazono derivatives with one P function
N0-Aryl-C-(dialkoxyphosphoryl)formamidrazones (197; X=NMe2) (Figure 6) were obtainedfrom the reaction of corresponding chlorohydrazono derivatives with aqueous solution of aminesor phenylhydrazine. Similarly were obtained the azido and nitrohydrazones (197; X=N3, NO2).
The 1,3-addition of mono- or dialkylamines to nitrile imines (Ar2P�N��N+�C�P(S)(NR1R2)2) furnished N0-phosphineformamidrazones 198 (Figure 6).
(Arylhydrazono)arylazomethyl)phosphonates 199 (Figure 6) were obtained by couplingreaction of phosphinyl acetaldehyde with diazonium salts. Alternatively, the coupling reactionof the triphenylphosphine acetic acid with 2molar equiv. of diazonium salt furnished thebis(arylazo)methylenephosphine 200 (Figure 6).
Oxidation of the dialkoxyphosphorylamidrazone with silver(I) oxide gave the N-(arylazo)dialk-oxyphosphoryl)methyleneamine 201 (Figure 6).
No further advances have occurred in this area since the publication of chapter 6.21.1.2.4 in<1995COFGT(6)639>.
6.21.1.2.6 Diazonium derivatives with one P function
Title diazomethane derivatives 202 (Figure 7) are usually obtained by the treatment of diazo-methylphosphonates with dinitrogen pentoxide (N2O5).
Since the publication of chapter 6.21.1.2.5 in <1995COFGT(6)639> no further advances haveoccurred in this area.
(PriO)2PO
Cl
NOH (PriO)2PO
CN
O
(PriO)2PO
NHR1
NOHR1NH2
196
R1 = Bu, Ph, 4-NH2C6H4, 4-O2NC6H4, NHC(O)NH2, NHC(O)Ph
Scheme 57
NMeN
Me
Me PBr3NMe
NMe
Me
Br2P
NMeN
Me
Me
(R1R2N)2PS
Pyr
Et3N, 0 °C
193
i. R1R2NH
ii. 1/8 S, rt, 8 h
R1, R2 = Me, Et
194
+
Scheme 56
Functions Containing an Iminocarbonyl Group 641
6.21.1.2.7 N,N-Dialkyliminium derivatives with one P function
In chapter 6.21.1.2.6 in <1995COFGT(6)639> the following methods were described for prepar-ing the title compounds.
For the syntheses of phosphaallylic salts and phosphorylated amidinium salts,N,N,N0,N0-tetramethylimidoyl chloride is used as starting material: (i) it reacts with0.5 molar equiv. of tris(TMS)phosphane (P(TMS)3) to give compounds 203 (Figure 7);(ii) upon treatment with triethyl phosphite the monophosphorylated amidinium salts 204 areobtained; and (iii) it undergoes a standard Michaelis–Arbuzov reaction with alkyl diphenylphos-phinite having only one displaceable alkyl group to give the salt 205.
Although the majority of phosphaalkenes show a polarity P�+C�� of P¼C double bond, in anumber of P-acyl, P-dithiocarboxyl, and P-thiocarbamoyl-phosphaalkenes, an inverse polarityP��C�+ of the multiple bond is observed. Recently, the synthesis, structure, bonding, andcoordination chemistry of these derivatives have been investigated in detail <1998OM3593>.Replacement of the P-silyl group in P-trimethylsilyl-substituted phosphoalkanes 206 by acyl,dithiocarboxy, and thiocarbamoyl functions leads to the compounds 207, 210, and 211, respec-tively (Scheme 58). Based on a significant deshielding of the 31P NMR resonances and X-raystructure analysis, the electronic configuration was described by canonical formulas 207, 208, and209 (Scheme 58). X-ray structure analysis of 210 confirmed the existence of multiple bonding ofplanar carbenium center (C5) to the planarly configured atoms C(2)�N(1) and C(2)�N(3).
Reactivity of the carbonyl-functionalized phosphaalkanes 207 toward protic acids, Lewis acids,and alkylating and silylating agents were investigated by Weber and co-workers <1999EJI2369>. Itwas found that the reaction with protic acids and alkylating agents occurred at two-coordinatephosphorus atom yielding the phosphanyl-substituted amidinium cations 212 and 213. Silylationwith Me3SiOSO2CF3 resulted in the attack at the oxygen atom (formation of 214). Also Lewis acidB(C6F5)3 was ligated at the oxygen atom of carbonyl group to give the adduct 215 (Scheme 59).
The structures of the adducts of 207 with the homologous Lewis acids AlMe3, GaMe3, andInMe3 were also investigated in detail. AlMe3 was ligated to the oxygen atom of the carbonyl
N2
NO2
PO
R1
R2
R22N
NR22
NR22
NR22
NR22 NR2
2
PX–
R22N
POEt
OEt
O
R22N
PPh
Ph
O
202 203 204 205
+ + +
Figure 7
ArHNN R2
O
XR1
HN N NPri
S
NPri
NPri
P PAr
Ar
NN=NAr
P(OR)2
O
ArHN
N
N=NAr
PPh3
ArHN
BF4– RN
N=NAr
P(OR1)2
O
197
X = NMe2, N3, NO2
198199
200 201
P
+
2
2
2
Figure 6
642 Functions Containing an Iminocarbonyl Group
group; 2molar equiv. of GaMe3 were added to the oxygen and phosphorus atom, and InMe3 wasbound to the phosphorus center of the phosphaalkane (Scheme 60) <1999EJI2369>.
Molecules of type 210 and 211 were found to behave as multidentate ligands in transition metalchemistry (Equation (26)). Thus, they reacted with (CO)5MBr (M=Mn, Re) to afford tricycliccomplexes 216 and 217 <1998OM3593>. Complexation of 207 with transition metal carbonylstook place at the pnictogen atom resulting in the complexes of type 218 (RC(O)P[M(CO)n]C(NMe2)2)(R= t-Bu, Ph; M=Ni, n=3; Fe, n=4; Cr, n=5) (Equation (27)).
Me3SiPNMe2
NMe2 CS2
PhNCS
PNMe2
NMe2
OR1
PNMe2
NMe2
R1
OP
NMe2
NMe2
R1
O
208
PNMe2
NMe2
SMe3SiS
PNMe2
NMe2
SN
Me3Si
Ph
R1COCl
207
209
210206
211
+ +
––
Scheme 58
PNMe2
NMe2
R1
OP
NMe2
NMe2
R1
OSiMe3
PNMe2
NMe2
R1
O(C6F5)3B
Me3SiSO2CF3
PNMe2
NMe2
R1
O Me
CH3OSO2CF3
PNMe2
NMe2
H
R1
O
BF –
214
213
212
HBF4/Et2O
215
207
SO3CF3–
SO3CF3–
+
+
+
+
Scheme 59
Functions Containing an Iminocarbonyl Group 643
(CO)5MBr X
P
S
Me2N
Me2N
MP
M
L
L
L
SX
L
LL
NMe2
NMe2
210, 211–Me3SiBr, – 4CO
L = CO, M = Mn, Re; 216 , X = S; 217 , X = NPh
ð26Þ
PNMe2
NMe2
R1
OP
NMe2
NMe2
R1
O
M(CO)4
207 218
+
ð27Þ
6.21.1.3 Iminocarbonyl Derivatives with One Nitrogen and One Metalloid Function
6.21.1.3.1 Silicon derivatives
A compound of this class, silanecarboximidamide 219 (Figure 8), was prepared by the reactionof N,N0-diphenyl carbodiimide and bis(TMS)mercury <1995COFGT(6)639>.
Since the publication of chapter 6.21.1.3.1 in <1995COFGT(6)639> no further advances haveoccurred in this area.
PNMe2
NMe2
R1
OP
NMe2
NMe2
R1
OInMe3
InMe3
PNMe2
NMe2
R1
OAlMe3
AlMe3
PNMe2
NMe2
R1
OGaMe3
Me3Ga
207
2GaMe3
+
+
+
–
–
–
Scheme 60
PhNN(Ph)TMS
TMS
N
BN
R2 R1
R4R4
PhN R3R1N
NMe2
BR22
N
B NH
PhN
BuBu
219 221220 222
++–
–
Figure 8
644 Functions Containing an Iminocarbonyl Group
6.21.1.3.2 Boron derivatives
N-Alkylboranecarboximidamide 220 (Figure 8) is formed as a by-product of the reaction of�-lithio-N,N-dimethylacetamide with bromodimethylborane. Other examples of borane carbox-imidamides 221 and 222 can be prepared by reacting phenyl isocyanide with boraneamide and2-(dialkylboryl)aminopyridine, respectively <1995COFGT(6)639>.
Recently, novel types of [amine-bis-(amidinium) hydroboron2+] 225 and [amine-bis(triethyl-amidinium)hydroboron2+] 226 cations have been obtained <1999IC5250>. First, the cyanogroups of 223 are activated by ethylation employing Et3OBF4 to give [amine-bis(ethylnitrilium)-hydroboron2+] tetrafluoroborates 224. Then, nucleophilic addition of ammonia and diethylaminegives 225 and 226, respectively (Scheme 61).
6.21.1.4 Iminocarbonyl Derivatives with One Nitrogen and One Metal Function
6.21.1.4.1 Main metal derivatives
The trialkylstannyl and trialkylplumbyl formamidines 227 (Figure 9) were obtained by the1,1-addition of a metal amide to an aryl isocyanide <1995COFGT(6)639>.
Adducts of InMe3 with aryl isocyanides of general structure Me3InCNR (228, R=4-MeC6H4,4-OMeC6H4) react slowly at room temperature with pyrrolidine to give the insertion products 229(Scheme 62). The same compounds were obtained by reacting InMe2Pyrr 230 with correspondingisocyanides <2001JOM11>.
6.21.1.4.2 Transition metal derivatives
The nucleophilic attack of azetidine at the carbon atom of coordinated isocyanide ligands of theneutral or cationic complexes of Pd and Pt resulted in the formation of the diaminocarbenecomplexes 231 and 232, respectively (Figure 9).
The reaction of tetrakis(t-butyl isocyanide)rhodium(I) tetrafluoroborate with dimethylamineand diethylamine gave 1:1 adducts 233 containing a �-bonded amidinium cation<1995COFGT(6)639>.
A HBCN
CNA HB
C
C N
N
Et
EtA HB
C
C NHEt
NHEt
H2N
H2N
A HBC
C NHEt
NHEt
Et2N
Et2N
2PF6–
DCM, reflux, 25 h
2+
223 224
i
2+
225
ii
2+
226
i. Liquid NH3, –30 °C, 5 minii. Et2NH, rt, 5–10 min, then H2O, NaPF6
Et3OBF42BF4
– 2BF4–
Scheme 61
Functions Containing an Iminocarbonyl Group 645
Pentacarbonyl {(dimethylamino)[methoxy(phenyl)methyleneamino]carbene} complexes of molyb-denium(0) and tungsten(0) 234 react with chloroauric acid to give chloro{(dimethylamino)[methoxy(phenyl)methyleneamino]carbene}gold(I) 235 and trichloro{(dimethylamino)[methoxy(phenyl)methyleneamino]carbene}gold(I) 236 (Scheme 63)<1981CB3412, 1981AG(E)461>. Compounds 235 and 236 react with boron tribromide to give thetribromo derivative 237, which, in turn, is converted into triiodo gold complex 238 upon treatmentwith boron triiodide <1985JOM279>.
InMe3 Me3InCNRMe3In
NR
N Me2In NRNC, i ii iii
i. n-Hexane, rt, 24 h
ii. Pyrrolidine, n-hexane, rt, 33 days
iii. RNC, n-hexane, rt, 2 months
229228 230
+
Scheme 62
ArNNR2
2
MR13
NNHR
M(PPh3)Cl2
NHN
M(PPh3)Cl
OMeBF4 Rh(C
ButHN
R2N
227
M = Sn, Ar = 4-MeC6H4, R1 = R2 = Me
M = Pb, Ar = Ph, R1 = Bu, R2 = Et
231
232
M = Pd, Pt
NBut)3 BF4
233
+
+
– –
Figure 9
(CO)5M
NMe2
NOMe
PhHAuCl4
ClAu
NMe2
NOMe
Ph Cl3Au
NMe2
NOMe
PhPBr3
Br3Au
NMe2
NOMe
PhBI3 I3Au
NMe2
NOMe
Ph
M = Mo(II), W(III) 235 236
237 238
234
+
Scheme 63
646 Functions Containing an Iminocarbonyl Group
Isocyanide complex [AuCl(C�NBut)] 239 reacts with terminal alkynes in diethylamine togive the corresponding alkynyl(carbene) complexes 240 and 241 (Scheme 64)<1997OM5628>.
As shown in Equation (28), the insertion reaction of aryl isocyanides with zirconium amido silylcomplex leading to the compound 242 has recently been described <1999OM1002>.
ZrSi(SiMe3)3
Me2N NMe2
NMe2
ArNCZrSi(SiMe3)3Me2N
NMe2Me2N
Ar
N
Zr
Ar NMe2
NMe2
Si(SiMe3)3Me2N
242
Ar = 2,6-Me2C6H3
CN
ð28Þ
The carbodiimide complex 244 and the four-membered metallacycles 245 are obtained from thereaction of the isocyanide metal precursors (243, M=Co, Rh) with aryl azides (Scheme 65). Asevidenced by NMR spectroscopy, the compound 245 exists in equilibrium with isomer 246<1998JOM(551)367>.
6.21.2 IMINOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE P, As,Sb, OR Bi FUNCTION (AND NO HALOGEN, CHALCOGEN, OR NITROGENFUNCTIONS)
6.21.2.1 Iminocarbonyl Derivatives with One P, As, Sb, or Bi Function andOne P, As, Sb, or Bi Function
6.21.2.1.1 Bis(phosphino)iminocarbonyl derivatives
Phosphorus compounds of type 247 (Figure 10) in which the carbon atom of the iminocarbo-nyl group is attached to two three-valent phosphorus atoms were found to be unstable, and,therefore, little is known about their properties. The more stable (diazomethylene)-bis(phospho-nous diamides) 248 were obtained by addition of the lithium salt of the bis(phosphanyl)diazo-methane to the chlorophosphane <1995COFGT(6)639>.
[Bis(diisopropylamino)phosphonio][chloro(isopropylamino)phosphino]diazomethane 249 isreadily available by addition of the lithium salt of [bis(diisopropylamino)phosphino]diazomethaneto dichloro(isopropylamino)phosphane (Equation (29)) <2000AG(E)3319>. Interestingly,
NBut]
AuNHBut
NEt2CRC
AuEt2N
ButHNC C(CH2)5C C Au
NHBut
NEt2
CHRC
HC C(CH2)C CH, Et2NH, rt,14 h
[AuCl(C
i
ii
240 R = H, But, SiMe3
241
, Et2NH, rt, 17–24 h i.
ii.
239
Scheme 64
Functions Containing an Iminocarbonyl Group 647
(phosphino-(P-chlorophosphonio)diazo derivative 252, obtained by addition ofbis(diisopropylamino)phosphonium salt 250 to P-chlorodiazomethylenephosphorane 251 at–30 �C, appeared to be unstable with respect to dinitrogen elimination, which began at �23 �Cand led to the corresponding carbene 253 (Scheme 66) <1996IC46>.
P CR
R N2
LiRPCl2 P C
R
R N2
PR
Cl
i
R = Pri2N
i. THF, –78 to 0 °C, 1 h
249
+
ð29Þ
ArNP
P
PhTMS
TMSPh
N2
P(NR2)2
P(NR2)2
247 248
Figure 10
MCNRMe3P
ArN3 MNArMe3P
RN
MCMe3P
NRNAr
NR
CoCMe3P
NH11C6NPh
NC6H11 CoCMe3P
NPhNC6H11
NC6H11
Co CNC6H11Me3P
NPhH11C6N
246
–N2
M = Co, Rh; Ar = Ph, Tol; R1 = C6H11, bn
243 244 245
245
+
+
+
Scheme 65
P C N2
Cl
RR C
N2
P PR
ClR
R
R
CP P
R
ClR
R
R–33 °C
250 251 252
–N2
>–23 °C
253
R = Pr2i N
R2P+ TfO–++
Scheme 66
648 Functions Containing an Iminocarbonyl Group
Diphosphirenium salt 254 reacts with t-butyl isocyanide at �50 �C to give four-memberedheterocycle 255 featuring a �3�2-phosphorus–carbon double bond <1994CC337>. The lattercompound upon treatment with nucleophiles such as butyl- or methyllithium forms a phosphorusheterocycle 256 (Scheme 67).
Alkyl and aryl isocyanides are able to cleave the P¼P bond in the metallodiphosphenes oftype 257 to give either the 3-diphosphiranimine 258 or 2,4-diimino-1,3-diphosphetanes 259(Scheme 68) <1994OM4406, 1995ZAAC1407, 1998JFC73>.
6.21.2.1.2 Bis(phosphinyl)iminocarbonyl derivatives
This class of compounds containing five-valent phosphorus atoms includes diphenyl-, dialkoxy-,diamino-, alkoxyamino-, and alkoxyfluoro-phosphinyl derivatives, all of which can be synthesizedaccording to the following methods <1995COFGT(6)639>.
(a) From carbonimidic dichlorides and organophosphorus reagents, such as (RO)2P(O)Rand Ph2P(O)(OR), were obtained (arylcarbonimidoyl)bisphosphonic acid esters 260,bis(diphenylphosphinyl)methylene)arylamines 261, respectively (Figure 11). Analogously, theMichaelis–Arbuzov reaction of phenylsulfonylcarbonimidic dichloride with (RO)3P gives deriva-tives 262.
(b) From carbimidic dichlorides by metal–halogen exchange with Me2TlP(O)Ph2 the com-pounds 261 are produced (Figure 11).
(c) (Diazomethylene)bisphosphonates 263 are prepared by treatment of the correspondingC�H active methylene precursor with tosyl azide in the presence of potassium t-butoxide.
(d) Reaction of the lithium salt of the thioxophosphoranyldiazomethane with chlorophosphanederivatives leads to the phosphinothioyl compounds 264 (Figure 11).
(e) P,P0-(carbonimidoyl)bis(phosphonic amide) 265 is obtained from the reaction of phos-phorus(III) acid anhydride with an aryl isocyanate (Figure 11).
P P
NR2
NR2
NR2
P P
NR2
NR2
NR2C
NBut
BF4–
P P
NR2
NR2
NR2CN
But BF4–
R1P P
NR2
NR2
NR2CN
ButBF4–
But–NC
–50 °C
R1–Li
254 255 256
R = Pri; R1 = Me, Bu
+
+
+
Scheme 67
RNCP P R2R1
PPR1 R2
NR
P P
N
N
R
R
R2R1RNC
258 259
R = Ph, 2-MeC6H4
R1 = cp*(CO)2Fe, C(SiMe3)3
R2 = C(SiMe3)3
R = C6H11, bn
R1 = cp*(CO)2Fe
R2 = 2,4,6-ButC6H2
257
3
Scheme 68
Functions Containing an Iminocarbonyl Group 649
6.21.2.1.3 Iminocarbonyl derivatives with P function and one P, As, Sb, or Bi function
Since the publication of chapter 6.21.2.1.1 <1995COFGT(6)639> no major advances haveoccurred in this area.
6.21.2.1.4 Iminocarbonyl derivatives with one As, Sb, or Bi functionand another As, Sb, or Bi function
The bis(3-valent) organometallic diazomethanes depicted in Figure 12 as 266 were prepared bytreating the arsino-, stibino-, or bismuthino-dimethylamides with diazomethane. From two-stepreactions of this type, mixed organometallic derivatives were also obtained.
No advances have occurred in this area since the publication of chapter 6.21.2.1.2<1995COFGT(6)639>.
6.21.2.2 Iminocarbonyl Derivatives with One P, As, Sb, or Bi Functionand One Si, Ge, or B Function
6.21.2.2.1 Iminocarbonyl derivatives with one P function and one Si, Ge, or B function
(i) Silicon derivatives
Thewell-known compounds in this class are phosphorus-containing silyldiazomethane derivatives 267(Figure 13). Dialkylphosphanylsilyldiazomethanes (X= lone pair, R1,R2,R3Si=TMS,R4=R5=But), dialkylaminophosphanylsilyldiazomethanes (X= lone pair, R1,R2,R3Si=TMS,R4, R5=dialkylamino) were prepared by reacting the lithium salt of the(trimethylsilyl)diazomethane with the desired chlorophosphanes. However, silylated �-diazo phos-phonates (X=O, R1,R2,R3Si=TMS, TBDMS, SiPri3, R
4,R5=OMe, OEt) and phosphonothioic
ArNP(O)(OEt)2
P(O)(OEt)2
ArNP(O)Ph2
P(O)Ph2
PhSO2NP(O)(OR)2
P(O)(OR)2
N2
P(X)R2
P(X)R2
N2
P(S)R22
P(S)R21
PhNP(O)(NEt2)2
P(O)(NEt2)2
260 261 262
263 264 265
R1 = Ph, NMe2, NPri2
R2 = But, NPri2
X = O, SR = OMe, OEt, Ph
Figure 11
N2
MMe2
MMe2
266 M = As, Sb, Bi
Figure 12
650 Functions Containing an Iminocarbonyl Group
diamides (X=S, R1,R2,R3=TMS, SiPh3, R4,R5=NPri2) could be obtained by reacting lithiated �-
diazo phosphonates with corresponding silyl electrophiles (chlorides or triflates). �-Diazo phosphinesulfides (X=S, R1,R2,R3Si=TMS, R4,R5=But) and �-diazo phosphonothioic diamides (X=S,R1,R2,R3=TMS, R4,R5=NPri2) were obtained by direct sulfurization of the corresponding phos-phanyl precursors <1995COFGT(6)639>.
(ii) Germanium derivatives
Insertion reaction of phenyl isocyanide into the weak Ge�P bond of germanylphosphine(Et3GePEt2) led to the formation of triethylgermanium derivative 268 (Figure 13). The�-diazo phosphonothioic diamide triethylgermanium compound 269 was obtained by reactinglithiated �-diazo phosphonate with trialkylgermanium chloride <1995COFGT(6)639>.
(iii) Boron derivatives
The only examples of this class are internal salts 270 (R=H, F) which can be prepared byoxidative ylidation of the �-diazophosphane 267 (X= lone pair, R1,R2,R3Si=TMS,R4,R5=NPri2) with CCl4 followed by reaction with boron-containing Lewis acids (BH3 or BF3)(Figure 13) <1995COFGT(6)639>.
Since the publication of chapter 6.21.2.2.1 <1995COFGT(6)639> no new synthetic methodsfor these classes of iminocarbonyl derivatives have been described.
6.21.2.2.2 Iminocarbonyl derivatives with one As, Sb, or Bi function and one Si, Ge, or B function
The reaction of (TMS)diazomethanes (M1=Si) with metal amides (M2=As, Sb, Bi, R=Me,n=3) leads to the formation of the corresponding (�-diazo(TMS)methyl)dimethyl arsines,stibines, and bismuthines 271 (Figure 13). (Diazotrimethylgermanylmethyl)dimethylarsine(M1=Ge, M2=As, R=Me, n=3) can be prepared similarly <1995COFGT(6)639>.
No new synthetic methods for these classes of iminocarbonyl derivatives have been describedsince the publication of chapter 6.21.2.2.2 <1995COFGT(6)639>.
N2
P(X)R4R5
SiR1R2R3
PhNGeEt3
PEt2
N2
P(NPr2)2i
GeEt3
S
N2
P(NPr2)2i
BR3
Cl
N2
M1Me3
M2Me3
267
R1R2R3Si = TMS, TBDMS, SiPri3, SiPh3
R4, R5 = alkyl, dialkylamino, OMe, OEt
X = lone pair, O, S
268 269
270 271
M1 = Si, Ge
M2 = As, Sb, Bi–
+
Figure 13
Functions Containing an Iminocarbonyl Group 651
6.21.2.3 Iminocarbonyl Derivatives with One P, As, Sb, and Bi Function and One Metal Function
6.21.2.3.1 Iminocarbonyl derivatives with one P function and one metal function
(i) Main group metals
Metallation of the phosphinodiazomethane derivatives with BuLi gives corresponding lithiumsalts 272 (Figure 14). Treating the diazolithium salt 272 with trimethylchlorostannane providesthe diazomethylstannyl compound 273 <1995COFGT(6)639>.
In 1995, from the reaction of lithium salt of [bis(diisopropylamino)phosphine]diazomethanewith triphenyl- and tricyclohexylchlorostannane, the diazo derivatives 274 were obtained<1995TL4231>. Photolysis of these compounds in the presence of t-butyl isocyanide affordedketene imines 275 as depicted in Scheme 69. The reaction proceeds via rather unstable(phosphino) (stannyl)carbene which can be trapped by t-butyl isocyanide. Compounds 275 caneasily be isolated after treatment with elemental sulfur, as the compounds 276 in 86–88% yield.
(ii) Transition metals
Metallation of the phosphinediazomethane derivatives with Ag2O or Ag(acac) and HgO or Hg(acac)2led to the formation of diazomethylsilver (277, R1=R2=OMe, OEt, R1=OMe, R2=Ph) andbis-(diazomethyl)mercury, respectively (278, R1,R2=OMe, OEt, Ph) (Figure 14)<1995COFGT(6)639>.
No new synthetic methods for this class of iminocarbonyl derivatives have been described sincethe publication of chapter 6.21.2.3.1 in <1995COFGT(6)639>.
N2
P(X)R1R2
LiN2
P(X)(NPr2)2i
SnMe3
N2
P(O)R1R2
HgN2
P(O)R1R2
N2
P(O)R1R2
Ag
N2
AsMe2
MMe3
N2
AsMe2
HgN2
AsMe2
272 273
X = O, lone pair
R1, R2 = But, NPr2i
277
278 279 M = Sn 280 M = Pb
281
Figure 14
N2SnR1
3
PR2
R2P C SnR13
But–NCN
R2P
R13Sn But
S8
NR2P
R13Sn But
Shν
274 275 276R = Pri2N; R1 = Ph, cyclohexyl
Scheme 69
652 Functions Containing an Iminocarbonyl Group
6.21.2.3.2 Iminocarbonyl derivatives with one As, Sb, and Bi function and one metal function
Metallation of diazomethylarsines with metal amides Me3SnMe2 and Me3PbN(TMS)2 providesthe corresponding derivatives 279 and 280 with trimethylstannyl and trimethylplumbyl substitu-ents, respectively (Figure 14). Similarly, using Hg(N(TMS)2)2 as metallating agent,bis-(diazo(dimethylarsino)methyl)mercury 281 is obtained <1995COFGT(6)639>.
Since the publication of chapter 6.21.2.3.2 in <1995COFGT(6)639> no advances haveoccurred in this area.
6.21.2.3.3 N-Unsubstituted iminocarbonyl derivatives
Although the electronic structure of HN=C(TMS)2 has been calculated, synthetic method for thisclass of iminocarbonyl derivatives is not reported <1995COFGT(6)639>.
6.21.2.3.4 N-Alkyl- and N-aryliminocarbonyl derivatives
There were two general methods described in chapter 6.21.3.1.2 in <1995COFGT(6)639>. Firstone, consisting in the insertion reaction of alkyl or aryl isocyanides into metal–metal bonds. TheN-cyclohexyl derivative 282 (Figure 15) was prepared by insertion of N-cyclohexyl isocyanideinto the Si�Si bond of a disilane in the presence of Pd(0) or Pt(0) as a catalyst. ThePd(0)-catalyzed method was further used to synthesize a wide range of N-aryl analogs.
The second method is based on a transmetallation reaction and can be applied to the synthesisof (2,6-xylimino)bissilanes 283 (Figure 15). This compound is obtained from (2,6-xylimino)(TMS)methyllithium by treatment with requisite chlorosilane.
In 1994 the regioselective functionalization of bis-(trimethylsilyl)methylimines with electrophileswas described <1994SL955>. Thus, silylated azomethines 284 are readily deprotonated in THF at�78 �C to give the 2-azaallyllithium compounds 285, which react further with electrophilicreagents to give functionalized silylated imino derivatives 286 (Scheme 70).
NR
SiR1R2R3R1R2R3Si
N
SiR1R2R3TMS
Me
Me N2
R1
R2
282 283
R = cyclohexyl, aryl SiR1R2R3 = TMS, TBDMS
287
Figure 15
NH
R
SiMe3
SiMe3
NH
R
SiMe3
SiMe3Li
NR1
R
SiMe3
SiMe3
H
284
Base
THF, –78 °C to rt
R1Cl
286285
Base = MeLi or LIDAKOR (the superbasic mixture of LIDA /ButOK)
R = Ph, alkenyl; R2 = Me3Si, COOEt
+
Scheme 70
Functions Containing an Iminocarbonyl Group 653
6.21.2.3.5 N-Haloiminocarbonyl derivatives
Electronic structures of the imines HalN=C(TMS)2 have been calculated, but no synthesis ofthis class is reported in the literature <1995COFGT(6)639>.
6.21.2.3.6 N-Aminoiminocarbonyl (diazomethane) derivatives
The following methods were described in chapter 6.21.3.1.4 in <1995COFGT(6)639>.Silylated and germylated lithiodiazomethanes undergo transmetallation reaction upon treat-
ment with chlorosilanes and chlorogermanes to give bis(silyl)diazomethanes (287, R1=TMS,(TMS)SiMe2, (TMS)3Si), and bis(germanyl)diazomethanes (287, R1=R2=GeMe3), respec-tively (Figure 15). Another method for preparation of these compounds involves thetransfer of the diazo group from tosyl azide to the carbanion derived from bis(TMS)- orbis(germyl)methanes.
In 1995 the bis(silyldiazomethyl)polysilanes 288 were prepared by lithiation of silyldiazo-methane followed by coupling with the corresponding dichloropolysilanes (Figure 16)<1995JOM(499)99>.
Diazogermylenes 289 were obtained in good yields by one-pot synthesis as described inScheme 71 <2001AG(E)952>. These compounds were found to be promising precursors toGe�C triple bonds (germynes).
6.21.2.3.7 N-Silyliminocarbonyl derivatives
N-silylated bis-(TMS)imines 290 (Figure 17) are formed as side products in the reaction ofsilaethene with silyl azides (RN3).
Since the publication of chapter 6.21.3.1.5 <1995COFGT(6)639> no advances have occurredin this area.
RMe2Si C Si C SiMe2RMe
MeN2 N2
Si SiMeMe
MeMe
Si Si SiMeMe
MeMe
Me
Me
Si Si SiMePh
MePh
Me
Me
Si Si SiMeMe
MeMeSi
Me
Me
Me
Me
n
288
A, n = 2, R = Me C, n = 3, R = Me
B, n = 3, R = Ph D, n = 4, R = Ph
Figure 16
ArBr
THF
ArLiGeCl2
THF
ArGeClN2
C SiMe3ArGenBuLi
THF/C6H14
289
Ar = 2,6 (R12NCH2)2C6H3
R1 = Et, Pri
Me3SiC(N2)Li
Scheme 71
654 Functions Containing an Iminocarbonyl Group
6.21.2.4 Iminocarbonyl Derivatives with One Metalloid Function and One Metal Function
6.21.2.4.1 N-Alkyl- and N-aryliminocarbonyl derivatives
These compounds bear resemblance to the iminocarbonyl derivatives with two metalloid func-tions, and are prepared in a similar manner either by insertion of alkyl and aryl isocyanides intometal–metal bonds or by transmetallation reactions <1995COFGT(6)639>. Thus, the Pd(0)-catalyzed insertion of isonitriles into Si�Sn bond of organosilylstannanes leads to the formationof organosilyl(N-alkylimino)stannanes (291, R1,R2=Me, R3=Pri, C6H11, C6H13, 2-MeC6H4;R1=Me, R2=But, R3=Pri; R1=Me, R2=But, R3=Pri). (2,6-Xylimino) (TMS)methyl-lithium has been converted into copper reagents 292 by transmetallation reaction with CuBr�SMe2or Cu acetylide (Figure 17) <1995COFGT(6)639>.
Recently, Xue and co-workers have studied in detail the insertion reactions of aryl isocyanidesinto the zirconium alkyl silyl complexes (293, R1,R2,R3=bn) <1998OM4853> and amido silylcomplexes (293, R1,R2,R3=Me2N, R1,R2=Me2N, R3= (Me3Si)2N) <1999OM1002>. In caseof alkyl silyl complexes the isocyanide insertion occurred exclusively into the Zr�Si bond to givethe product 296 as a result of silyl ligand migration (Scheme 72). Alternatively, the amido silylcomplexes containing different ligands offered the opportunity to observe the competitionbetween silyl and amido ligands in the migration step and to study whether silyl or amido ligandmigration is preferred. It was found that arrangement of ligands in 293 directs the attack of theisocyanide molecule. Thus, in amido silyl complex (Me2N)3ZrSi(SiMe3)3 the trans attack to thesilyl ligand results in the formation of 242. However, in case of (Me2N)2[(Me3Si)N]ZrSi(SiMe3)3,steric hindrance causes the isocyanide attack to take place cis to the silyl ligand with formation of294 where only amide migration is feasible giving rise to the formation of 296.
6.21.2.4.2 N-Aminoiminocarbonyl (diazomethane) derivatives
As described in chapter 6.21.3.2.2 in <1995COFGT(6)639>, these compounds are obtained bymetallation reactions. Reaction of silyldiazomethanes with BuLi gives lithium silyldiazomethanides(297, SiR3=TMS, tips, TMS-SiMe2). Treatment of (TMS)diazomethane with metal amides fur-nishes the plumbyl- and stannyl(TMS)diazomethanes 298. The stannyl(triisopropylsilyl)diazo-methane 299 can be obtained from the reaction of bis(trimethylstannyl)diazomethane with Pri3SiCl.
From the reaction of lithium silyldiazomethanide with Cl2Ni(PMe3)2 and Rh(PMe3)4Cl the(diazomethyl)trimethylsilanenickel(II) complex 300 and (diazomethyl)trimethylsilanerhodium(I)complex 301 were obtained, respectively (Figure 18).
Since the publication of chapter 6.21.3.2.2 in <1995COFGT(6)639> no advances haveoccurred in this area.
6.21.3 IMINOCARBONYL DERIVATIVES CONTAINING TWO METAL FUNCTIONS
The only compounds of this class mentioned in chapter 6.21.4 in <1995COFGT(6)639> were theorganometallic complexes with bridging isocyanide ligands.
RNTMS
TMSR3N
SnR31
SiMe2R2N
Me
MeSiR3
Cu
290
R = TMS, (TMS)2NSiMe2
291 292
Figure 17
Functions Containing an Iminocarbonyl Group 655
Iminocarbonyl derivatives 302 in which a C¼N double bond is bound to two Al atoms with veryshort Al�N bond are formed by the insertion of isonitriles into the Al�Al bond (Equation (30))<1994CB1587>.
Al AlCH(SiMe3)2
CH(SiMe3)2(Me3Si)2HC
(Me3Si)2HCAl
CH(SiMe3)2
N(Me3Si)2HC
(Me3Si)2HC
R
i
i. RCN, n-pentane, –25 °C to rt, 1 h
R = CMe3, Ph
302ð30Þ
Si(SMe3)3
ZrR3R1
R2
Si(SiMe3)3
ZrR3R1
R2
ArNC C
ZrR3R1
R2
NAr Si(SiMe3)3
Si(SiMe3)3
ZrR3R1
R2
Ar
C
ZrSi(SiMe3)3R1
R2
NAr R3
294
ArNC
293
Isocyanide attack cis to the silyl ligand
296
R1, R2, R3 = bn
R1, R2 = Me2N, R3 = (Me3Si)2N
295 242
Isocyanide attack trans to the silyl ligand
R1, R2, R3 = Me2N
CN
Scheme 72
N2
SiR3
LiN2
SiR3
MMe3
N2
SnMe3
SiPri3
N2
TMS
NiMe3P Cl
PMe3N2
TMS
RhMe3P
PMe3
PMe3
PMe3
297
M = Sn, Pb
298 299
300 301
Figure 18
656 Functions Containing an Iminocarbonyl Group
Other interesting examples of the complexes 303 which contain two different metals bound tothe iminocarbonyl group are obtained by insertion of MeNC into the polar M1�M2 bonds, asshown in Equation (31) <1996CC219>.
NSi
Si
Si N
M
Me2 Tol
M1(CO)2
TolMe2
Me SiMe2
N
Tol
Cp MeNCNSi
Si
Si N
M
Me2 Tol
TolMe2
Me SiMe2
N
Tol
N
M1(CO)2
Me
Cp
M
Ti
Ti
Zr
Hf
Zr
Hf
Fe
Ru
Fe
Ru
Fe
Ru303
M 1
ð31Þ
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658 Functions Containing an Iminocarbonyl Group
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Functions Containing an Iminocarbonyl Group 659
Biographical sketch
Franciszek Saczewski was born in Sopot, Poland on November 18, 1951.He graduated from Medical University of Gdansk in 1974 with M.S.degree in pharmacy and that same year began his career at the Depart-ment of Organic Chemistry. In 1981 he received his Ph.D. and in 1988D.Sc. degree in pharmaceutical chemistry, and in 1999 was promoted tofull professor. During 1983–1984 and 1988–1989 he was working withProf. Alan Roy Katritzky at the Department of Chemistry, University ofFlorida, USA. He is a member of the Royal Society of Chemistry (UK),International Society of Heterocyclic Chemistry, Polish PharmaceuticalSociety, and Polish Chemical Society.
Prof. F. Saczewski is currently the head of the Department of Chem-ical Technology of Drugs, Medical University of Gdansk, Poland. Hisresearch interests include the design and synthesis of nitrogen-containingheterocyclic compounds with potential circulatory, anticancer, and anti-HIV activities.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 605–660
660 Functions Containing an Iminocarbonyl Group
6.22
Functions Containing Doubly
Bonded P, As, Sb, Bi, Si, Ge, B,
or a Metal
V. D. ROMANENKO and V. L. RUDZEVICH
National Academy of Sciences of Ukraine, Kiev, Ukraine
6.22.1 FUNCTIONS CONTAINING DOUBLY BONDED P, As, Sb, or Bi 6626.22.1.1 General Remarks 6626.22.1.2 Dicoordinate Phosphorus and Arsenic Derivatives 6626.22.1.2.1 Dihalomethylenephosphines, Hal2C¼PY 6626.22.1.2.2 Oxygen- and sulfur-substituted methylenephosphines, RO(X)C¼PY
and RS(X)C¼PY 6646.22.1.2.3 Nitrogen-, phosphorus-, and arsenic-substituted methylenephosphines,
R2E(X)C¼PY (E=N, P, As) 6656.22.1.2.4 Silicon- and germanium-substituted methylenephosphines, R3Si(X)C¼PY
and R3Ge(X)C¼PY 6686.22.1.2.5 Metallated methylenephosphines, LnM(X)C¼PY 6716.22.1.2.6 C,C-diheterosubstituted methylenearsines, X2C¼AsY 673
6.22.1.3 Tricoordinate Phosphorus Derivatives 6756.22.1.3.1 Stabilized [X2C¼PY2]
+ species 6756.22.1.3.2 Functions with a phosphorus–metal �-donor bond, X2C¼P(MLn)Y 6766.22.1.3.3 �3�5-Methylenephosphoranes, X2C¼P(¼Z)Y 677
6.22.1.4 Tetracoordinate Phosphorus Derivatives 6806.22.1.4.1 Dihalosubstituted ylides, Hal2C¼PY3 6806.22.1.4.2 Oxygen-, sulfur-, and selenium-substituted ylides, RE(X)C¼PY3 (E=O, S, or Se) 6816.22.1.4.3 Nitrogen-, phosphorus-, arsenic-, and antimony-substituted ylides, R2E(X)C¼PY3
(E=N, P, As, or Sb) 6816.22.1.4.4 Silicon-, germanium-, and boron-substituted ylides, R3E(X)C¼PY3 (E=Si or Ge)
and R2B(X)C¼PY3 6856.22.1.4.5 Metal-substituted ylides, LnM(X)C¼PY3 686
6.22.1.5 Tetracoordinate Arsenic, Antimony, and Bismuth Derivatives 6876.22.1.5.1 C,C-Diheterosubstituted arsonium ylides, X2C¼AsY3 6876.22.1.5.2 Stibonium and bismuthonium ylides bearing heterosubstituents, X2C¼EY3 (E=Sb or Bi) 687
6.22.2 FUNCTIONS CONTAINING A DOUBLY BONDED METALLOID 6886.22.2.1 Tricoordinate Silicon and Germanium Derivatives 6886.22.2.1.1 Diheterosubstituted silaethenes, X2C¼SiY2 6886.22.2.1.2 C,C-Diheterosubstituted germaethenes, X2C¼GeY2 691
6.22.2.2 Functions Incorporating a Doubly Bonded Boron 6936.22.2.2.1 Methyleneboranes, X2C¼B-Y 6946.22.2.2.2 2-Borataallenes, [X2C¼B¼CY2]
� 6956.22.3 FUNCTIONS INCORPORATING A DOUBLY BONDED METAL 6956.22.3.1 Transition Metal–Carbene Complexes 6966.22.3.1.1 N-Heterocyclic carbene complexes 6966.22.3.1.2 Silicon-substituted carbene complexes, R3Si(X)C¼MLn 702
6.22.3.2 Functions with a Formal Tin–Carbon and Lead–Carbon Double Bond 704
661
6.22.1 FUNCTIONS CONTAINING DOUBLY BONDED P, As, Sb, or Bi
6.22.1.1 General Remarks
This section will survey the chemistry of functions X1X2C¼E (X1, X2=heteroatom substituents;E=P, As, Sb, or Bi) featuring a double bond between carbon and the heavier group 15 element.The known structural types of molecules containing these functions, arranged with increasingcoordination number of element, are listed below.
It is the peculiar �-bonding situation inducing a trigonal planar coordination around carbonwhich justifies the description of compounds A–C as heteroatom analogs of alkenes (Figure 1). Incontrast, the compounds of the type D contain the highly polarized C��E+ bond and can beconsidered either as ylides or as element-stabilized carbene species.
6.22.1.2 Dicoordinate Phosphorus and Arsenic Derivatives
This section concerns compounds of the type X1X2C¼EY (E=P, As) with three heteroatom–carbon bonds, whatever the nature of substituent on the phosphorus or arsenic. Since thepublication of chapter 6.22 in COFGT (1995) <1995COFGT(6)677>, the synthetic chemistryof phosphaalkenes and arsaalkenes has advanced dramatically. While no single review dealingspecifically with C,C-diheteroatom-substituted derivatives has been published, related surveyshave appeared. The most important of these are by Dillon and co-workers <B-1998MI>,Weber and co-workers <2002PS(177)1571, 2000EJI2425, 1999MI269, 1997MI1, 1996CB367,1996AG(E)271>, Mackewitz and Regitz <1998S125>, Yoshifuji <1997BCJ2881>, and Denisand Gaumont <1994CR1413>. There have been no experimental reports as yet of C,C-dihetero-substituted stiba- and bismaalkenes of the type X1X2C¼EY (E=Sb, Bi).
6.22.1.2.1 Dihalomethylenephosphines, Hal2C¼PY
A variety of routes developed for the synthesis of these compounds is presented in Scheme 1. By far themost general synthetic strategy involves the base-induced dehydrohalogenation of dihalomethylchlor-ophosphines (route ‘‘a’’). This method, as well as the dehalogenation of trihalomethylchlorophosphines(route ‘‘b’’), has become standard procedure for C,C-dihalophosphaalkene production. In addition,the dehydrohalogenation of trihalomethylphosphines (route ‘‘c’’) and the thermolysis of trifluoro-methyl(stannyl)phosphines (route ‘‘d’’) also provide dihalomethylenephosphines. It has to be pointedout that in contrast to the usual procedures in olefinic chemistry, only dehydrohalogenation ordehalogenation of sterically crowded phosphine precursors allows the isolation of monomericphosphaalkenes. Although electronic factors are not totally negligible, steric factors are of primaryimportance for the kinetic stabilization of dihalomethylenephosphines <1997MI343,1994ZOB1372>.
Ab initio molecular orbital calculations have been applied to determine the fluorine effect onthe stability of phosphaalkene F2C¼PF and its energetically low-lying rearranged isomers FC–PF2 (‘‘phosphinocarbene’’) and F3C–P (‘‘alkylphosphinidene’’). The phosphaalkene was shown tobe the most stable isomer; its energy differs from that of the phosphinocarbene by 161 kJ mol�1
<1997JOM(529)3, 1996MI85>. The kinetically stabilized C,C-difluorophosphaalkenes are nor-mally prepared by gas-phase thermal Me3SnF elimination starting from F3C(R)PSnMe3<1995COFGT(6)677, 1994CR1413>. Like alkenes, fluorine containing phosphaalkenes have amarked potential for undergoing cycloaddition reactions and, in view of the variety of 1,2- and1,3-dipoles available, they widen the scope of the phospha-heterocycle synthesis enormously<2001ZAAC(627)1241, 1997JOM(529)177, 1995JOC7439>.
A B C D
EX2
X1
YE
X2
X1
Y
YE
X2
X1
Y
Z
EX2
X1
YY
Y
+
Figure 1 Heteroatom analogs of alkenes.
662 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
Experimental details for the preparation of phosphaalkene 3 are described in Synthetic Methodsof Organometallic and Inorganic Chemistry <B-1996MI30>. Refluxing a solution of CHCl3, PCl3,and AlCl3 followed by treatment with MeOPCl2 gave dichloromethyl derivative 1 which ontreatment with Mes*Li (Mes*=2,4,6-tri-t-butylphenyl) gave the compound 2. The final conver-sion of 2 into phosphaalkene 3 has been accomplished through dehydrochlorination with DBU(Scheme 2).
Dillon and Goodwin have been able to prepare the phosphaalkene Cl2C¼PArf (Arf=2,4,6-tri-trifluoromethylphenyl) using a similar approach. The precursor phosphine Cl(Cl2CH)PArf wasprepared by two procedures, either directly by the action of ArfPCl2 on CHLiCl2, or via thecorresponding organocadmium reagent <1994JOM(469)125>.
The dehalogenation route has also received further attention. A range of new phosphaalkenesincluding the compounds 4–6 bearing very bulky groups has been prepared in recent years byEscudie and co-workers <1999PS(152)153>. A variant of dehalogenation reactions should bementioned which permits sterically crowded bis(trichloromethyl)phosphines (Cl3C)2PR (R=Mesor 2,2,6,6-tetramethylpiperidino) to be converted into phosphaalkenes 7 and 8 using (Et2N)3P<1994ZOB913>. In addition, further study has appeared of generation of the thermally unstablephosphaalkene Cl2C¼PCl <1995JOC7439>. Also reported in this study is a synthesis of thephosphaalkene precursor Cl2CHPCl2 from Cl2CHZnCl and PCl3.
YLi
–LiCl
YPHal2
YP(Li)H
Me3SnLi
–LiCl
Hal4C/R3P–R3PHal2
R3P or BuLi
–R3PHal2 or–BuHal, –LiHal
Hal4C–LiHal
a
b
c
d–Me3SnF
Y = preferably Alk, Ar, or R2N (routes "a", "b"), Ar (route "c"), F3C (route "d")
R = preferably But or Et2N; B = DBU or Et3N
–B.HHal
B
B
–B.HClPCl2
Hal
HalP
Y
Cl
Hal
Hal
Hal3C PY
Hal
PHal
Hal
Y
F3C PY
ClF3C P
Y
SnMe3
Hal3C PY
H
Scheme 1
CHCl3 PCl3
–DBU.HCl
–LiCl+
i. AlCl3ii. MeOPCl2 Mes*Li
DBU/
Mes* = 2,4,6-tris(t-butyl)phenyl
1 (42%)
2 3 (72%)
PCl
Cl
Cl
Cl
PMes*
Cl
Cl
ClP
Mes*Cl
ClTHF
Scheme 2
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 663
4, Ar = Mes
5, Ar = p-MeOC6H4
6, Ar = p-MeC6H4
7 8
PCl
ClP
Cl
ClAr
Ar
PCl
Cl
N
The importance of steric protection for the stability of C,C-diiodophosphaalkenes, I2C¼PR,was investigated by varying the size of group R. The phosphaalkene I2C¼P-Is (Is=2,4,6-Pri3C6H2) could be prepared in 15% isolated yield by reaction of IsPCl2 and CHI3 with2 equiv. of LDA, in analogy to the synthesis of the stable, sterically more protected I2C¼P-Mes* (Mes*=2,4,6-But3C6H2). If the steric protection on the phosphorus was decreased further(R=Es=2,4,6-Et3C6H2, R=Mes=2,4,6-Me3C6H2), the substituted phosphines RP(Cl)NPri2(R=Es, Mes) were formed as main products, in addition to thermally unstable phosphaalkenesI2C¼P-Es and I2C¼P-Mes. The reaction of I2C¼P-Mes* with bromine gave an (E)/(Z) mixtureof the C-bromo-C-iodophosphaalkene Br(I)C¼P-Mes*. Further reaction with bromine pro-ceeded via Br2C¼P-Mes* and finally led to Br(Br2CH)P-Mes* <1994RTC278>.
6.22.1.2.2 Oxygen- and sulfur-substituted methylenephosphines, RO(X)C¼PYand RS(X)C¼PY
Among the most common routes for the synthesis of these compounds are those based onelimination and silyl migration reactions (Equations (1) and (2)) <1995COFGT(6)677>.
–HCl
1,2-Elimination
X = O, S
PRX
RX
Y
ClP
RX
RX
Y ð1Þ
–HCl
X = O, S
PRX
X
Y
TMSP
RX
X
Y
1,3-Me3Si shift TMS
ð2Þ
In an interesting extension of the 1,2-elimination methodology, it has been found that lithiumbis(trimethylsilyl)phosphide reacts with an excess of dimethyl carbonate to afford the bis(1,2-dimethoxyethane-O,O0)lithiooxymethylidynephosphine 10. The phosphaalkene 9 is probably anintermediate in this reaction but it has not been detected directly (Scheme 3)<1992ZAAC(612)72>.
(TMS)2PLi +DME, –20 °C
9
–MeO–TMS
–MeO–TMS
OMeO
MeO
PMeO
LiO
TMSC P.2DMELiO
(TMS)2P
OMe
OMe
LiO
79%
Scheme 3
664 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
The silatropic principle combined with the insertion reaction has been used to prepare therather unstable metallophosphaalkenes 11, which decomposed to the doubly metallated 1,3,4-thiadiphospholes by extrusion of (TMS)2S. However, the compounds 11 were intercepted asisolable [(CO)5Cr]-adducts 12 by treatment with [(Z)-cyclooctene]Cr(CO)5 (Scheme 4)<1997OM3188>.
Yoshifuji and co-workers utilized an in situ generation-capture methodology for the synthesisof phosphaalkenes (Z)-14 and 15 via reaction of the C,C-dibromophosphaalkene 13 with butyl-lithium and diphenyldisulfide (Scheme 5) <1998CL651>. This development was the key tofurther applications of the sulfur-substituted phosphaalkenes <2000CL1390>.
6.22.1.2.3 Nitrogen-, phosphorus-, and arsenic-substituted methylenephosphines,R2E(X)C¼PY (E=N, P, As)
(i) From C,C-dihalomethylenephosphines
A kinetically stabilized phosphanylidene carbenoid (Z)-16 was prepared from the phosphaalkene3 and butyllithium (vide infra), and was allowed to react with Ph2PCl to afford the corresponding2-chloro-1,3-diphosphapropene (Z)-17 in good yield (78%) after silica-gel column chromato-graphic purification. Similarly, starting from (E)-16 and Ph2PCl, an attempt was made tosynthesize (E)-17. Although NMR signals due to (E)-17 were observed in the reaction mixture,the latter was isomerized to (Z)-17 after the usual work-up procedure. The treatment of (Z-)17with [W(CO)5(THF)] leads to the complex (Z)-18 with the metal carbonyl group at the lesshindered phosphorus atom (Scheme 6) <2001CC1208>.
Of the compounds of the type Hal(R2As)C¼PY, up to now 19 has been isolated from thereaction of 1-bromo-2-phosphaethenyllithium with Mes*AsF2 (Scheme 7). Further addition of n-butyllithium to 19 at �90 �C led to the organolithium intermediate, which lost LiF to give innearly quantitative yield the arsaphosphaallene Mes*-As¼C¼P-Mes* <1998OM1631>.
(ii) Synthesis by condensation reactions
The starting point for the now extensive chemistry of the C,C-bis(dialkylamino)methy-lenephosphines was the synthesis of (R2N)2C¼P-TMS via the condensation of (TMS)3Pwith (R2N)2CF2 <1995COFGT(6)677>. The generality of this approach is restricted, however,by possible difficulty in the preparation of the requisite geminal difluorides <2002CC1618>.An alternative route to the phosphaalkene 20a is provided by the reaction of S-methyl
[M]-P(TMS)2CS2
11
[M] = Cp*(CO)2M; M = Fe, Ru
L = (Z )-cyclooctene
Pentane, rt
12
LCr(CO)5
Benzene, rtP
[M]
Cr(CO)5
S
STMS
TMSP
[M]S
STMS
TMS
M = Fe (40%)
M = Ru (32%)
Scheme 4
i, ii i, ii
Z-14 15
55% 51%
i. BunLi, THF, –100 °C; ii. PhSSPh, THF, –78 °C to 0 °C
13
PMes*
PhS
PhSP
Mes*
PhS
BrP
Mes*
Br
Br
Scheme 5
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 665
bis(dimethylamino)thiouronium iodide with lithium bis(trimethylsilyl)phosphide (Equation (3)).Spontaneous condensation occurred upon mixing of equimolar amounts of the reagents in amixture of pentane and 1,2-dimethoxyethane <1995S158, 2000EJI1185>.
I– (TMS)2PLi.DME
–LiI, –MeS–TMS, –DME73%
SMeMe2N
Me2NP
Me2N
Me2N
TMS
-X+
20a
ð3Þ
(iii) Synthesis via free carbenes
It has been demonstrated that N-heterocyclic carbenes are sufficiently nucleophilic to depolymer-ize cyclopolyphosphines such as (PPh)5 and (PCF3)4 and produce compounds of the type 21,which can be formulated either as phosphaalkenes or as carbene–phosphinidene complexes(Equation (4)) <1997CL143, 1997IC2151>. The latter formulation is favored by the observationthat treatment of the compounds 21 with boranes results in the formation of P,P-bis(borane)complexes, indicating the availability of two lone pairs at phosphorus <1997CC981>.
+ 1/x (R3P)x THF, rt
21a–21c
N
NR2
R2
R1
R1N
NR2
R2
R1
R1
PR3 N
NR2
R2
R1
R1
PR3
+ –
Me
Mes
Mes
R 1 21
a
b
c
R 3
Ph
Ph
CF3
R 2
Me
H
H
ð4Þ
Ph2PCl W(CO)5(THF)
Ph2PCl
78% 39%
(Z )-16
(E )-16 (E )-17
(Z )-17 (Z )-18
PCl
Ph2P
Mes*P
Cl
Li
Mes*P
Cl
Ph2P
Mes*
W(CO)5
PPh2P
Cl
Mes*P
Li
Cl
Mes*
Scheme 6
13 19
BunLi Mes*AsF2
Et2O, –100 °CP
Mes*
Br
BrP
Mes*
Li
BrP
Mes*
As
Br
FMes*
27%
Scheme 7
666 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
It is also possible to prepare bis(amino)phosphaalkenes by direct reaction of a nucleophiliccarbene with dichlorophenylphosphine. This approach is illustrated in Equation (5) for thesaturated 1,3-dimesitylimidazolin-2-ylidene <1997IC2151>. The generality of this methodologyis restricted, however, by difficulties in the preparation of the starting carbene.
Cl–+
+THF, rt, 1 h
69%
2 + PhPCl2N
NMes
MesN
NMes
Mes
PPh N
NMes
Mes
Cl ð5Þ
(iv) Derivatization of P-hydrogen- and P-silyl-methylenephosphines
P-Hydrogen- and P-silyl-substituted phosphaalkenes of the type R2N(Y)C¼PX (X=H, TMS)are important reagents for the introduction of R2N(Y)C¼P groups into organic molecules viaelectrophilic substitution at the dicoordinated phosphorus atom. In particular, treatment of theeasily accessible phosphaalkene Et2N(F)C¼PH ((E)/(Z)=18/82) with halophosphines andhaloarsines in the presence of triethylamine as base provides a route to the P-phosphino and P-arsino derivatives Et2N(F)C¼P-ER2 (E=P, As) <1996ZN(B)778>. 1-Diethylamino-1-fluoro-2-phosphaalkenes of the type Et2N(F)C¼P-ER3 [R3E=TMS, Me3Ge, (F3C)3Ge and Me3Sn) areprepared in moderate yields by reaction of Et2N(F)C¼PH with R3EX (X=Cl, I). The relativelystable derivative Et2N(F)C¼P-TMS was used as a substrate for reactions with pivaloyl,adamantoyl, and benzoyl chloride, respectively, which by cleavage of the Si–P bond yield the‘push/pull’ phosphaalkenes Et2N(F)C¼P-C(O)R (R=But, Ad, Ph) <2000ZAAC(626)1141>.Similarly the phosphaalkene 20a was transformed into the P-acyl derivatives (Me2N)2C¼P-C(O)R (R=But, Ph) when allowed to react with an equimolar amount of pivaloyl or benzoylchloride <1998OM3593>.
The phosphaalkenyl functionalized carbyne complexes 23 have been obtained by reacting thechlorocarbyne complexes 22 and P-silylated phosphaalkenes 20 (Equation (6)) <1997CB1305>.The reaction of 20 with Cp*(CO)2MBr (M=Fe, Ru) in hydrocarbon solvents at room tempera-ture affords moderate yields of the metallophosphaalkenes 24 (Equation (7)) <2000EJI1185,1993ZN(B)1784>.
Cl C M(CO)2Tp'–TMS–Cl
20a, b23
Tp' = HB(3,5-Me2C3HN2)3; M = Mo, W; R = Me (a), Et (b)
22
PTMS
R2N
R2NP
C
R2N
R2NM(CO)2Tp'
+
ð6Þ
+32–69%
M = Fe, Ru; R = Me (a), Et (b)
20a, b 24
MOC Br
CO
PTMS
R2N
R2NP
M
R2N
R2NCOOC ð7Þ
(v) Miscellaneous
C-Phosphino-phosphaalkenes 25 are formed in the thermal ring opening of diphosphiranes, atheoretical study suggesting the intermediacy of diradical species <1994IC596>. In the presenceof either boron trifluoride or triflic acid, the diphosphapropene 26 gives the diphosphaallyliccation 27, which is then transformed into the four-membered ring system 28. In the presence of abase, the latter converts to the three-membered system 29 <1994JA6149>.
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 667
++
25 26 27 28 29
PCl
R2PMes* P
NR2
(R2N)2P
R2NP
NR2
P
R2N
R2NP
NP
NR2
NR2
R R
P P
NR2
NR2
NR2
+
On heating in toluene the 1,3-diphosphacyclobutane-2,4-diyl 30 isomerizes by cleavage of theP�C bond to give the diphosphapropene 32. A plausible intermediate of this reaction is thephosphinocarbene 31, which results from a ring opening and stabilizes by CH activation of anortho-positioned t-butyl group to give 32 (Scheme 8) <1995AG(E)555>.
6.22.1.2.4 Silicon- and germanium-substituted methylenephosphines, R3Si(X)C¼PYand R3Ge(X)C¼PY
The heavier group 14 elements, especially silicon, exert a stabilizing effect on the methylenepho-sphine function and consequently numerous C-silyl-substituted phosphaalkenes have been synthe-sized and thoroughly studied. The development of C-germylated phosphaalkenes has proceededat a slower pace and has not yet reached the degree of complexity of its silicon counterparts.However, in the 1990s a range of C-germyl-substituted phosphaalkenes has become available, andrecent works have demonstrated that many of these compounds exhibit excellent thermal stability.
(i) From C,C-dihalomethylenephosphines
A halogen–metal exchange/coupling route is the most effective for the preparation of highly functio-nalized phosphaalkenes R3E(Hal)C¼PY (E=Si, Ge) as it permits a chemical variation of thesubstituent pattern with retention of the P¼C unit. Several examples of the use of this strategyhave been reported. For example, addition of n-butyllithium to the phosphaalkene 13 at low tem-perature with subsequent quenching the resulting lithio derivative with chlorotrimethylsilane furn-ished (Z)-33 in 98% isomeric purity <1996OM174>. Conversion of the phosphaalkene (Z)-33 to thecorresponding lithio derivative with n-butyllithium, followed by the addition of 1,2-dibromoethaneproduced the silylated species (E)-33 as the only isomer (Scheme 9) <1997JOM(529)107>. A similarapproach has been used for the preparation ofC-germyl substituted phosphaalkene 34. The best yieldin 34 was obtained when the reaction mixture was stirred for 1 h at �80 �C, after addition of thedifluorogermane to 13 at �100 �C. The phosphaalkene 34 can also be obtained in one pot by adding2 equiv. of BunLi to a mixture of 13 and Mes2GeF2 in Et2O since at �120 �C butyllithium does notreact with the Ge�F bond of difluorodimesitylsilane (Equation (8)) <1996OM3070>.
Toluene, 100 °C
30 31
32
P PMes* *Mes
Cl
Cl
P PMes* *Mes
Cl
ClP
P
Cl
Me
ClMe
H
Mes*X
X
Scheme 8
i. BunLi i. BunLi
ii. TMS-Cl
–130 °C
ii. BrCH2CH2Br
THF, –110 °C
13 (Z )-33 (90%) (E )-33 (60%)
PMes*
Br
BrP
Mes*
TMS
BrP
Mes*
Br
TMS
Scheme 9
668 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
i. BunLiii. Mes2GeF2
Et2O, –100 °C
13 34
PMes*
Br
BrP
Br
Mes2GeMes*
F
35%
ð8Þ
The carbenoid Cl(Li)C¼PMes*, which is much more stable than its bromo analog, has alsobeen shown to behave as a nucleophile when treated with halogermanes. Thus, reaction of2-phosphaethenyllithium with difluoro(mesityl)(fluorenyl)germane afforded the fluoro(germyl)pho-sphaalkene 35 in 77% yield. In contrast, the chloro analog 36 was obtained only in very lowyield (�10%). However, the phosphaalkene 36 could be prepared in good yield by a two-stepprocedure involving the prior reaction of the carbenoid Li(Cl)C¼P-Mes* withtrichloromesitylgermane, followed by the addition of fluorenyllithium <1999OM1622>. Asa further development of this work the synthesis of germylphosphaalkene 38 has beenachieved starting from dichlorophosphaalkene 3 and difluorogermane 37 (Scheme 10)<2002JOM(643/644)202>.
(ii) By elimination reactions
An example from recent literature includes an improved procedure for the preparation of P-chloro-bis(TMS)methylenephosphine 39 (Scheme 11) <B-1996MI34>.
i. BunLiii. Mes(R2CH)GeX2
i. BunLiii. MesGeCl3
35, X = F
36, X = Cl
3
R2CHLiTip(But)GeF2
37
38
R2CH = ; Tip = 2,4,6-Pr3C6H2; Mes* = 2,4,6 = Bu3C6H2i t
THF, –78 °C
THF, –78 °C
PMes*
Cl
ClP
Mes*
Ge
Cl
X MesR2HC
PMes*
Cl2Ge
Cl
Mes
PMes*
Ge
Cl
Tip But
F
Scheme 10
Et3N
Et2O, rt
i. Mgii. PCl3
Et2O/THF
39
PCl
TMS
TMSPCl2
TMS
TMSCl
TMS
TMS
70%
Scheme 11
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 669
(iii) By derivatization of P-halo-C,C-bis(TMS)methylenephosphines
A very useful technique for the direct introduction of the (TMS)2C¼P moiety into a variety ofmolecules is based on the nucleophilic substitution at the dicoordinated phosphorus atom.Phosphaalkenes (TMS)2C¼P-Y (Y=Hal, TfO) are particularly useful for the creation of newphosphorus–carbon and phosphorus–heteroatom bonds. The nucleophiles more commonlyemployed are Grignard and organolithium reagents as well as R2N, RO, RS�, and R2P
� anions<1995COFGT(6)677>. However, progress has recently been made with functionalized nucleo-philic species.
Recent work has shown that 2,2-bis(TMS)-1-phosphaethenyl substituted pyridines 41 may beprepared by the reaction of lithium salt of the bifunctional carbanions 40 with phosphaalkene 39(Equation 9) <2002AG(E)3367>.
+N
RR
Li LiEt2O, –78 °C
rac/meso-41R = Ph, TMS
39
NR R
P P
TMS
TMS
TMS
TMSP
Cl
TMS
TMS
40
ð9Þ
Particular success was achieved using heteroatom nucleophiles as the substrates. Treatment of39 with 2 equiv. of (TMS)2PLi in DME gave lithium salt of 1,2-diphosphapropenide 42 in 76%yield. Subsequent reaction of 42 with additional (TMS)2PLi provides a route to the 2,3,4-tripho-sphapentadienide system 43, an intermediate for the synthesis of heterocyclic phosphorus com-pounds <1996AG(E)313>. Reactions of equimolar amounts of (�5-C5Me5)(CO)2Fe-E(TMS)2(E=P, As) with 39 afforded the 1-metallo-1-phospha(arsa)-2-phosphapropenes 44 <1995CB665,1996CB219>.
PP
TMS
Li+(DME)
PP
P
Li+(DME)
42 4344 (E = P, As)
TMS
TMS
TMS
TMS
TMS
TMSP
EFe(CO)2(Cp*-η5)
TMS
TMSTMS
Reaction of 39 with AlCl3 in the presence of Ph3P results in the formation of the phosphineadduct of a methylenediylphosphenium cation 46. A similar product 47 containing the samecation was obtained by treatment of the phosphaalkene 45 with Ph3P. Finally, the phosphaalkene46 reacts with (Ph3P)2Ni(COD) to give the complex 48 via a phosphine shift from phosphorus tothe metal (Scheme 12) <1994JA2191>.
AlCl4–AlCl3, Ph3P
Y = Cl
39, Y = Cl
45, Y = TfO
Ph3P
Y = TfOTfO–
(Ph3P)2Ni(COD)
–COD
46
47 48
PY
TMS
TMS
PPPh3
TMS
TMS+
PPPh3
TMS
TMS+
PTMS
TMS
+Ni(PPh3)3
AlCl4–
Scheme 12
670 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
Fischer-type carbene pentacarbonyltungsten complexes, which are functionalized by thebis(TMS)methylenephosphino moiety bonded to oxygen 49 or nitrogen 50, are synthesized byreaction of the O-Li and N-Li precursor carbene complexes with 39 (Equation (10))<2000JOM(613)56>. Concerning the last example, it is worth noting that metallaheterobutadienespecies of the type 50 easily rearrange into 2H-azaphosphirenes <2000EJI1253, 2001JOM(617/618)423, 2002JOM(643/644)253>.
+Et2O, –30 °C
49, X = O
50, X = NH
39
(OC)5WPh
XLiP
TMS
TMS
ClP
TMS
TMS
XW(CO)5
Ph
ð10Þ
(iv) Miscellaneous
Dichlorophosphino ylide TMS(Cl2P)C¼PPh3 loses a chloride ion to Lewis acidic metal chlorides(AlCl3, GaCl3, and SnCl4). In the (E)- and (Z)-isomers so generated, a considerable part of thephosphenium charge is transferred to the phosphonium center leading to a phosphaalkenestructure 51 <1996HAC355>.
So far, very little is known about compounds containing a Ge2C¼PY backbone. In view ofthis, it is interesting to note that in the absence of trapping reagent, the germaphosphaalleneMes2Ge¼C¼P-Mes* gives two types of dimers: the ‘‘classical’’ head to tail dimer 52 and thedimer 53 due to cycloaddition between a Ge¼C and a P¼C double bond. The dimer 53 is themajor product <1996OM3070>.
51
MCln = AlCl4, GaCl4, SnCl5 52
R = 2,4,6-Bu3C6H2t R = 2,4,6-Bu3C6H2
t
53
Ge
GePP RR
RR
RR
P
GePGe
R R
RR
RR
PPh3P
TMSCl+
MCln–
6.22.1.2.5 Metallated methylenephosphines, LnM(X)C¼PY
These have been intensively studied in the last few years because of their potential as syntheticblocks in organic chemistry <1995CB465, 1996OM174, 1998CL651>.
(i) Phosphaalkenyl metal species
The compounds M(Hal)C¼PY are the phosphorus analogs of alkylidene carbenoids and usefulsynthons for novel C-functionalized phosphaalkenes (vide supra).
Halogen–lithium exchange reactions provide the most general method for the preparation ofphosphaalkenyllithium derivatives. Recently new developments in this area have been reported.Treatment of THF or DME solutions of the phosphaalkene Cl2C¼PMes* 3 with excessn-butyllithium afforded cleanly the corresponding carbenoid as DME-solvate ((Z)-54a) or THF-solvate ((Z)-54b). (E)-54 was generated analogously by metallation of (E)-Cl(H)C¼P-Mes* withexcess BunLi and identified by 31P NMR spectroscopy. Unlike the (Z)-isomer, (E)-54 was foundto be unstable under reaction conditions and decomposed to give Mes*C¼P and Mes*(Li)C¼P-Bun as main products <1999JA519>.
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 671
(Z )-54a (solv = DME, n = 2)
(Z )-54b (solv = THF, n = x)
(E )-54 (solv = THF, n = x)
PMes*Cl
PMes*
Cl(solv)n Li
(solv)n Li
The phosphaethenyllithium reagent 54 was transmetallated with MgBr2, ZnCl2, and HgCl2 tofurnish the new carbenoids 55. Bis(phosphaalkenyl)–metal species 56 can be made by reacting(Z)-54 with 0.5 equiv. of the metal halide (Scheme 13). The stability order of the newly formedphosphavinylidene carbenoids corresponds to the expected sequence Li<Mg<Zn<Hg. Whereas(Z)-54 decomposes at temperatures above �50 �C, the magnesium carbenoids 55a and 56a slowlydecompose at 15 �C. The zinc carbenoids 55b and 56b are stable at room temperature for at leasta few days. The mercury carbenoids 55c and 56c are the most stable one; they can be stored atroom temperature in the air <1996OM174>.
Bromium–lithium exchange at �90 �C between (Z)-Br(TMS)C¼PMes* and BunLi furnished((E)/(Z))-Li(TMS)C¼PMes* ((E)/(Z)=1:1). Transmetallation of the latter with MgBr2 or ZnCl2furnished only the trans-metal isomer of XM(TMS)C¼PMes* (MX=MgBr, ZnCl)<1996OM174>.
A convenient synthesis of 1-arylthio-2-phosphaethenyllithiums (Z)-57 is based on bromine-lithium exchange of (Z)-14 with n-butyllithium. During the reaction, the (E)/(Z)-isomerizationwas observed even at �100 �C in THF. Treatment of (Z)-57 with 0.5 equiv. of HgCl2 in THFaffords the corresponding organomercury compounds 58. The transmetallation with CuCl2 givesthe 1,4-diphospha-1,3-butadiene derivatives 59 as homocoupled products presumably via thecorresponding phosphaalkenylcopper species (Scheme 14) <2000CL1390>.
(ii) Bridging aryl isocyaphide ligands
Weber and co-workers <1993ZAAC(619)1759> reported the synthesis of a diiron complex 60 witha bridging CPR ligand in which the aryl isocyaphide isC-bonded to twometal atoms (Equation (11)).
Fe Fe
S Me
O
COOC
CpCp
+
Mes*P(TMS)H, DBU
–TMS–SMe, –DBU.H+Fe Fe
P
O
COOC
CpCp
Mes*
60
ð11Þ
55a–55c
M = Mg (a), Zn (b), Hg (c)
MX = MgBr (a), ZnCl (b), HgCl (c)
(Z )-54
56a–56c
MX2
THF, –110 °C
THF, –110 °C
0.5 MX2 PM
ClMes*
ClP
Mes*
Li
ClP
Mes* ClP
Mes*
XM
Scheme 13
672 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
Further consideration has been given to the semi-bridging isocyaphide platinum complexes 63<1994OM2454, 1994OM2444>. The syntheses of 63 begin with the platinum complexes 61,whose preparation was reported previously <1993OM4265>. Although no intermediates wereobserved by 31P NMR spectroscopy during the reaction with Pt(PEt3)4, a possible mechanism forthe formation of 63 could involve intermediates 62 resulting from oxidative addition of the C-Halbond to Pt(PEt3)4. Loss of PEt3 from this intermediate followed by Pt�Pt bond formation wouldgive the final product. Complexes 63 were also prepared by the direct reaction of Cl2C¼PMes*with 2 equiv. of Pt(PEt3)4 in benzene at room temperature but the yield (<40%) was much lowerthan that obtained from the reaction of 61 with Pt(PEt3)4 (Scheme 15).
6.22.1.2.6 C,C-diheterosubstituted methylenearsines, X2C¼AsY
In comparison with C,C-diheterosubstituted phosphaalkenes, the area of corresponding moleculeswith an arsenic–carbon double bond is rather poorly explored. Even so, since 1994 variousmethods for the synthesis of hetero substituted arsaalkenes have been developed. Some of themmirror the methods elaborated for the synthesis of the related phosphaalkenes.
As shown in Scheme 16 the action of some lithiated halomethanes on Mes*AsF2 affordsarsaalkenes halogenated at the alkene carbon atom. Thus, the dibromoarsaalkene 64 was pre-pared by a one-pot synthesis from an aryldifluoroarsane and LiCHBr2. The C,C-dichloro- andC,C-diiodo-arsaalkenes 65 and 66 were prepared by a similar route from Mes*AsF2 and, respec-tively, LiCCl3 and LiCI3. However, in contrast to the synthesis of 64, in which 2 equiv. ofLiCHBr2 was required, only 1 equiv. of LiCCl3 and LiCI3 was used; the formation of 65 and 66from the probable intermediates X3C�As(F)Mes* was effected by addition with a secondequivalent of n-butyllithium at �90 �C <1996OM2683>.
BunLi
THF, –100 °C
0.5 HgCl2
CuCl2
60–79%
O2
38–84%
(Z )-14 (E )-57 (Z )-57
58
59Ar = Ph, 4-MeC6H4
–100 °CP
Mes*
ArS
BrP
Mes*
ArS
LiP
Mes*
Li
ArS
PMes*
Cu
ArS
HgS
P Mes*
Ar
S
PMes*
Ar
S P
S PMes*
Mes*
ArAr
Scheme 14
PtL4
Benzene, rt –L
63
Hal = Cl, Br; L = Et3P
6162
PMes*
Pt
Hal
Hal LL P
Mes*
Pt
Pt
Hal LL
Hal
L
L
PMes*
Pt
Pt
Hal LL
LHal
60–65%
Scheme 15
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 673
[1,3]-Silyl migration in combination with the preceding addition reaction, described for thesynthesis of phosphaalkenes, can also be used to obtain arsaalkenes. Thus, the reaction ofthe metalodisilylarsanes Cp*(CO)2M-As(TMS)2 (M=Fe, Ru) with carbon disulfide furnishedthe metaloarsaalkenes (TMS-S)2C¼P-M(CO)2Cp* as isolable compounds in yields up to 80%<1997OM3188>.
The reaction of (CF3)2AsH with secondary amines in a molar ratio of 1:3 allows the preparationof C-fluoro-C-aminoarsaalkenes 68a–68c in 15–35% yield. The main product of the reaction withdimethylamine is the bis(amino)methylenearsine 69a. With Et(Pri2)NH or Pri2NH the correspond-ing derivatives F[Pri(Et)N]C¼As-CF3 68d and F(Pri2N)C¼P-CF3 68e, respectively, are formedonly in traces 68d, or not at all 68e. The synthesis is assumed to involve an initial base-assisted HFelimination to the transient 2-arsaperfluoropropene 67. This step is seriously hindered for the bulkyamines and the formation of the corresponding arsaalkenes 68d,68e is suppressed. Evidence for thisidea is provided by the direct conversion of 67 into [Pri2(Et)N]2C¼As-CF3 69d and (Pri2N)2C¼P-CF3 69e by exposure to the respective amines (Scheme 17) <1995ZN(B)94>.
The C,C-bis(amino)arsaalkene 70 have been obtained from the reaction of LiAs(TMS)2�2THFwith a thiuronium iodide (Equation (12)). Spontaneous condensation occurs upon mixing ofreagents in pentane to give 70 as orange oil in 78% yield <1996CB367>. Condensation ofTp0(CO)2M�CCl (M=Mo, W; Tp0=HB(3,5-Me2HC3N2)3) with the arsaalkene 70 affordedthe novel arsaalkenyl carbyne complexes Tp0(CO)2M�C-As¼C(NMe2)2 (M=Mo, W)<1999OM4603>. Another type of periphery reaction takes place when the arsaalkene 70 istreated with (�5-Cp*)(CO)2FeBr n-pentane. Microcrystalline brown metaloarsaalkene (�5-Cp*)-(CO)2Fe-As¼C(NMe2)2 is isolated in 44% yield <1996CB223>.
+I–
70
LiAs(TMS)2.2THF
78%SMeMe2N
Me2NAs
TMS
Me2N
Me2Nð12Þ
LiCHBr2 LiCHBr2
THF, –100 °C
THF, –90 °C
LiCHal3
64
65, Hal = Cl
66, Hal = IMes* = 2,4,6-Bu3C6H2t
BunLi
Mes* AsF2 AsMes*
F
Br
BrAs
Mes*Br
Br
AsMes*Hal
HalAs
Mes*Hal
HalHal
F
46%
56–64%
Scheme 16
(CF3)2AsHR2NH 2 R2NH
+
68a–68c
69a–69e68, 69 a b c d e
R2N Me2N Me(Et)N Et2N Et(Pri)N Pr2i N
–60 °CAs
CF3
F
F
AsCF3
R2N
R2N
AsF
R2NCF3
67
Scheme 17
674 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
The reaction between nucleophilic carbenes and pnictinidene oligomers described in Section6.22.1.2.3 also occurs in the case of arsenic. 1,3-Dimesitylimidazol-2-ylidene reacts with hexa-phenylcyclohexaarsane to form the arsaalkene 71. The reaction appears to tolerate strongly�-electron-withdrawing substituent on arsenic. For instance, the arsaalkene 72 was obtained in61% yield by reacting 1,3-dimesitylimidazol-2-ylidene with tetrakis(pentafluorophenyl)cyclo-tetraarsane (Equation (13)) <1997IC2151>.
+ 1/x (RAs)xTHF, rt
71, R = Ph
72, R = C6F5R = Ph, x = 6; R = C6F5, x = 4
N
NMes
Mes
AsRN
NMes
Mes ð13Þ
With the arsaalkene 64 as starting material, the new C-bromo-C-silyl-substituted arsaalkene 73was obtained by successive reaction with n-butyllithium and chlorotrimethylsilane (Scheme 18).The air-stable 73 can be further functionalized by means of Li/Br exchange <2002OM1531>. In asimilar way, treating 64 with n-butyllithium in ether at �90 �C and then with Mes*AsF2 gave thearsaalkene 74 which is a valuable precursor for the synthesis of 1,3-diarsaallene Mes*-As¼C¼As-Mes* <2000JA12880>.
6.22.1.3 Tricoordinate Phosphorus Derivatives
6.22.1.3.1 Stabilized [X2C¼PY2]+ species
Several synthetic routes to the methylenephosphonium ions have been developed, but each one isappropriate for only a limited number of substrates <1997ACR486>. The most general synthesisis based on the heterolytic cleavage of a P�Cl bond in compounds of the type X2C¼P(Cl)Y2.Thus, the attack of AlCl3 on the P�Cl bond in the ylide 75 generates the methylenephosphoniumsalt 76 (Equation (14)) <1992AG(E)99>. The limitation of the method is illustrated by thereaction of ylide 77 with GaCl3 which affords the covalent complex 78 and not the correspondingmethylenephosphonium salt (Equation (15)) <1995OM3762>.
AlCl3
76
PTMS
TMSBut
Cl
But
75
AlCl4–P
TMS
TMS
But
But+
CH2Cl280%
ð14Þ
TMS-ClBunLi
THF, –90 °C –90 °C
7364
Mes*AsF2
74
As
Mes*
Br
BrAs
Mes*
Li
BrAs
Mes*
TMS
Br
As
Mes*
As
Br
Mes*F
Scheme 18
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 675
PCl
NR2
NR2
GaCl3
77 78
GaCl3
P(NR2)2
Cl+
– ð15Þ
At least in a very formal sense, one can consider the compounds 79 produced by reaction of themetallophosphaalkene 24a with trifluoromethanesulfonates as methylenephosphonium deriva-tives, although it is obvious that the real bonding pattern of these species is much closer to thephosphanyl-substituted carbenium salts (Equation (16)) <1999OM4216>.
F3CSO2OR
F3CSO3–
[Fe] = Cp*(CO)2Fe; R = Me, Me3SiCH2, Me3Si
7924a
P[Fe]
R
Me2N
Me2NP
[Fe]
R
Me2N
Me2NP
[Fe]Me2N
Me2N ++
ð16Þ
6.22.1.3.2 Functions with a phosphorus–metal s-donor bond, X2C¼P(MLn)Y
Basically, three strategies are used for the preparation of the title compounds: (i) complexation of ametal species with a phosphaalkene which already possesses the P¼C double bond<1988CRV1327,1997BSJ2881>; (ii) the ‘‘phospha-Wittig route’’ <1992ACR90>, and (iii) an approach based on thereactions of terminal phosphinidene complexes <1994CRV1413>. The C,C-dihetero-substitutedspecies are usually obtained via the complexation of free phosphaalkenes. Examples from recentliterature are presented in Equations (17)–(19) <1999EJI1607, 2002EJI3272, 2001CC1208>.
MMe3
n-Pentane, –78 °C 41–59%
E = P, As; [Fe] = Cp*(CO)2Fe; M = Al, Ga, In; <1999EJI1607>
E[Fe]
Me2N
Me2NE
[Fe]
Me2N
Me2N
MMe3
ð17Þ
<2002EJI3272>
(Ph3P)AuCl Cl–
THF, rt 85%
2
PH
Au
Me2N
Me2N
P
H
NMe2
NMe2
PHMe2N
Me2N
+
ð18Þ
<2001CC1208, 2002PS(177)1609>
W(CO)4(COD)
19%P
Ph2P
Cl Mes*P
Ph2P W(CO)4
Cl Mes*
ð19Þ
Several phosphaalkene transition metal complexes have been prepared by the reaction of freephosphaalkenes with Fischer carbene complexes. Thus, treatment of the phosphaalkene 39 within situ generated carbene complex anions results in stereoselective P–C coupling to form2-phosphabutadiene complexes 80 and 81 (Scheme 19) <1997AG(E)1095>.
When the chromium- and tungsten-[ethoxy(phenyl)methylene] complexes were combined withthe phosphaalkenes (Me2N)2C¼PR (R=But, TMS), the phosphaalkene complexes 82 and 84were isolated in 47–55% yield by fractioning crystallization. The complexes 83 and 85 were alsoformed, but they cannot be separated from the alkene 86 without decomposition (Scheme 20)<2001CEJ5401>.
676 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
Treatment of (Me2N)2C¼P-Fe(CO)2Cp* 24a with [(OC)5Cr¼C(OEt)Ph] led to the formationof [Cp*(CO)4Fe2] as the main product. The complex [Cp*(OC)2FeP{Cr(CO)5}¼C(NMe2)2] wasisolated in 10% yield <1998CEJ469>.
6.22.1.3.3 s3l5-Methylenephosphoranes, X2C¼P(¼Z)Y
Progress in the chemistry of �-bonded three-coordinate pentavalent phosphorus compounds hasbeen reviewed <1997CCR(158)275>. Since their discovery in 1974 hundreds of stable �3�5-phosphoranes have been synthesized and thoroughly investigated. Early work concentrated onpreparation of various structural types of monomeric Q¼P(¼Z)Y compounds. More recentlythe chemistry of functionalized �3�5-bis(ylene)phosphoranes has been developed, resulting both invaluable new reactions and synthetically useful, highly reactive polyfunctional �3�5-P reagents.
(i) From organodichlorophosphines
Experimental details for the preparation of [(TMS)2C¼]2PCl from MeOPCl2, Li(Cl)C(TMS)2and BCl3 are described in Synthetic Methods of Organometallic and Inorganic Chemistry<1996MI82>. A successful alternative approach to the title compound utilizes reactions of themonomeric bis(trimethylsilyl)methylenephosphines (vide infra).
The ferrocenyl-substituted bis(methylene)phosphorane 87 was synthesized in 52% yield byaddition of 3 equiv. of bis(trimethylsilyl)methylenecarbenoid to ferrocenyldichlorophosphine(Scheme 21). The X-ray structure of 87 shows some unusual structural features, which indicateconsiderable electronic interaction of the ferrocenyl group and the �3�5-phosphorane unit<1997JOM(541)237>.
i. BunLiii. (TMS)2C=PCl 39
M(CO)5
80, M = Cr (49%)
81, M = W (76%)
Et2O, –78 °CP
TMS
TMS(OC)5M
OEt
H
PhP
TMS
TMSEtO Ph
H(OC)5M
OEt
Ph
Scheme 19
+ +n-Pentane, –40 °C
82, R = But
84, R = TMS
83, R = But
85, R = TMS
86M = Cr, W
(OC)5MPh
OEt
NMe2
NMe2
Ph
EtOP
Ph
EtO RP
Me2N
Me2N R
M(CO)5 M(CO)5
(Me2N)2C=P–R
Scheme 20
2Li(Cl)C(TMS)2
THF-Et2O,n-C5H12
–100 °C
Li(Cl)C(TMS)2
87
52%Fe
Cl2P
Fe
P
TMSTMS
Fe
P
TMSTMS
TMSTMS
Scheme 21
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 677
(ii) From methylenephosphines and iminophosphines
The preparation of X2C¼P(¼Z)Y compounds by 1,1-oxidative addition reactions to dicoordi-nated phosphorus species is currently the method of choice in the synthesis of many types of�3�5-P derivatives. For example, Niecke and co-workers have successfully used this approach toprepare dichloromethylene(imino)phosphorane 89, which on lithiation with n-butyllithium gavethe iminophosphoranylidene carbenoid 90 (Scheme 22) <1994AG(E)982>. The application of thesame protocol to the phosphaalkene 91 led to the bis(methylene)phosphorane 92. However, theattempt to extend this strategy to prepare the dibromomethylene compound 93 by treatment of 91with bromoform and n-butyllithium produced only a 10% yield of the desired product. A moresatisfactory result was obtained in a modified procedure which involved the use of potassiumt-butoxide as base and afforded 93 in 91% yield. The oxidation of 91 into 94 by a chlorofluor-ocarbene moiety was achieved by addition of a mixture of 91 and CFCl3 to a titanium(0)suspension (Equation 20) <1995AG(E)1849, 1999JA5953>.
PMes*
TMS
TMSP
TMSTMS
Mes*X1
X2
i or ii or iii
92, X1 = X2
= Cl
93, X1 = X2
= Br
94, X1 = F, X2
= Cl
i. CHCl3/BunLi, THF/Et2O, –100 °C;
ii. CHBr3/ButOK, hexane, 0 °C; iii. TiCl4/LiAlH4/CFCl3, THF, –78 °C
91
ð20Þ
Treatment of 91 with dimethylsulfonium methylide cleanly afforded the bis(methylene)phos-phorane 95. Subsequent reaction of 95 with n-butyllithium proceeded via H/Li exchange to givethe phosphoranylidene ylide 96, which was isolated as highly air- and moisture-sensitive crystals(Scheme 23). The compound 96 may be easily transformed into new organometallic derivativeswith retention of the low-coordinate phosphorus center <1997JA12410>. A variation on thesame theme was also provided by the synthesis of the methylenephosphorane 98 containing a CH2
moiety at an sp2-hybridized P(V) center. While compound 98 is stable at ambient temperatures,it easily isomerizes by heating a toluene solution at �100 �C to give the correspondingmethylene(imino)phosphorane 99 (Scheme 24) <1997CC293>.
CCl4 /BunLi
THF, –105 °C
BunLi
8889 90
P
N
ClCl
Mes*
Mes*
P
N
LiCl
Mes*
Mes*
N PMes*
Mes*
45%
Scheme 22
Me2S=CH2 BunLi
9195 96
THF, 0 °CP
Mes*
TMS
TMSP Mes*
HH
TMSTMS
P Mes*
Li(THF)3H
TMSTMS
Scheme 23
678 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
Two convenient routes for the preparation of P-halo-bis[bis(trimethylsilyl)methylene]phosphor-anes 102–104 have been reported<1997S1013>. The reaction of phosphaalkene 100with 1 equiv. ofI2 resulted in a quantitative yield of the P-iodo derivative 104, which on treatment with AgCl gaveP-chloro-bis(methylene)phosphorane 102. In a second synthetic route, phosphaalkene 101 under-goes a fast rearrangement to the compound 102 when traces of 4-dimethylaminopyridine (DMAP)are present. Reactions of 102 with a little molar excess of bromo- or iodotrimethylsilane readily leadto bromo- and iodo-substituted compounds in truly excellent yields after work-up (Scheme 25).
The iminophosphine 97 reacts with iodine to form the methylene(imino)phosphorane 105.Upon subsequent treatment with AgCl, the corresponding chloro derivative 106 is obtained.Chlorine/bromine exchange in 106 with bromotrimethylsilane affords the bromo analog 107(Scheme 26) <1998EJI83>.
(iii) Derivatization via phosphoranylidene carbenoids
As mentioned in the previous section, phosphoranylidene carbenoids of the typeHal(Li)C¼P(¼Z)Y themselves represent valuable starting point for the synthesis of functiona-lized �3�5-methylenephosphoranes. They exhibit a pronounced carbanion character and remark-able stability even at elevated temperatures (�10 �C) due to the incorporation of the carbenoidiccarbon atom into a heteroallylic �-system <1999JA5953, 2002OM4919>. Thus, in typical carba-nion fashion, the phosphoranylidene carbenoid 90 reacted with chlorotrimethylsilane to affordthe silylated species Cl(TMS)C¼P(¼NMes*)Mes* <1994AG(E)982>. An analogous reactionwith formation of a protonated species was observed when Br(Li)C¼P[¼C(TMS)2]Mes* wastreated with water <2002OM4919>.
Me2S=CH2
THF, –40 °C
97 98 99
PN
HH
TMS
TMSTMS
Mes*P
TMS
TMS
N Mes*
TMSP N
Mes*
TMSTMSTMS
Scheme 24
AgCl
I2
THF, –78 °C 100%
DMAP (cat.) TMS–Br
103102101
100 104
100%
PTMS
TMS TMSTMS TMS
PTMS
TMS TMSCl TMS
P I
TMSTMS
TMSTMS
P Cl
TMSTMS
TMSTMS
P Br
TMSTMS
TMSTMS
TMS–I
Scheme 25
97 105
I2
THF, –40 °C
AgCl TMS–Br
THF, rt
106 107
P IN
TMSTMS
Mes*P Cl
N
TMSTMS
Mes*P Br
N
TMSTMS
Mes*P N
Mes*
TMSTMSTMS
Scheme 26
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 679
The stable LiF-carbenoid 108was accessible by treatment of the mixed halogenated bis(methylene)-phosphorane 94 with n-butyllithium. Metallation of the chlorofluoromethylene moiety proceededexclusively via Li/Cl exchange. Treatment of the carbenoid 108 with chlorotrimethylsilane at �78 �Cafforded the silyl-substituted bis(methylene)phosphorane 109 (Scheme 27) <2002OM4919>.
A synthetically valuable dilithiated species is assumed to be the intermediate in the reaction of93 with 2 equiv. of n-butyllithium. It allowed the synthesis of disubstituted bis(methylene)pho-sphoranes 95 and 110 that again represent interesting synthons (Scheme 28) <2002OM4919>.
6.22.1.4 Tetracoordinate Phosphorus Derivatives
The survey covers all types of isolable C,C-diheteroatom-substituted phosphorus ylides having aformal structure X1X2C¼PY3. For a treatment of materials published prior to 1994, readers arereferred to chapter 6.22.1.4 in <1995COFGT(6)677>. This topic also forms the subject of tworeviews <1996T1855, 1997RCR225> and a recent monography <B-1999MI1>.
There are four general methods for the production of the title compounds: (i) the directintroduction of a methylene moiety (X1X2C) into tervalent phosphorus compounds (PY3); (ii)the synthesis via the dehydrohalogenation or dehalogenation of corresponding phosphoniumsalts; (iii) the oxidative ylidation of tertiary phosphines containing a mobile hydrogen atom atthe �-carbon atom and behaving as CH acids; and (iv) the synthesis via a 1,2(C!P) halogen-otropic shift. Other methods for the synthesis of C-heterosubstituted phosphorus ylides aremainly restricted to examples including substitution reactions at the ylidic carbon atom.
6.22.1.4.1 Dihalosubstituted ylides, Hal2C¼PY3
The reaction of a halocarbene or carbenoid with a tertiary phosphine remains one of the mostimportant methods for the preparation of phosphorus ylides bearing two halogen atoms at theylidic carbon. Thus, the C,C-diidomethylenephosphorane 111 has recently been successfullygenerated from iodoform, triphenylphosphine, and ButOK. The ylide 111 can then undergo theWittig reactions in situ (Scheme 29) <1999TL8579>. Interestingly, however, the alkenes 112 couldnot be obtained when ylide 111 was generated from CI4 and Ph3P <1985CC296>.
It was recognized that the 1,2(C!P) chlorotropic rearrangement might make available ylidescontaining a dihalomethylene group. Thus, trichloromethylphosphine Cl3C–P(NMe2)2 can be con-verted into the P-chloro ylide Cl2C¼P(Cl) (NMe2)2 by boiling in dichloromethane <1996T1855>.Recently study of the chlorotropy of phosphine systems was extended to Cl3C–PCl2, which maypotentially undergo chlorotropic conversion to Cl2C¼PCl3. However, 35Cl NQR spectroscopy and
BunLi
THF, –78 °C
TMS-Cl
94 108 109
96%P Mes*
Li(THF)3
F
TMSTMS
P Mes*
TMSF
TMSTMS
P Mes*
ClF
TMSTMS
Scheme 27
2BunLi
THF, –78 °C
2RX
93 95, R = H
110, R = Me
P Mes*
TMSTMS
BrBr
P Mes*
TMSTMS
RR
PLi
TMS TMS
Li
Mes*
Scheme 28
680 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
MP2/RHF/6-31++ G(d,p) calculations indicate that the latter is thermodynamically less stable thanthe corresponding phosphine. According to the opinion of the authors, special experimentalconditions would be required to observe such conversion <2001MI163>.
6.22.1.4.2 Oxygen-, sulfur-, and selenium-substituted ylides, RE(X)C¼PY3 (E=O, S, or Se)
The development of phosphonium ylides bearing oxygen substituents at the �-carbon atom hasproceeded at a slow pace. This slow growth may have been due to the low thermal stability ofthese species. Ab initio quantum chemical investigations show that the presence of an oxygenatom at the ylidic carbon atom stabilizes singlet carbenes but not ylides. Therefore, oxygen-substituted methylenephosphoranes have an enhanced tendency to dissociate into carbenes andtertiary phosphines <1986CB1331>.
A new example of sulfur-substituted phosphonium ylides includes the compounds 114 and 115.The former has been isolated from the reaction of bis(diphenylphosphino)methane with hexa-fluorothioacetone dimer (HFTA) (Scheme 30). The first step of the reaction gives unstablecarbodiphosphorane 113 which decomposes at temperatures higher than �70 �C with the forma-tion of a complex mixture of products. However, when an excess of HFTA was used, only thesulfur-substituted ylide 114 was formed <2001EJI2377>. Synthesis of the ylide 115, bearingthioether and phosphoryl groups at the carbon atom has been accomplished by thiophilic reactionof ethyldiphenylphosphinite with phosphonodithioformate (Equation (21)) <1994PS(86)169>.
+ 2THF, 2 h, rt
+
115
P OEtO
EtO
SMeS P S
Ph
EtOPhP
P
MeSPh
Ph
OEtO
EtOEtOP OEt
Ph
Ph
ð21Þ
6.22.1.4.3 Nitrogen-, phosphorus-, arsenic-, and antimony-substituted ylides, R2E(X)C¼PY3
(E=N, P, As, or Sb)
Ab initio quantum chemical calculations carried out by Bestmann and co-workers<1986CB1331> predict instability for aminomethylenephosphoranes with respect to dissociationto a phosphine and a singlet carbene. Not surprisingly, efforts to obtain ylides of the type(R2N)2C¼PY3 were unsuccessful <1996T1855>. C-Amino-substituted phosphonium ylides areaccessible only when anion-stabilizing substituent (X) at the ylide carbon atom compensate forthe retarding influence of the nitrogen atom or when the latter is a part of aromatic or conjugatedsystem. Thus, the stable phosphoniotriazaphospholide 116 and several related cyclic productswere prepared from the products of the condensation of (TMS)2C¼PPh3 with PCl3 which serveas synthetic equivalents of a phosphoniophosphaethyne cation [Ph3P–CP]
+. For instance,
HCI3 + Ph3PRCHO
THF, rt
ButOK
THF, –78 °C 80%
R = Alk, Ar
PPh3I
I
I
I
R
111 112
Scheme 29
[(F3C)2C=S]2
Et2O, –70 °C
[(F3C)2C=S]2
50%
113 114
C PPPh
SPh
CF3
CF3Ph
SPh
F3C
F3C PPh
SPh
CF3
CF3P
SF3C
F3C
PhPh
Ph2P PPh2
Scheme 30
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 681
cycloaddition reactions of [Ph3P–CP]+X� (X=AlCl4, GaCl4 or TfO) with phenyl azide leads to
the zwitterionic phosphoniotriazaphospholide 116 and to the phosphoniotriazaphospholes 117.The former readily undergoes a cycloreversion yielding Ph3PCN2 as intermediate. Its cycloaddi-tion affords the remarkably stable diphosphoniodiazaphospholide chloride 118 as the finalproduct <1997CB89>.
116 117 118
NNN
N PPh3
NNN
P PPh3Ph+
NN
P PPh3Ph3P+
Cl–X–
Nitrilimine 119 has been used in the synthesis of the stable phosphorus ylide 120. Formally, thismethod includes a coupling reaction between Me3P and the carbenic form of the dipole 119(Equation (22)) <1997JOC292>.
+ Me3P
75%
+
119
C N N PR
MeRP
R
SR
PMe
MeMe
PN N
P RMe R
R
RS
CF3SO3–
CF3SO3–
R = Pr2Ni 120
+–
ð22Þ
The preparative chemistry of the highly reactive ylides bearing functionalized phosphorussubstituents at the ylidic carbon atom, and that of related cyclic compounds, has continued tobe an active area. Following earlier studies of the generation of phosphorus-substituted ylides bythe condensation of silyl ylides with chlorophosphines, chloroarsines, and chlorostibines, it hasbeen shown that reaction of silicon-substituted ylides with phosphorus trihalides gives rise toC-halophosphinyl ylides. Thus, the convenient procedure for the synthesis of ylides 121 and 122involves the condensation of trimethylsilyl ylides R(TMS)C¼PPh3 with PCl3. The ylide 121resulting from (TMS)2C¼PPh3 can react with a second mole of PCl3 to give 122 (Equation(23)). Interestingly, the bis(phosphinyl) ylides (Ph2P)2C¼PPh3, (ClPhP)2C¼PPh3 and(Cl2P)2C¼PPh3 (X-ray data reported) have analogous molecular structures. Details reflect thedifferent charge transfer from the ylide center to the phosphinyl substituents <1999ZN(B)1>. Itmay be also noted in passing that ylide 121 readily undergoes reduction with LiAlH4 to give theH2P-functionalized ylide H2P(TMS)C¼PPh3 <1998EJI381>.
PPh3TMS
R+ PCl3
–TMS–ClPPh3
Cl2P
R
121, R = TMS
122, R = PCl2
ð23Þ
The trimethylsilyl ylide (TMS)2C¼PPh3 reacts smoothly with 2 equiv. of AsCl3 to give thebis(dichloroarsinyl)methylenephosphoranes 124. If 1 equiv. of AsCl3 is used, the substitutionreaction stops at the dichloroarsinyl ylide 123, which slowly loses a further molecule ofchlorotrimethylsilane leading to the cyclic ylide 125. For a structural proof 125 was convertedto its bis(diphenylphosphinyl) derivative 126. If performed in pyridine, the reaction of equimo-lar amounts of (TMS)2C¼PPh3 and AsCl3 leads to a tetramer 127 (Scheme 31)<2000CEJ3531>. Likewise, 2,4-diphosphoranediyl-1,3-diphosphetanes are obtained from(TMS)2C¼PPh3 and PCl3 or PBr3 <1997CB1519>.
The versatility of the substitution reactions is also demonstrated by the synthesis of highlyfunctionalized ylide 128. It subsequently gets involved in an intramolecular reaction between theremaining PCl2 group and the phenyl ring to give the cyclic ylide 129. Other C-(dichloropho-sphinyl) ylides, e.g., 130, have been obtained by the carbodiphosphorane route (Scheme 32)<1997JOM(529)87, 1996ZN(B)773, 1995CB379>.
682 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
Ylides 131 (R=Ph, 3-MeC6H4) react with 122 both at their 1- and ortho-position to yield thediphosphatetralines 132. The two P–Cl functions in the molecules 132 differ decisively in theirspontaneous dissociation in a polar medium, and in their oxidation by elemental sulfur. WithGaCl3 dicationic 1,3-diphosphanaphthalenes 133 are formed, which represent a novel �10 system(Scheme 33) <1996ZN(B)773>. Finally, the ylidediyl halophosphine oligomers, (XPCPPh3)n(X=Cl, Br, n=2–4), were prepared from (TMS)2C¼PPh3 via (X2P)(TMS)C¼PPh3 and(X2P)2C¼PPh3 <1995AG(E)1853>.
AsCl3 AsCl3
C6H6, rt 86%
Cl–
123 124
126125127
AsCl3/Py –TMS–Cl
i. HCl
ii. 2Ph2P(TMS)
AsCl4–
PPh3TMS
TMSPPh3
TMS
Cl2AsPPh3
Cl2As
Cl2As
As
AsAs
AsCl
PPh3
ClPPh3
Ph3P
PPh3Cl
+
As
AsPh3P
Cl
PPh3
Cl
As
AsPh3P
Cl
Cl
PPh3
H
+
Scheme 31
+P PPh3Ph3P
Ph
Cl
Cl2P
P PPh3Ph3P
PPh3
Cl
Cl2P
Ph3P=C=PPh3
Cl–
P
PPh3P PPh3
Cl
130 129
128
–TMS–Cl
–HCl
+
+
Cl–
PPh3Ph
TMSPPh3
Cl2P
Cl2P
122
Scheme 32
P
P
PPh3
PPh3
R1
R2
Cl
Cl
+P
P
PPh3
PPh3
R1
R2
+
+
2GaCl4–
2GaCl3
–TMS–Cl–HCl
122132 133
131
131: R = Ph (a), 3-MeC6H4 (b)
132, 133: R1 = R2
= H; R1 = H, R2
= Me or R1 = Me, R2
= H
PPh3Cl2P
Cl2PPPh3
TMS
R
Scheme 33
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 683
The condensation of dichlorophosphinyl-substituted ylides Cl2P(R)C¼PPh3 with (TMS)2S and(TMS)2Se has been used to effect the formation of the first stable monomeric phosphorusmonochalcogenides 134. Ylides 134 are stabilized by a high contribution of the zwitterionicresonance forms, which follows both from the NMR and from an X-ray structure determination.Alkylation of 134 resulted in alkylchalcogeno(ylidyl)phosphenium salts 135 <1995CB1207>. Theinitial product of condensation of Cl2P(TMS)C¼PPh3 with (TMS)3P is a diphosphene 136, but,at ambient temperatures, dimerization to an ylide-substituted cyclotetraphosphine 137 occurs(Scheme 34) <1997CB1801>.
A carbene route has also received further study. Thus, the stable carbenes R2P(TMS)C haverecently been used as reagents for the ylide synthesis. Instantaneous and quantitative formationof ylides 138 occurred when 1 equiv. of phosphine was added at 0 �C to a solution of the carbene[(c-Hex)2N]2P(TMS)C] in pentane <1999AG(E)3727>. As a further development of this workthe synthesis of phosphinyl ylides 139 has been achieved as shown in Scheme 35<2002JA2506>. These same workers discovered that treatment of the stable [bis(diisopropyl-amino)phosphino](silyl)carbene with bis(diisopropylamino)phosphenium triflate leads to theformation of the adduct 140. The synthesis of ylide 141 was achieved by the reaction of 140with methyl magnesium bromide (Scheme 36) <2000SCI(289)754>.
+
R = Et
(TMS)2E
PP
PP
TMS
TMS
134 135
136
137
(TMS)3P
+ X–
1/2
R = Alk, Ar, or TMS; E = S or Se; X = TfO, I, Br
PPh3R
Cl2PPPh3
R
PEPPh3
Et
PEMe PPh3
Et
PEMe
PPh3TMS
PPTMS
R = TMS
PPh3
TMS
Ph3P
TMS
X–MeX
Scheme 34
R1R2PCl
138a–138e
139a–139d
138: R = c-Hex2N; Y3P = Me3P (a), Et3P (b), Me2PhP (c), MePh2P (d), Ph3P (e)
139: R1R2 = –N(But)SiMe2N(But)– (a), R1
= R2 = But (b), R1 = Pr2N, R2
= Ph (c), R1 = R2
= Ph (d)
O2Y3P
Pentane, 0 °CPY3
TMS
R2P
TMS
R2PPY3
TMS
R2PO
P2R1RP
TMS
Cl
RR
i
Scheme 35
684 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
The interaction of diphosphoryl-substituted ylide [Ph2P(O)]2C¼PPh3 (L) with phosphoruspentafluoride in acetonitrile has been studied in detail. The reaction gave chelated ylide cis-PF4L
+PF6� as shown by 19F and 31P NMR spectral data. Small amounts of linear adduct
(PF5)2L were also observed <1997DOK(352)352>.
6.22.1.4.4 Silicon-, germanium-, and boron-substituted ylides, R3E(X)C¼PY3 (E=Si or Ge)and R2B(X)C¼PY3
There are few reports in the literature on the synthesis of silicon- and germanium-substitutedphosphorus ylides via the dehydrohalogenation of corresponding phosphonium salts<B-1998MI238, 1997ZN(B)674, 1996T1855>. These reactions generally proceed in high yieldsand tolerate the presence of a broad range of functional groups.
The ability of phosphinomethanides [R2P–C(X)Y]�Li+ to react with certain electrophiles viathe phosphorus atom has been used for the preparation of new types of silyl ylides. As anexample, PhSiCl3 reacts with 142 to give a fluxional, pentacoordinate silicon compound 143,which slowly rearranges to the tetraheteroatom substituted methane derivative 144 and further tothe ylide 145 (Scheme 37). An analogous ylide (ButCl2Si) (TMS)C¼PMe2–PMe2 is obtained fromButSiCl3 and 142 instantaneously <1994ZN(B)1798>. Other reactions of lithium phosphino-methanides with polyfunctional chlorosilanes yield novel five- and six-membered heterocycles146–150 with Si and P ring members <B-1994MI187, 1995AG(E)557, 1995JOM(501)167,1997JOM(529)151>.
PMe2P
P
PMe2PP
P
P PP
Me MeTMS TMS
TMS TMS
MeMeMe
Me
MeMe
MeMe
SiMe2P
SiMe2P
Ph Ph
Ph Ph
PMe2
146 147 148 149 150
PMe2P
TMS
Si
MeMe
PMe
PMe2
RTMS
PMe2
Si
Me2Si
MePhTMSTMS
TMS
PP
TMS
RR
R2P+ CF3SO3–
MeMgBr
R = Pr2Ni
TMS
R2P
RR P
TMS
R2PR
R
Me
CF3SO3–
+
140 141
Scheme 36
PhSiCl3 + Li[C(PMe2)2(TMS)]–LiCl
142
143144
145
SiTMS
PMe2
Cl
ClPh PMe2
PSi
PTMS
Me Me
MeMe
PhCl
Cl
PMe
MePMe2
Si
TMS
ClCl
Ph
Scheme 37
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 685
The reactions of ECl3 (E=P, As, Sb) with 3 equiv. of the phosphinomethanide 151 in all three casesleads to element–phosphorus bond formation and the first element–tris(P-ylide) derivatives 152–154 areobtained, along with some byproducts. For BiCl3, only the bisylide 155, besides elemental bismuth, isobtained. No Bi-containing compounds could be identified (Scheme 38) <1997JOM(529)151>.
The reaction of dichlorophosphines RPCl2 (R=Me, Ph, But, Cy2N) with 151 is dependent on thenature of R and leads, at least in part, to some unexpected products. As in the reactions of ECl3(E=P, As, Sb), P�P bond formation is also observed in the reaction of MePCl2 with 2 equiv. of 151.The bisylide 156 is obtained in good yield, but traces of 155 are also formed. If the steric demand of Rin RPCl2 is increased, i.e., by reacting PhPCl2 with 151, in addition to 155 and 157, a new couplingproduct, the diphosphine bridged bisylide 158, is formed (Scheme 39). With further increase inthe steric demand of R, i.e., with ButPCl2, only (ButP)3 and (ButP)4 were obtained. An analogousresult is observed in the reaction of ButPCl2 with LiC(PMe2)2(TMS) <1997JOM(529)151>.
Among the C,C-diheterosubstituted phosphonium ylides the only well-characterized boron-substituted ylide is (MeO)2B(TMS)C¼P(NR2)2OMe prepared by the reaction of a stable carbenewith B(OMe)3 <1994AG(E)578>.
6.22.1.4.5 Metal-substituted ylides, LnM(X)C¼PY3
Compared with the rich chemistry of transition metal ylide complexes, metallated phosphorus ylides,which formally arise from substitution of a hydrogen atom at the ylidic carbon by a metal atom andfeature a dicarbanion center, have been investigated only briefly <1996T1855, 1994CRV1299>.
Recently, reaction of the stable phosphinyl(silyl)carbenes with organolithium compounds wasproposed as a new route to the �-(lithiomethylene)phosphoranes <1999AG(E)678>. Indeed,addition of 1 equiv. of n-butyllithium to a solution of carbene R2P(TMS)C in pentane at
ECl3 + 3LiC(PMe2)(TMS)2
TMS
TMSPMe
MePMe
Me
TMS
TMS+ Bio
E = Bi
Et2O, –78 °C
Et2O/
E = P, As, Sb
151
152, E = P
153, E = As
154, E = Sb
155
Me2P E PMe2
PMe2 C(TMS)2
C(TMS)2
(TMS)2CTHF, –78 °C
Scheme 38
2LiC(PMe2)(TMS)2
+
156
157 158
MePCl2
PhPCl2
Et2O, –78 °C
Et2O, –78 °C
PP
PPh
PhPMe
Me
TMS
TMS
TMS
TMS
Me
Me
PhP
P PMe
TMS
TMSMe
MeTMS
TMSMe
MeP
P PMe
TMS
TMSMe
MeTMS
TMSMe
151
Scheme 39
686 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
�78 �C instantaneously and quantitatively led to the desired ylide 159. Metallated ylide 159 ishighly moisture sensitive and is easily transformed into the ylide TMS(H)C¼PR2Bu
n. It alsoreacts with electrophiles such as MeI and Ph2PCl to give the corresponding ylides 160 and 161,respectively (Scheme 40).
The gallyl-substituted ylide Me2Ga(TMS)C¼P(NR2)2Me is also accessible by reaction of astable phosphinyl(silyl)carbene with GaMe3 <1994AG(E)578>.
6.22.1.5 Tetracoordinate Arsenic, Antimony, and Bismuth Derivatives
In comparison with C,C-diheterosubstituted phosphonium ylides (X1X2C¼PY3), the area ofrespective arsenic, antimony, and bismuth derivatives is poorly explored <B-1994MI657>. Thismay have been due to the lack of general methodology for the synthesis of suitable precursors andin part to the low thermal stability of compounds bearing a formal EV¼C double bond (E=As,Sb, Bi). The difference between phosphonium ylides and their heavier analogs is commonlyascribed to the less efficient overlap between the sp2-C orbitals and the larger and more diffuse4d orbitals of arsenic, stibium, and bismuth. Therefore, contribution of the ‘‘covalent’’ canonicalform should become smaller as compared with the corresponding phosphonium ylides. Arsonium,and especially stibonium and bismuthonium ylides, are commonly less stable than their phos-phorus counterparts and have a tendency to decompose both in solution and in solid state unlessthere is electronic stabilization. A significant increase in stability of the ylides X1X2C¼EY3, isobserved, however, if electron withdrawing groups (X) such as carbonyl or sulfonyl are conju-gated with the ylidic carbon atom <1998JOM(557)37, 1996BCJ2673>.
The methods available for the synthesis of arsonium, stibonium, and bismuthonium ylides arenearly all analogous to methods used for the corresponding phosphonium ylides.
6.22.1.5.1 C,C-Diheterosubstituted arsonium ylides, X2C¼AsY3
Bis(sulfonyl)methylenetriphenylarsoranes, (RO2S)2C¼PPh3, remain only one type of well-char-acterized and studied C,C-diheteroatom-substituted arsonium ylides. No information aboutsynthesis of other C,C-diheterosubstituted species is available since the publication of chapter6.22.1.5.1 in COFGT (1995) <1995COFGT(6)677>.
6.22.1.5.2 Stibonium and bismuthonium ylides bearing heterosubstituents,X2C¼EY3 (E=Sb or Bi)
Yagupolskii and co-workers have described synthesis of a new bis(trifluoromethylsulfonyl)-substituted stibonium ylide <1994ZOB1277>. Treating Br2C(SO2CF3)2 with 3 equiv. of tributyl-stibine results in the formation of stable stibonium ylide 162 (Equation (24)). The same group hasalso shown that treatment of sodium derivatives of the corresponding bis(sulfonyl)methanes withPh3BiCl2 gives rise to the bismuthonium ylides 163 (Equation (25)). From the NMR spectra,zwitterionic canonical structures containing Bi+–C� or Bi+–C¼S–O� units may be assumed<1994JFC75>.
BunLi
Pentane, –78 °C
159 160, R1 = Me
161, R1 = Ph2PR = c-Hex2N
>92%
MeI or Ph2PCl
R2P
TMSP P
Li
TMS
R
Bun
RR1
TMS
R
Bun
R
Scheme 40
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 687
++ 3Bu3
nSb50%
162
CF3O2S
Br
Br
CF3O2SSbBu3
n
CF3O2S
CF3O2S
X–
ð24Þ
>90%
Rf = F3C, n-C4F9, OCH2CF2CF2H
+ Ph3BiCl2
163
RfO2S
Br
Na
RfO2S
+–BiPh3
RfO2S
RfO2S
X
ð25Þ
The synthesis, characterization, and solid-state structure are described for a reversed ylide 164,derived from 1,3-dimesityl-4,5-dichloroimidazol-2-ylidene and tris(trifluoromethyl)antimony(Equation (26)) <1999ZAAC(625)1813>. According to X-ray data, the ylide 164 retains reactant-like geometries for both the component fragments and is thus predisposed to facile cleavageof the carbene–antimony bond. Variable temperature solution NMR spectroscopic studies suggestthat the carbene fragment readily dissociates from antimony center at temperatures as low as�95 �C.
+ (F3C)3Sb+–
164
92%Sb(CF3)3
N
N
Mes
Mes
Cl
Cl
N
N
Mes
Mes
Cl
Cl
X ð26Þ
6.22.2 FUNCTIONS CONTAINING A DOUBLY BONDED METALLOID
6.22.2.1 Tricoordinate Silicon and Germanium Derivatives
Progress over the past decade in the chemistry of p�–p� systems involving carbon and the heaviergroup 14 elements (Si, Ge) has been reviewed <1996MI71, B-1996MI367, B-1998MI857,1998CCR565, 1999MI113>. The most readily available reaction pathways used to produceC,C-diheterosubstituted sila- and germaethenes are: (i) 1,2-elimination of a salt (LiY) from�-lithiated silanes or germanes R2E(Y)–C(Li)R2 carrying a good leaving group (Y) on the elementatom, (ii) 1,2-(Si�C) silyl carbene–silaethene rearrangement, and (iii) coupling between a silyleneor germanium(II) derivative and a nucleophilic carbene.
6.22.2.1.1 Diheterosubstituted silaethenes, X2C¼SiY2
Full details have appeared of studies of the formation, detection, and stabilization of the short-lived silaethene 167 <2000JOM(598)292, 2000JOM(598)304>. This compound is formed byreaction of trisilylmethanes 165 with alkali metal organyls or silyls via intermediates 166 and, inthe absence of trapping agents, reacts with 166 to give the compounds 168, which in turneliminate MX under formation of the 1,3-disilacyclobutane 169. In the presence of an excess oforganyl or silyl azides, which act as very active trapping reagents for the silaethene, the [3+2]-cycloadducts 170 are formed (Scheme 41). Direct detection of the silaethene 167 has beenaccomplished by laser-flash photolysis of Me3SiMe2SiC(N2)SiMe3 <2001OM5707>.
Bromotrisilylmethanes 171–173 have been used as sources of the corresponding isomericsilaethenes with six Me and two Ph substituents. Phenyllithium converts the above compoundsby Br/Li-exchange to lithium organyls, which in ether solution are in equilibrium with unsatu-rated silicon derivatives. The intermediacy of the silaethenes has been established by their trap-ping with 2,3-dimethylbutadiene <1996JOM(524)147>.
688 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
171 172 173
R = TMS, R1 = PhMe2Si, R2
= Ph2MeSi
Si
Br
Ph
MeBr
RR1 Si
Br
Me
MeBr
RR2 Si
Br
Me
MeBr
R1
R1
Dehalogenation of the sterically overloaded trisilylmethanes R*(TMS)BrC–Si(X)Me2 has beenexploited for the synthesis of silaethene R*(TMS)C¼SiMe2 (R*=But3Si). Reaction ofR*(TMS)BrC–Si(X)Me2 (X=F, TfO) with PhLi leads to R*(TMS)LiC–Si(Ph)Me2, whileR*(TMS)BrC–Si(F)Me2 reacts with But3SiNa to give R*(TMS)NaC–Si(F)Me2. The latter com-pound transforms in THF in the presence of Me3SiCl into the corresponding silaethene, whichmay be trapped by reactants like MeOH, Me2CO, or 2,3-dimethylbutadiene. It follows from thisstudy that the metastability of compounds (ButnMe3�n Si) (TMS)C¼SiMe2 with an increasingnumber of But groups pass through a maximum for n=2 <1997JOM(531)47, 1996CB471>.
Using a new synthetic pathway, Oehme and co-workers recently succeeded in preparing avariety of new C,C-disilyl-substituted silaethenes. They observed that dichloromethyltris(tri-methylsilyl)silane reacted with an excess of organolithium reagents RLi (R=Me, Bun, Ph)under substitution of the two chlorine atoms and a complete reorganization of the wholesubstitution pattern of the molecule to produce silanes of the type (TMS)2CH–Si(TMS)R2
<1999OM1815>. As shown in Scheme 42, in this process the transient silaethenes 174 and 175occur as intermediates, which are trapped by the organolithium reagent present in the reactionmixture, and the reaction affords 176 as the end product after aqueous workup. However, if, forthe reaction with Cl2CHSi(TMS)3, an organolithium reagent is chosen with a group R, which,when introduced at the silicon atom, provides sufficient stabilization of a silaethene systemthrough an intramolecular donor–acceptor interaction, it possible to halt the reaction at thisstage and to isolate a silaethene. This was achieved, for example, in the reactions ofCl2CHSi(TMS)3 with suitably functionalized organolithium compounds in the molar ratio 1:2,
Me2SiSiMe2
TMSTMS
TMSTMS
RM
–RBr
–MX +MX
165 166
167
170169
168
RM = BunLi, PhLi, (TMS)2CHLi, Bu3SiNa; X = F, Br, PhOt
166
R1N3
Si
X
Me
MeBr
TMSTMS Si
X
Me
MeM
TMSTMS
Si
Me
Me
TMS
TMSSi Si
X
Me
MeTMS
MTMS
Me
Me
TMS
TMS
NN
SiMe2
NTMS
TMS
R1
Scheme 41
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 689
which led to the isolation of intramolecularly donor-stabilized silaethenes 177–179<2000AG(E)1610, 2001JOM(621)261, 2001CEJ987>. By the use of sterically congested organo-lithium derivatives, the nucleophilic addition of RLi to the C¼Si bond can also be prevented andkinetically stabilized silaethenes obtained. Thus, silaethene 180 was synthesized by the reactionof Cl2CHSi(TMS)2Ph with 2,4,6-triisopropylphenyllithium. Similarly, silaethenes 181 and 182were prepared from Cl2CHSi(TMS)3 and 2,4,6-triisopropylphenyllithium or 2-t-butyl-4,5,6-tri-methylphenyllithium (Scheme 43) <2001EJI481>.
Si
TMS
Me2N
Si
TMS
Me2N
Si
TMS
Me2NNMe2
177 178 179
TMS
TMS
TMS
TMS
TMS
TMS
Ottosson and co-workers <2002OL1915> have used Brook’s procedure to generate transientsilaethenes R2N(TMS-O)C¼Si(TMS)2 (R=Me, Ph). Formation of the latter through photolysisof the compound Me2NC(O)Si(TMS)3 was attempted before and found to be unsuccessful sinceno reaction occurred upon long irradiation <1991JOM(403)293>. In a modification of this
Si
TMS
TMS
TMSCl–LiCl
SiTMS
TMS
D
TMS
Si
TMS
TMS
TMS
Cl
ClLi
SiTMS
TMS
TMS
Cl
–LiCl
RLi
–RH
RLi
Si
R
TMS
TMS
ClLi
TMS
Si
TMS
TMS
TMS
Cl
Cl
–LiCl
SiTMS
R
TMS
TMS
SiTMS
TMS
R
TMS
R
for RLi = MeLi,BuLi, PhLi
i. RLiii. H2O
174
175
176
for RLi = Li–D
Scheme 42
690 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
method, the silaethenes have been prepared by thermolysis of the silylamides R2NC(O)–Si(TMS)3. The short-lived silaethenes are trapped with 2,3-dimethylbutadiene to quantitativelyyield only one of the possible diastereomers of the cyclic allylsilanes. Ab initio calculations revealthat the silaethene Me2N(TMS-O)C¼Si(TMS)2 is characterized by reversed C+–Si� bond polar-ization and features a carbon–silicon single bond and a pyramidal silicon atom.
Related carbene–silylene adduct 183 in which the C�Si bond is best formulated as beingelectrostatic in nature, with the carbene moiety as electron donor and the Si(NN) fragment asacceptor, has been prepared according to Scheme 44. The compound 183 is monomeric, with thethree-coordinate C and Si atoms in an almost planar (C) or pyramidal (Si) environment<1999CC755, 2000JCS(D)3094>.
6.22.2.1.2 C,C-Diheterosubstituted germaethenes, X2C¼GeY2
The C¼Ge bond is of low intrinsic thermodynamic stability, so that stable germaethene deriva-tives all contain sterically bulky substituents at both germanium and carbon <1998CCR565>.Uncomplicated germaethenes exists only as transient species. The methods available for theirsynthesis are nearly all analogous to methods used for the corresponding silaethenes<2000JOM(598)292, 2000JOM(598)304>. The most established process for the generation oftransient C,C-diheterosubstituted germaethenes is based on the formation of the C¼Ge bondby the salt elimination method. For example, germaethene (TMS)2C¼GeMe2 is formed as ashort-lived intermediate by reaction of (TMS)2BrC–GeMe2X with RLi via (TMS)2LiC–GeMe2X(X=electronegative substituent, R=organyl) <2000JOM(598)304>. Interestingly, thermolysisof 184 at 100 �C in the presence of propene, butadiene, 2,3-dimethylbutadiene or isobutene leadsto ene reaction product and/or [4+2]-cycloadducts of the germaethene 186. The formation ofthese trapping products proves the intermediate existence of a compound with Ge¼C bond andindicates that the equilibrium between 185 and 186 lies at the side of germaethene (Scheme 45)<1996JOM(511)239, 1996JOM(519)107>.
Si TMS
R1
TMS
–LiCl
R2Li
–R2Cl, –LiCl
180, R1 = Ph
181, R1 = TMS
182
Cl
ClSi
R1
R2
Cl
TMSLi TMSSi
R1
TMS
Cl
TMS R2LiSi
R1
R2
TMS
TMS
Si
R1TMS
TMSSi
TMS
TMS
TMS
Scheme 43
NH
NH
R
R
Cl2CS
N
NS
R
R
C8K
N
NR
R
NSi
NR
RSi
N
NN
N
R
R R
R
Pentane, –25 °C
183
+–
83%
Scheme 44
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 691
Recently, the [4+2]-cycloadduct of (TMS)2C¼GeMe2 and anthracene has been proposed as a‘‘store’’ for the germaethene <2000CJC1412>. Adduct 188 can be prepared by reaction of anexcess of anthracene in benzene with germaethene precursor 187. Above 100 �C it decomposesreversibly via thermal cycloreversion into (TMS)2C¼GeMe2 and comparatively unreactiveanthracene. The half-life of the anthracene adduct in the presence of 2,3-dimethylbutadiene(DMB) in t-butylbenzene on thermolysis at 130 �C is found to be 12 h. In the absence of DMB,thermolysis leads to the dimer of the germaethene (Scheme 46).
Among the stable C,C-diheterosubstituted germaethenes the only well-characterized and stu-died compounds are adducts obtained from the germylenes and the free carbenes. New examplesare the germaethenes 189 and 190 prepared by reactions between the appropriate germanium(II)compounds and nucleophilic carbenes <1993IC1541, 2000JCS(D)3094>. Related carbene–germy-lene complex 191, in which the ring represents a diborylcarbene system, is also readily availablefrom its factors, the kinetically stable diarylgermylene and Berndt’s carbene <1999HAC554>. Itshould be made clear that the structures of 189 and 190 are best described as a Lewis base–Lewisacid adducts in which the newly formed C�Ge bond is not a true double bond but rather highlypolarized C+�Ge� bond. In contrast, the X-ray structure analysis as well as NMR data ofcryptodiborylcarbene adducts 191 suggest some significance for the ylide resonance formula oftype C��Ge+, expected from the interaction between an electrophilic carbene and a nucleophilicgermylene <1987AG(E)798, 1999HAC554>.
Si But
F
But
Me3GeMe3Ge
Li
100 °C
80% 77%
184 185
186
–LiF But
But
Me3Ge
Me3Ge
GeSiMeBut
2
GeMe3
Me
Me
Ge SiMeBut2
GeMe3MeMeGe
SiMeBut2
Me
MeGeMe3
Scheme 45
Ge
Me
OPh
MeTMS
TMSLi
Ge TMSMe
–PhOLi
t-BuC6H5
Me2GeGeMe2
TMSTMS
TMSTMS
100 °C
187
188
130 °C
GeMe2
TMSTMS
Ge
Me
Me
TMS
TMS
TMSMe
Scheme 46
692 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
N
NGe
B
BGe
TMS
TMS
But
But
189 190, R = ButCH2 191, R = 2-But-4,5,6-Me3C6H
N
N
R
R
Mes
MesI
IR R
GeN
NR
R
+–
+–
Phosphino(silyl)carbene 192 reacts with germylenes affording the C-germylphosphaalkenes 194(Scheme 47). It is reasonable to postulate the primary formation of the germaethenes 193, whichwould undergo a subsequent 1,3-shift of Me2N group from phosphorus to germanium atom toproduce compounds 194. The instability of 194 is not surprising whatever the polarity of theC¼Ge bond, since the phosphorus center is not efficient enough to stabilize an adjacent positivecharge and destabilizes a negative charge <1992IC3493>.
Okazaki and co-workers prepared the first stable germaketenedithioacetal 197 by treatment ofovercrowded diarylgermene 195 with carbon disulfide. The formation of 197 can be reasonablyinterpreted in terms of the intermediacy of thiagermiranethione 196, as shown in Scheme 48.Exclusive formation of 197 without any 1:1 addition product, even in the presence of an excessamount of carbon disulfide, implies a much higher reactivity of the thiocarbonyl unit of 196toward germylene 195 than that of carbon disulfide <1995CC1425, 1996CL695>.
6.22.2.2 Functions Incorporating a Doubly Bonded Boron
Among organoboron compounds many C,C-disilyl-substituted doubly bonded molecules havenow been synthesized, such as methyleneboranes 198, 2-borataallenes 199, and boriranylidene-boranes 200. Stable methyleneboranes are obtained only when the C¼B double bond is stericallyshielded by large substituents. In addition, electronic stabilization is necessary either throughformally nonbonding electron pairs on the atoms directly adjacent to the dicoordinated boronatom or through electropositive substituents at the position � to the dicoordinated boron atom.
+ GeR247–68%
192 193 194
R = (TMS)2N or Mes*NH, Tmp = 2,2,6,6-tetramethylpiperidino, Mes* = 2,4,6-Bu3C6H2 t
THF, rtGe
R
R
TMS
PTmp
Me2N
TMS
PTmp
Me2NGe
R
R
TMS
PTmpNMe2
Scheme 47
Ge S C S
Tbt
Ge
Tip
S
S
Tbt
Ge
Tip
S
S GeTbt
Tip
–THF, rt +
195 196
GeS
GeS
46%
197
Tbt = 2,4,6-[(TMS)2CH]3C6H2, Tip = 2,4,6-Pr3C6H2i
Tip
Tbt
GeTip
Tbt Tbt
Tip
CS2 195
Tip
Tbt
+–
Scheme 48
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 693
Thus in amino-substituted methyleneboranes 198 (Y=R2N) or 2-borataallenes 199, the electrondeficiency at the dicoordinated boron atom is relieved through �–� delocalization of the formallynonbonding electron pairs on the neighboring atom. In nonclassical methyleneboranes 200, theelectron-deficient center at the dicoordinated boron atom forms nonclassical three-center, two-electron (3c–2e) bonds with neighboring � bonds.
BY
B–
M+
198 199 200
X
X
X
X R
R BR
X
XB R
There are a number of specialized methods for the formation of X2C¼B functions which,however, do not seem to have general applicability. For further details a comprehensive review onthis subject should be consulted <1996MI355>.
6.22.2.2.1 Methyleneboranes, X2C¼B-Y
Various synthetic pathways for the formation of X2C¼BY species are outlined in Scheme 49<1993AG(E)985>. The simplest route involves a 1,2-elimination reaction at organoboraneshaving functional substituents X at carbon and Z at boron atom which combine to a thermo-dynamically favored leaving molecule XZ, e.g., Me3SiF. This is currently the method of choice inthe synthesis of C,C-disilyl-substituted methyleneboranes of the general formula (TMS)2C¼BY<1989CB1057>. Methods involving either the cleavage of B�C single bonds in (borylmethylene)–boranes or reactions of borataalkynes with electrophiles have also proved sufficiently effective<1993AG(E)985, 1991AG(E)594>. Finally, the thermal cycloreversion of 1,3-diboretanes and1,2-dihydroboretes is of considerable potential for the generation of methyleneboranes<1990AG(E)401>.
Li+
BCB
B C B
2Li+
TMS TMS)
BTMS
TMS
BY
BY
Z
–
Cycloreversion
Elimination (–XZ) Reactions with electrophiles
(+E+)
Cleavage of C–B bond
– –Reductiveelimination
Reductivecleavage
(–
X
XX
X
X
BB
B
B Cl
Cl
Scheme 49
694 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
The organic chemistry of boriranylideneboranes 200, obtained by Berndt and co-workers<1993AG(E)985> in the early 1980s through reductive elimination and rearrangement of thediborylalkenes has been extensively studied and is characterized by cleavage of bonds in the three-membered ring and migration of substituents <1995AG(E)1111, 1997AG(E)1469>. These speciesseem to be valuable starting materials for the synthesis of new type of heterosubstituted methy-leneboranes. Thus, the boriranylideneboranes 200a and 200b add B2Cl4 under cleavage of theSi2C�B bond to yield the (borylmethylene)boranes 201 in which three boron atoms are bonded toa methylene carbon (Equation (27)) <2001EJI387>. Reaction of the t-butyl derivative 200c with[Co(Cp)(C2H4)2] provides the metalacycle 202 featuring the metal-substituted C¼B double bond(Equation 28) <1998CEJ44>.
B2Cl4
Hexane, –85 °C 33–50%
R = Dur (a), Mes (b)
200a, 200b
BR
TMS
TMSB R B
B
B
RCl
RCl TMS
TMSBCl2
201
ð27Þ
Co
BB
But
[Co(Cp)(C2H4)2]
Hexane, reflux, 0.5 h
202
200c
BBut
TMS
TMSB But
TMS
TMS
But ð28Þ
6.22.2.2.2 2-Borataallenes, [X2C¼B¼CY2]�
Among possible synthetic strategies for 2-borataallenes, thermally induced isomerization ofC-borylboriranide 203 prepared from 200a by reaction with phenyllithium <1992AG(E)1238>or 2-boryl-1,3-diboretanides 205 accessible from the reaction of 204 with t-butyllithium<1990AG(E)1030> play an important role. In the last case, authors suggest the 1-bora-3-bor-atabutadiene as an intermediate, whose transformation into 2-borataallene requires a 1,3-migra-tion of an aryl group from the tri- to the dicoordinated boron atom. Reductive dimerization ofthe methyleneborane 198a has also been used in the synthesis of borataallenes (Scheme 50)<1990AG(E)1030>.
The 1-boryl-2-borataallenes react with electrophiles to form the (borylmethylene)boranes<1993AG(E)985>.
6.22.3 FUNCTIONS INCORPORATING A DOUBLY BONDED METAL
For the purpose of this survey, the above functions will be defined as the species of the formulaX1X2C¼MLn (X1, X2=heteroatom substituents), which formally contain a double bondbetween carbon and metal. Until 1990s, apart from the well-studied transition metal–dihalocar-bene complexes, there was comparatively little information on compounds involving C¼Mbonding between three-coordinate diheterosubstituted carbon and metal <1995COFGT(6)677>.The situation has changed recently. A breakthrough was the isolation of the first free N-hetero-cyclic carbene (NHC) by Arduengo and co-workers <1991JA361>. Since then NHCs and relatedacyclic diaminocarbenes have become accessible as ‘‘bottle-able compounds’’ and their inorganicand organometallic chemistry has gained enormously in versality and depth <1997AG(E)2162>.Numerous new varieties of diheterosubstituted carbene complexes were reported within a shortperiod of time. The reviews by Herrmann <2001MI1, 2002AG(E)1290>, Arduengo<1999ACR913>, Bourissou and co-workers <2000CRV39>, and Enders and Gielen<2001JOM(617/618)70> provide a valuable survey of the literature up to 2002.
In comparison with transition metal–carbene complexes, the area of respective molecule withcarbon–Main Group metal double bond remains rather poorly explored <1998CCR565,2001MI621>.
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 695
6.22.3.1 Transition Metal–Carbene Complexes
6.22.3.1.1 N-Heterocyclic carbene complexes
The use of N-heterocyclic carbenes I–IV and related acyclic diaminocarbenes is a recentdevelopment in the synthesis of transition metal–carbene complexes (Figure 2)<2002AG(E)1290>. Experimental and theoretical studies have established that NHCs bind to thetransition metal by �-donation; back-donation from the metal is minimal, thus the electronicproperties of diheterosubstituted singlet carbenes are comparable to trialkylphosphines. Typicalprocedures for the synthesis of NHC–transition metal complexes are: (i) free carbene route (depro-tonation of the corresponding azolium salts with bases prior to metallation; (ii) direct metallation ofthe azolium salts with a basic metal precursor such as Pd(OAc)2 or [Ir(COD)(OEt)]2; (iii) reaction ofthe corresponding electron-rich alkenes (enetetramines) with mononuclear or bridged dinuclearorganometallic compounds; (iv) metal exchange starting from silver carbenes (transmetallation);and (v) oxidative addition of a low-valent metal to a 2-chloro-1,3-disubstituted imidazolinium salt.
BDur
TMS
TMS
PhLiB
TMS
Dur
BPh
Dur
TMS
B
TMSTMS B
Ph
DurDur
B Dur
Li+Li+
TMS
TMSB
B
Dur
PhDur
Li+–
–Li+Li
BDur
TMS
TMSB
TMS
TMSDur 2Li+
TMS
TMSB
BTMS
TMS
B
B
Ar
Ar
BTMS
TMSAr
TMS
TMSB
B
B
ArBut
ArAr
B
B
Ar
Ar
BTMS
TMS But
Ar
B
BB
But
Ar
Ar
TMSTMS
Ar Li+Li+ Li+
200a
–
–
203
198a
204205
ButLi–
1,2-Dur shift
0.5
Dur
–
Ar = Dur, Mes
– –
∆
∆
Scheme 50
I II III IV
N
NR
RN
NR
R
( )n N N
NR
RS
NR
Figure 2 N-Heterocyclic carbenes.
696 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
A new approach to the preparation of NHC–transition metal complexes was recently reportedby Cloke and co-workers <1999OM3228>. It concerns the possibility of obtaining group 10homoleptic carbene complexes via the co–condensation of nickel, palladium, or platinum vaporwith 1,3-di-t-butylimidazol-2-ylidene. This route provides a straightforward synthesis of thestable, two-coordinate metal–carbene complexes 206–208, one compound of which 207, hasbeen inaccessible to date by solution technique (Equation (29)).
+ M(at)Cocondense
–196 °C
206, M = Ni
207, M = Pd
208, M = Pt
2N
N
But
But
N
N
But
But
MN
N
But
But ð29Þ
Another interesting example of the formation of transition metal–carbene complex from freeNHC is the preparation of vanadium(V)–carbene adduct 209 in which the transition metal is in ahigh oxidation state (Equation (30)). In this case, complexation of an N-heterocyclic carbene tovanadium(V) results in an electrophilic singlet Ccarbene, which is typical of Fischer type systems,but is unusually supported by a high-oxidation-state metal center. Both solid samples anddichloromethane solutions of 209 are stable in air and showed no decomposition on standingfor over two months <2003JA1128>.
+ Cl3VO
209
Toluene, rt76%
N
N
Mes
Mes
N
N
Mes
Mes
V(O)Cl3 ð30Þ
Erker and co-workers used three different stable imidazole-derived carbene ligands to preparea series of trans-[(imidazolyl-2-ylidene)2MCl4 complexes of zirconium and hafnium<2002JOM(663)192>. Scheme 51 illustrates synthetic approaches to these species. Deprotonationof 1,3-diisopropylimidazolium chloride 210 with NaH–KOBut gave 1,3-diisopropylimidazol-2-yli-dene 213 in 95% yield. Treatment ofN-methylimidazole with 2-bromobutane yielded the imidazoliumsalt 211 which was converted to the stable carbene 214 by treatment with KH–KOBut. Finally, theimidazolium salt 212, prepared by N-alkylation of N-methylimidazole with bromomethyl-2,4,6-trimethylbenzene, was converted to the unsymmetrically substituted Arduengo carbene 215 by treat-ment with NaH in THF. Reaction of the carbenes 213–215 with MCl4(THF)2 (M=Zr, Hf) affordsthe corresponding carbene–group 4 Metal halide complexes 216–219 as stable solids.
The first carbene-linked cyclophane 221 was prepared by Youngs and co-workers from thebis(imidazolium) salt 220, which results from a straightforward alkylation reaction of 2,6-bis(imida-zolemethyl)pyridine. Silver oxide was used to deprotonate 220 and, at the same time, to introduce themetal center (Scheme 52) <2001OM1276>.
As a further development of the free carbene route the synthesis of N-borane-protected NHCcomplexes has been achieved as shown in Scheme 53. 1,10-Bis(3-borane-4,5-dimethylimidazo-lyl)methane 222 was deprotonated to give a dianionic dicarbene compound 223. Its reactionwith Cp2MCl2 (M=Ti, Zr) allowed the formation of the corresponding titanocene and zircono-cene complexes 224 and 225 in 75–80% yields <2002EJI1607>.
Metal acetates allow the synthesis of NHC complexes without isolation of free carbenes. Thisprocedure combines the advantages of readily available starting materials with the in situ depro-tonation of the azolium salts and avoids free carbenes or expensive organometallic precursors.For example, since the acidic methylene protons in bisimidazolium salts 226 are also attackedunder common deprotonation conditions, a pathway via free biscarbenes leads to a complexmixture of products. However, palladium(II) acetate in wet DMSO deprotonates 226 to givebridged palladium–biscarbene complexes 227 in 85–90% yields <1999JOM(572)239,2000CEJ1773>. The bisimidazolium salts 226 also undergo a selective deprotonation with sodiumacetate/platinum(II) halide, and this has been used in a one-pot synthesis of novel platinum(II)biscarbene complexes 228 (Scheme 54) <2002JOM(660)121, 2003JOM(671)183>.
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 697
Interestingly, the pK’s of the bisimidazolium salts 226 should make one think that NEt3 is notstrong enough to deprotonate the azolium center. Nevertheless the addition of an excess of thebase (20:1), together with the rapid coordination of the carbene to metal, displays the equilibriumof deprotonation to the formation of the desired products. Thus the synthesis of complexes 229and 230 includes the deprotonation of the bisimidazolium precursor with NEt3 in the presence of[RhCl(COD)2]. When the reaction is carried out in the presence of air, 229 is the major productobtained. Under inert conditions with degassed acetonitrile, complex 230 is mainly formed<2003IC2572>. A similar approach has been applied to the preparation of dirodium(I) bisimi-dazolium carbene complex 231 <2003OM440> and new ruthenium(II) CNC-pincer bis(carbene)-complexes 232 and 233 (Scheme 55) <2003OM1110>.
NaH/KOBut
THF, 95%
MCl4(THF)2
91–99%
210 213 216, M = Zr
217, M = Hf
+Cl–
N
N
N
NH
N
NMCl42
NaH/KOBut
THF, 65%
ZrCl4(THF)2
89%
211 214 218
+Br–
N
N
N
NH
N
NZrCl4
2
THF, 86%
ZrCl4(THF)2
94%
212 215 219
+Br–
N
N
N
NH
N
NZrCl4
2
NaH
Scheme 51
Ag2ON
N
N
Ag
NN
N
N
N
N
N
++ +
220
221
N
N
N
N
NH H
NBr Br N
N
N
N
N
NH H
i, ii
DMSO 55 °C
i. CH2Cl2, rt; ii. NH4PF6
2PF6–
2PF6–
2+
Ag
Scheme 52
698 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
231232
233
NN N
Rh
Bun
Br
N N
RhBr
Bun N NN
N NRuCOBr
Br
BunBun
N NN
N N
BunBun
C
Ru
C
NNC
C CN N =
2PF6–
2BH3.THF
THF, –78 °C
THF, –78 °CTHF, –78 °C
97%
2BuLi
222
223224, M = Ti (75%)
225, M = Zr (80%)
Cp2MCl2
2–
2Li+N
M
N
NNBH3H3B CpCp
N N
NNBH3H3B
N N
NNBH3H3B
N N
NN
Scheme 53
N
N CH2X2++ 2X–
227, M = Pd
228, M = Pt
Pd(OAc)2 or
PtX2, 2NaOAc
R = Me, Bun; X = Br, I
226
2 DMSO, rtN N
NNRR
N N
NNRR
MX XR
Scheme 54
[RhCl(COD)]2
+2I–
+ +
PF6–or
NEt3 + KI + KPF6
CH3CN
229230
N N N N
Rh RhII
N
Rh
N
NNII
MeCN NCMeN N
NN
+
Scheme 55
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 699
A further exploitation of the azolium route now covers metallocenes, such as 234. Thissynthesis is successful for both nickelocene and chromocene (Equation (31)) <1999OM529,2000JOM(596)3>.
Cl–+
+–C5H6
MN
N
MCl
Mes
Mes
N
N
Mes
Mes
234
M = Ni (70%), Cr (67%)
THF
ð31Þ
A recent paper has described an efficient entry into palladium complexes bearing NHC ligandson the basis of the oxidative addition Pd(PPh3)4 to the easily accessible 2-chloro-1,3-disubstitutedimidazolium salt 235 <2003OM907>. This novel method promises a broad substrate scope andallows for substantial structural variations since the required 2-chloro-1,3-disubstituted imidazo-lium salts can be easily prepared from cyclic ureas or thioureas on treatment with, for instance,oxalyl chloride. Examples are depicted in Schemes 56 and 57. Interaction of the imidazoliumsalts 235 (X=PF6, BF4) with an equimolar amount of Pd(PPh3)4 in refluxing dichloromethaneleads to the formation of cis-236 as the primary products, which isomerize with time to the morestable trans-236. Although the reactivity of chloride 235 (X=Cl) follows the same trend, givingrise to the expected cationic complex trans-236 in 87% yield, the equilibrium between the cationicand the neutral Pd–NHC complexes leads to small amounts of complex 237 in addition to 236.This propensity is more pronounced in case of the enantiomerically pure NHC complex 239,which is obtained as the only product on treatment of the chiral imidazolium salt 238 withPd(PPh3)4 under similar conditions.
Complexes of NHC can also be generated starting from aminals. In particular, the successivetreatment of [PdCl2(PEt3)2] with the aminal 240 leads to the formation of trans-mono- and trans-bis(carbene) complexes 241 and 242 containing the 1,3-diallylimidazolidin-2-ylidene ligand. If, inaddition, [Pd2Cl4(PEt3)2] is employed, the cis-complexes 243 and 244 are obtained in high yieldsas the only organometallic products (Scheme 58) <2002OM5428>.
Special NHC-transfer reagents are the silver(I) complexes <2002HAC534>. They are formed ina simple way by treatment of imidazolium salts with Ag2O and transfer their NHC ligands toother metals, for example, Pd, Pt, or Rh <2002JCS(D)2852, 2002TA1969, 2003JCS(D)699>. Thistechnique overcomes the difficulties arising from the use of strong base to yield free heterocycliccarbenes and seems to be particularly effective in the case of functionalized NHCs. For example,Matsumoto and co-workers have demonstrated that the imidazolium chloride 245 reacts with an
N
NCl
+X–
+X–
X–+
Ph3P +
235cis-236
trans-236237
X = PF6, BF4, Cl
X = Cl
Pd(PPh3)4
–2PPh3
N
NPd PPh3
PPh3
Cl
N
NPd ClPPh3
PPh3N
NPd ClPPh3
Cl
Scheme 56
700 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
Ag2O suspension in dichloromethane at a ratio of 1:1 to afford 246. Attempt to prepare the freecarbene by deprotonation of the imidazolium salt 245 with either KOBut or KH was notsuccessful probably due to the high acidity of the methylene protons linking phenyl and imidazolerings (Scheme 59) <2002JOM(654)233>. The silver-NHC complex 247 was prepared in a similarmanner. It smoothly reacts with [PdCl2(COD)] to yield the corresponding palladium–carbenecomplex 248 <2002OM5204>.
Cl–+
Cl2C=S
82%
238239
Pd(PPh3)4
–3PPh3
85%
64%
N N
Cl
N N
S
N N
PdCl
ClPh3P
NH HN
[C(O)Cl]2
Scheme 57
[PdCl2(PEt3)]2
PdCl2(PEt3)2
–PEt3, –Me2NH
240 trans-241 trans-242
cis-243 cis-244
R = CH2=CH-CH2
240
N
NR
RH
NMe2
N
NR
R
Pd PPh3
Cl
Cl N
NR
R
PdN
NR
R
Cl
Cl
N
NR
R
Pd ClPPh3
Cl N
N
R
Pd ClCl
NRNR
–PEt3, –Me2NH
240
–PEt3, –Me2NH
–Me2NH
R
Scheme 58
NN Me
ClCl
2Cl–
Ag2O
+ + +
CH2Cl2, rt
95%
60 °C, 2 h
91%245
246
2
N NNN
AgAg
MeMe
ClCl
N NNN MeMe
Scheme 59
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 701
247 248
N N
AgBr
O
NN N
NPd
O
ClCl
An entirely different approach for the generation of the metal–NHC complexes is based on thetemplate-controlled formation of NH,O- and NH,NH-stabilized cyclic carbene ligands<1999CCR(182)175>. An example is outlined in Scheme 60. The 2,3-dihydro-1H-benzimidazol-2-ylidene complexes 252 (M=Cr, W) have been produced by template-controlled generation of acarbene ligand from 2-azidophenyl isocyanide and [M(CO)5(THF)]. The polar Ph3P¼N function incomplexes 249 can be hydrolyzed with H2O/HBr to afford the unstable 2-aminophenyl isocyanidespecies 250, which spontaneously cyclize by intramolecular nucleophilic attack of the primary amineat the isocyanide carbon to yield the complexes 251. Double deprotonation of the cyclic NH,NH-carbene ligand in 251 with KOBut and reaction with 2 equiv. of allyl bromide affords the N,N0-dialkylated benzannulated N-heterocyclic carbene complexes 252 <2003CEJ704>.
6.22.3.1.2 Silicon-substituted carbene complexes, R3Si(X)C¼MLn
The silyl(ethoxy)carbene complexes XPh2Si(EtO)C¼W(CO)5 253 and 256 were prepared by theFischer route starting from W(CO)6 and LiSiPh2X followed by alkylation of the formed anionicacyl complex with [Et3O]BF4. For the synthesis of 256, an excess of [Et3O]BF4 has to be avoided,because otherwise the amino group is cleaved. Reaction of 253 with Me2NH and of 256 withMeNH2 resulted in the formation of the corresponding silyl(amino)carbene complexes 254 and257 in high yields. When ether solutions of 254 or 257 were irradiated with UV light, CO was
NC
N3 NC
N3
MOC COOC CO
CO
NC
N
MOC COOC CO
CO
PPh3
NC
NH2
MOC COOC CO
CO
N NH H
M
CO
COOCCOOC
N N
MCO
COOCCOOC
M(CO)5(THF)
THF, rt63–65%
PPh3
THF, rt75–80%
HBr/H2O
78–85%
i. KOBut
ii. C3H5Br
65%
249
250251252
M = Cr, W
Scheme 60
702 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
evolved, and the thermally stable tetracarbonyl complexes 255 and 258 were obtained (Scheme 61).The spectroscopic data clearly showed that the olefinic group in 255 and the amino group in 258 arecoordinated to the metal center <2000EJI1811>.
Upon photolysis of the carbene complexes R12RSi(R2N)C¼M(CO)5 (M=Cr, Mo, W;
R12RSi¼Mes2HSi or Ph3Si) the stable 16-electron carbene complexes R1
2RSi(R2N)C¼M(CO)4are obtained. These species are stabilized by intramolecular interaction of one of the siliconsubstituents with the metal atom. Thus in Mes2SiH(Me2N)C¼W(CO)4 the Si–H group interactswith the tungsten atom. In the Ph3Si derivative, the W–Cphenyl distances indicate that the ipsocarbon atom is mainly involved in the interaction with the metal atom. Despite the agosticinteraction in the silylcarbene complexes, the coordination site is still accessible. Thus, the reactionof R1
2RSi(R2N)C¼M(CO)4 with CO, phosphines, phosphites, or isonitriles quantitativelyyielded 18-electron carbene complexes cis-R1
2RSi(Me2N)C¼W(CO)4L (L=CO, RNC, R3P,(RO)3P) <1994OM1554, 1994ICA(220)73>.
Formation of the silyl-substituted alkylidene tantalum and tungsten complexes from reactionsof alkylidene complexes with silanes have been reviewed <2002JMOC(190)101>. Scheme 62illustrates this synthetic methodology. Addition of the silanes H2SiRPh to the alkylidene com-plex 259 leads quantitatively to the disilyl-substituted alkylidene complexes 260. The reactionoccurred exclusively with the alkylidene (¼CH–TMS) ligand, and the resulting complexes werefound to be unreactive toward excess silane. More interestingly, addition of H2SiRPh to 261 ledto the evolution of H2 and the formation of 1,10-metalla-3-silacyclobutadiene complexes 262.The reaction of 261 with disilylmethane (H2PhSi)2CH2 also generates H2 and a metalladisila-cyclohexadiene 263 <2001OM1504>. Novel products, unavailable by other routes, can thus beprepared.
W(CO)6
Me2NH
i. LiSiPh2(CMe=CHMe)
ii. [Et3O]BF4
i. LiSiPh2NEt2ii. [Et3O]BF4
Et2O, rt 71%
59%
hν
Et2O, –20 °C
Et2O, –20 °C
93% 255
253 254
Ph2Si
Me2NW(CO)5
Ph2Si
EtOW(CO)5
Ph2Si
Me2NW(CO)5
W(CO)6
MeNH2
Et2O, rt
95%60%
hν
62%
258
256 257
Ph2SiNEt2
NW(CO)5
Ph2SiNEt2
EtOW(CO)5
Ph2SiNEt2
NW(CO)5
HMe
HMe
Scheme 61
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 703
6.22.3.2 Functions with a Formal Tin–Carbon and Lead–Carbon Double Bond
The synthesis and properties of low-coordinated compounds of tin and lead are collected in therecent review by Weidenbruch <2001MI621>. Stannaethene (TMS)2C¼SnMe2 is formed as ashort-lived intermediate by reaction of (TMS)2BrC–Sn(Y)Me2 with LiR via (TMS)2LiC–Sn(Y)Me2 (Y=F, Br, PhO; R=organyl) and its existence was demonstrated by characteristictrapping experiments including the formation of thermolabile adduct with anthracene, which wasused as a ‘‘store’’ for this compound <1998CEJ2571, B-1998MI106, 2000JOM(598)292,2000JOM(598)304, 2000CJC1412>. Isolable compounds with a C¼Sn double bond are stillextremely rare <1998CCR565>. The first members of this series with stability at room tempera-ture were 264 and 265 prepared by Berndt and co-workers, both by the reaction betweenstannylenes and the cryptocarbene [(TMS)2C(BBu
t)2C] <1987AG(E)546>. More recently thepreparation of stannaethenes 266 <1997JOM(530)255> and 267 <1999HAC554> has beendescribed. The X-ray structure analysis of 266 reveals a strictly planar environment of thetricoordinated tin and carbon atoms and a slight twisting of the C¼Sn bond<1997JOM(530)255>.
B
BSn
But
But
TMSTMS
TMSTMS
B
BSn
But
But
N
NSiMe2
But
But
B
BSn
But
But
264 265 266, R1 = R2
= 2-But-4,5,6-Me3C6H
267, R1 = 2-But-4,5,6-Me3C6H,
R2 = (TMS)3Si
TMS
TMS
TMS
TMS TMS
TMS R2
R1
H2SiRPh
–H2, –PMe3
Hexane, rt
259 260
H2SiRPh
PhH2Si SiH2Ph
262
263
–2H2
Pentane, rt10%
261
R = Me, Ph
PMe3
TaTMSTMS
TMSTMS
TaRPhHSi
TMSTMS
TMS
TMS
PMe3
TaPMe3
TMS
TMS TMS
Ta
TMS
TMS
Ph
R
PMe3PMe3
TMS
Si Ta
TMS
Si
TMSH
Ph
PMe3
PMe3TMS
H
Ph
–2H2
Pentane, rt44–78%
Scheme 62
704 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
Other known compounds with tricoordinated carbon and tin atoms can better be described asLewis base–acid adducts on account of their geometries and large C–Sn bond lengths. Examplesof such compounds are zwitterionic adducts 268–270 prepared from the reaction of a nucleophiliccarbene with tin(II) chloride <1995CB245>, a diarylstannylene <1995CC1157>, or diarylplum-bylene <1999CC1131>. The related species 271 and 272 were also obtained directly from a stablecarbene and the corresponding stannylene and plumbylene. Each of the crystalline adducts is amonomer, having an exceptionally long central bond between the three-coordinated carbon andthe M atoms.
+ + –
268, M = Sn, R = Cl <1995CB245>
269, M = Sn, R = 2,4,6- Pr3C6H2 <1995CC1157>
270, M = Pb, R = 2,4,6- Pr3C6H2 <1999CC1131>
i
i
271, M = Sn, R = ButCH2
272, M = Pb, R = ButCH2
Pri
Pri
MR
R–
N
NR
R
MN
NR
R
As mentioned in the previous section, reaction of an enetetramine with a coordinativelyunsaturated metal complex is a standard method for the preparation of complexes withN-heterocyclic carbene ligands. Hahn and co-workers applied this strategy to the synthesis ofa zwitterionic carbene–stannylene adduct via cleavage of a dibenzotetraazafulvalene by astannylene. Thus reaction of the stannylene 273 with the tetramethyldibenzotetraazafulvalene274 leads via C¼C bond cleavage in 274 to the carbene–stannylene adduct 275<2001JOM(617/618)629> (Scheme 63).
The molecular structure of 275 is similar to those of the carbene–silylene adduct reportedby Lappert <1999CC755> or the carbene plumbylene adduct described by Weidenbruch<1995CC1157>. None of these species exhibits properties consistent with a C¼M double bond.
Sn[N(TMS)2]2
N
NSn
N
N
NH
NH
N
N
N
N
N
N
NSn
N
N
N
N
N
+–
Toluene, rt, 24 h
67%
THF, 36 h,
83%
273
274
275
Scheme 63
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 705
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Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 709
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710 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal
Biographical sketch
Vadim D. Romanenko was born in Lugansk,Ukraine, in 1946. He studied at the Instituteof Chemical Technology (Dnepropetrovsk)and received his Ph.D. degree there underthe direction of professor S. I. Burmistrov.Since 1975 he has been working at theNational Academy of Sciences of Ukrainefrom which he earned his Doctor of Chemis-try degree in 1988. He became a full professorin 1991. He has been a visiting scientist at theCentre of Molecular and MacromolecularStudies in Lodz (Poland), the ShanghaiInstitute of Organic Chemistry (China), theUniversity of Pau & des Pays de l’Adour(France), the University Paul Sabatier(France), the University California Riverside(USA). His research interests include a widerange of topics at the border between organicand inorganic chemistry, in particular thechemistry of multiply bonded heavy maingroup elements. He is the author of approxi-mately 260 papers on organoelement chemis-try. He is also author of numerous reviewsand two monographs on low-co-ordinatedphosphorus compounds.
Valentyn Rudzevich was born in Kazatin,Ukraine, in 1968. He received his Diplomadegree in 1992 from Taras Shevchenko KievState University. Since 1992 he has beenworking at the Institute of Organic Chemistryof National Academy of Science of Ukraine,from which he received his Ph.D. degreeunder the supervision of professorV. D. Romanenko in 1997. Afterwards, hecarried out postdoctoral studies at UniversitePaul Sabatier (Toulouse, France), Universityof California Riverside (USA) and JohannesGutenberg Universitat Mainz (Germany). Onhis return to Kiev, he joined the Institute ofOrganic Chemistry where he is presently ascientist researcher. His research interests arefocused on organoelement compounds, short-lived intermediates, and co-ordination chem-istry.
# 2005, Elsevier Ltd. All Rights ReservedNo part of this publication may be reproduced, stored in any retrieval systemor transmitted in any form or by anymeans electronic, electrostatic, magnetictape, mechanical, photocopying, recording or otherwise, without permissionin writing from the publishers
Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 661–711
Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 711
6.23
Tricoordinated Stabilized Cations,
Anions, and Radicals, +CX1X2X3,�CX1X2X3, and _CX1X2X3
M. BALASUBRAMANIAN
Pfizer Global Research and Development, Ann Arbor, MI, USA
6.23.1 CARBON-CENTERED CATIONS BEARING THREE HETEROATOM FUNCTIONS 7146.23.1.1 Introduction 7146.23.1.2 Cations Bearing Three Halogens 7146.23.1.3 Cations Bearing Halogen and Chalcogen Functions 7146.23.1.4 Cations Bearing Halogen, Other Elements, and (Possibly) Chalcogen Functions 7146.23.1.4.1 Cations bearing two halogen and one nitrogen functions 7146.23.1.4.2 Cations bearing two halogen and one other heteroatom functions 7146.23.1.4.3 Cations bearing one halogen, one chalcogen, and one nitrogen functions 7146.23.1.4.4 Cations bearing one halogen and two nitrogen functions 715
6.23.1.5 Cations Bearing Three Chalcogen Functions 7166.23.1.5.1 Three oxygen functions 7166.23.1.5.2 Three sulfur functions 7166.23.1.5.3 Three selenium functions 717
6.23.1.6 Cations Bearing Chalcogen and Nitrogen Functions 7176.23.1.6.1 Two oxygen and one nitrogen functions 7176.23.1.6.2 Two sulfur and one nitrogen functions 7176.23.1.6.3 Two selenium and one nitrogen functions 7186.23.1.6.4 Two different chalcogen and one nitrogen functions 7186.23.1.6.5 One oxygen and two nitrogen functions 7186.23.1.6.6 One sulfur and two nitrogen functions 7196.23.1.6.7 One selenium and two nitrogen functions 719
6.23.1.7 Cations Bearing Chalcogen, Metal, and (Possibly) Nitrogen Functions 7196.23.1.8 Cations Bearing Three Nitrogen Functions 7206.23.1.9 Cations Bearing Nitrogen and Other Element Functions 7216.23.1.10 Cations Bearing Phosphorus and Silicon Functions 722
6.23.2 CARBON-CENTERED CARBANIONS BEARING THREE HETEROATOM FUNCTIONS 7226.23.2.1 Carbanion Bearing Three Halogens 7236.23.2.2 Carbanions Bearing One Halogen and Two Sulfur Functions 7236.23.2.3 Carbanions Bearing One Halogen and Two Phosphorus Functions 7236.23.2.4 Carbanions Bearing Three Nitrogen Functions 7236.23.2.5 Carbanions Bearing Three Sulfur Functions 7236.23.2.6 Carbanions Bearing Three Phosphorus Functions 7236.23.2.7 Carbanions Bearing One Phosphorus and Two Sulfur Functions 7246.23.2.8 Carbanions Bearing One Nitrogen and Two Sulfur Functions 724
6.23.3 CARBON-CENTERED RADICALS BEARING THREE HETEROATOM FUNCTIONS 724
713
6.23.1 CARBON-CENTERED CATIONS BEARING THREE HETEROATOM FUNCTIONS
6.23.1.1 Introduction
Carbocations with three heteroatom substitutents attached to carbon are popular reaction inter-mediates. They are stabilized by electron donation from lone pairs of electrons from heteroatomsinto the vacant �-orbitals on carbon. Nitrogen is the most effective of the three commonheteroatoms (O, N, S) with respect to electron pair donation. The presence of just one nitrogenfunction can enable the salt of a formal carbocation to be more stable and isolable. With onenitrogen atom attachment, there are two resonance hybrid structures possible, carbenium ion 1(+ve charge on carbon) and iminium ion 2 (+ve charge at nitrogen). Such compounds aregenerally considered to have the charge on nitrogen. Such positively charged derivatives ofcompounds are considered in Chapter 6.20. When the carbocation has more than one heteroatomfunction attachment then there are further possibilities for charge delocalization.
6.23.1.2 Cations Bearing Three Halogens
Trihalomethyl cations CX3 (X=Br, Cl, F) have been generated at low temperature from tetra-halomethanes on reaction with antimony pentahalides, and they have been reviewed earlier<1995COFGT(6)725>. Bromochlorofluoromethylium ion has been generated from bromochloro-difluoromethane <1997JPC(A)8489>. The �-electron donor ability of fluorine is more than offsetby its electron withdrawing inductive effect, thus the trifluoromethyl cation is less stable than theother trihalomethyl cations.
6.23.1.3 Cations Bearing Halogen and Chalcogen Functions
Fluoroformic acid is an intermediate in the oxidation of fluorocarbons and ozonolysis of fluoroalkenes.Its potential role in the depletion of the ozone layer in the stratosphere was explored in the early 1990s.Neutral fluoroformic acid does not exist because of its autocatalytic decomposition to HF and CO2.However, its conjugate acid and base protonated fluoroformic acid [FC(OH)+2 ] and fluoroformate ion[FCO�2 ], respectively, are expected to be more stable due to its resonance stabilization. Protolyticionization of t-butyl fluoroformate with fivefold excess of FSO3H/SbF5 in SO2ClF resulted in a deepyellow solution containing the carbocation +CF(OH)2 <1997AG(E)1875>. Bromotrifluoromethane,further reacted with H3O
+ to produce the carbocation +CF2OH <1997JPC(A)8489>.
6.23.1.4 Cations Bearing Halogen, Other Elements, and (Possibly) Chalcogen Functions
6.23.1.4.1 Cations bearing two halogen and one nitrogen functions
The preparative methods for dihaloiminium salts such as N,N-dimethyldihaloiminium halides 3(X=Cl, Br, I) and pyrrolidinedichloroiminium chloride 4 have been reviewed previously<1995COFGT(6)725>. These salts are important reagents and have a wide variety of syntheticapplications. No further development has been found on these types of salts.
6.23.1.4.2 Cations bearing two halogen and one other heteroatom functions
Several transition metal complexes exist in which CX2 acts as a ligand. Such metal complexeshave overall positive charge and have been reviewed <1995COFGT(6)725>. No further devel-opment has been seen for these types of transition metal complexes since 1995.
6.23.1.4.3 Cations bearing one halogen, one chalcogen, and one nitrogen functions
The chlorination of N-methylbenzothiazole-2-selone 5 and 1,1-dimethylselenourea 7 with SO2Cl2 andchlorine produced corresponding benzothiazolium 6 and uronium 8 salts, respectively, and X-ray studieshave been conducted for these salts <1999JCS(D)4245>.
714 Tricoordinated Stabilized Cations, Anions, and Radicals
N
SCl
Me
+SO2Cl–
X
YNR2
X
YN
X
XN
X
XNR+
R
+ R
RX–+ + X–
N
SSe
Me
N
H2NSe
MeMe N
H2N
MeMe
Cl SeCl5
1 2 3 X = Cl, Br, F 4
5 6 7 8
+–
6.23.1.4.4 Cations bearing one halogen and two nitrogen functions
Tetramethylfluoroformamidinium hexafluorophosphate (TFFH) 9 a nonhygroscopic salt, stableunder ambient conditions, was obtained from 10 with excess of anhydrous KF <1995JA5401>.The salt 10 was prepared previously from tetramethylurea using phosgene. A new improvedsynthetic procedure for 10 from tetramethylurea using oxalyl chloride has been reported<1989TL1927>. TFFH appears to be an ideal coupling reagent for solid-phase syntheses, beingreadily available, inexpensive and capable of providing peptides of high quality <2000OL3539>.A new and convenient method for the solid-phase preparation of pentasubstituted guanidinesinvolves the use of aminium/uranium salt-based reagents. These compounds have been usedmainly as coupling agents in peptide synthesis and they activate the carboxyl group of theamino acids <2000OL3539>.
Bispyrrolidinefluoromethylium tetrafluoroborate 11 is a convenient reagent for the solid-phasesynthesis of a range of peptides incorporating sensitive amino acids and 11 has been prepared from1,10-carbonylbispyrrolidine 13a using oxalyl chloride <1998CL671>.
Bispiperidinechloromethylium tetrafluoroborate 12 was prepared from 1,10-carbonylbispi-peridine 13b via deoxygenation using phosgene <2000OL3539>. Pyrrolidine-1-carboxylic aciddialkylamides 14 and 15 reacted with COCl2 to form N,N-dialkyl-N-pyrrolidinochloromethyl-carbenium salts 16 and 17 <2000OL3539>.
2-chloro-1,3-dimethylimidazolinium chloride 19 has been prepared from 1,3-dimethylimidazo-lidine-2-one 18 and oxalyl chloride <1986T6645>. 2-Chloro-1,3-dimethylimidazolinium chlorideis a powerful dehydrating agent and 19 is equivalent to dicyclohexylcarbodiimide (DCC). Theadvantages of 19 are low cost, nontoxic, and easy removal of product from the reaction mixtureby simple washing with water. Chiral guanidines prepared from 19 can be considered as superbases due to their strong basic character <2000JOC7770>. The synthetic utility of 19 has beenwell demonstrated as an effective dehydrating agent in the following synthetic reactions: esteri-fication of hindered alcohol, acylation of 1,3-diones (cyclic), dehydration of oximes to nitriles(aromatic), and dehydration of benzamide to nitriles <1999JOC6984>. Isocyanides, isothiocya-nates, and carbodiimides were synthesized from formamides, dithiocarbamates, and thiourea,respectively <1999JOC6984>. 2-Chloro-1,3-dimethylimidazolinium chloride is used as a couplingagent for the conversion of trimesitylchlorosilane to hexamesityldisilane <1984JOMC(264)179>.Further reactions of 19 are explored with L-valinol, benzamide, and methyl(S)-1-phenylethyl-amine to produce more useful and novel compounds <2000JOC7770>.
N
O
N
(CH2)n
N
O
NR
R N NR
Cl
R+
NN
Me
MeCl
+N
N
O
Me
Me
Cl– or BF–4
or BF–4Cl–
MeN
MeX
NMe
Me+
n(H2C)
N N
(CH2)nn(H2C)
X
+
13a n = 1; 13b n = 2
18 19
PF–6
PF–6
or BF–4
11 n = 1, X = F 12 n = 2, X = Cl9 X = F, 10 X = Cl
14 R = Me, 15 R = Et 16 R = Me, 17 R = Et
Tricoordinated Stabilized Cations, Anions, and Radicals 715
6.23.1.5 Cations Bearing Three Chalcogen Functions
6.23.1.5.1 Three oxygen functions
Several examples of tris(alkoxy)methylium salts were reviewed earlier and no furtheradvances have occurred in this area since 1995 <1995COFGT(6)725>. Trimethylsilylacetylene20 has been deprotonated with BuLi and subsequently reacted with 21 to give 1,1,1-triethoxy-2-trimethylsilylpropyne 22, thus exploring the synthetic utility of triethoxycarbenium tetrafluoro-borate 21 <1997TL6803>. Protonation of dimethyl carbonate by the super acids system HF,MF5 (M=As, Sb) afforded dimethoxyhydroxycarbenium hexafluorometallates 23, which arecolorless, moisture sensitive salts. These salts are soluble in SO2, and are stable at �70 �C forseveral weeks <2000EJI1261>.
6.23.1.5.2 Three sulfur functions
Stable salts of carbenium ions bearing three sulfur functions have been reported. The methodsfor their preparation are analogous to those used for the tris(alkoxy)carbenium ions but, sinceit is much easier to alkylate sulfur than oxygen, a wider range of alkylating agents can beused.
Substituted 1,3-dithiolane- and 1,3-dithioles-2-thiones 24 and 26 were also alkylated usingvarious methylating agents to provide corresponding salts 25 and 27. Thiones are often alkylatedwith the most commonly used methylating agents such as alkyl halides and methyltrifluoro-methane sulfonate <1997TL81, 1991S26, 2000CL842, 1998CC361, 1998JMAC1185,1999JCS(P2)505>, although dimethyl sulfate has been used occasionally <1991S26>.
4,5-Disubstituted 1,3-dithiole-2-thiones 26a and 26b were methylated using methyltrifluoro-methane sulfonate to provide corresponding salts 27a and 27b in quantitative yield. Derivatives of1,3-dethiole-2-thiones 28, 29 were methylated to the corresponding 1,3-dithiolium iodides 30, 31,and 31 underwent desulfurization with subsequent self-coupling to afford the dimeric product 32<1991S26, 1995JPR299>.
HO O
OMe
Me
MF–6MeSi
Me
Me
Me SiMe
Me
OEt
OEtOEt
S
SS
R1
R2
S
SS
RR
RR
S
SS
RR
RR
Me S
RR
RR
S
S RS
RR
R
S
SS
Me
R1
R2
S
SS
R1
R2
S
SS
Me
R1
R2
CF3SO–3 I– or CF3SO–
3
I–
+
+
+
28 R = H 29 R = SMe
26a, 27a R1R2 = (S–CH2CH2–S)
26b, 27b R1 = R2
= CH2–S–(C=O)Me
+
20 22 23
24 25 26 27
24a, 25a R1 = R2 = H
24b, 25b R1 = R2 = Me
M = As, Sb
32 R = SMe30 R = H 31 R = SMe
OEt
EtOOEt
BF–4
21
+
716 Tricoordinated Stabilized Cations, Anions, and Radicals
Several coupling products of substituted thienodithiolylidenefluorene 35 were prepared fromsubstituted fluorene and thienodithiolane carbenium ion 34, which in turn was derived fromthienodithiole-2-thione 33 <1999JCS(P2)505>. The degree of intramolecular charge transfer(ICT) in dithiolylidene fluorenes bearing fused thiophene has been investigated by UV-VISspectroscopy <1999JCS(P2)505>. Tris(trifluoromethyl(chalcogenato)carbenium ions 36 and 37were prepared from fluoro tris(trifluoromethylthio)methane and fluoro tris(trifluoromethylse-leno)methane <1996CB1383>. Tris(chalcogenato)carbenium ion 38 was generated from CBr4and ArSCu <1996AG(E)300>. Further reaction of tris(trifluoromethylthio)carbenium hexa-fluoroarsenate 36 with benzene and anisole produced benzophenone and 4,40-dimethoxyben-zophenone, which are products of hydrolysis of the diphenylmethane intermediate<1995CB435>.
6.23.1.5.3 Three selenium functions
Tris(trifluoromethylseleno)carbenium hexafluoroarsenate 37 was prepared from tetrakistrifluoro-methylselenylmethane <1996CB1383> and is stable at �20 �C. Trisisoopropylbenzene selenidereacted with tetrabromomethane to form tris(triisopropylbenzene)selenide 39 <1996AG(E)300>.
MeMe
MeMe
Me
Me
SS
SS
S
SS
Me
CF3SO–3
SS
SS +
Ar = *33 34 35
F3CX XCF3
XCF3
+
36 X = S, AsF– 6
37 X = Se, PF– 6
38 X = S, AsF– 6
39 X = Se, PF– 6
ArX
X XArAr
+
6.23.1.6 Cations Bearing Chalcogen and Nitrogen Functions
6.23.1.6.1 Two oxygen and one nitrogen functions
Mono-O-protonated carbamic acids andN-methyl carbamate were prepared using super acids (FSO3H/SO2ClF and FSO3H:SbF5/SO2ClF) at�78 �C, and these salts were characterized by 1H, 13C, 15NNMRspectroscopy <1998JOC7993>. A stable salt of 1,9-diethoxy-1-methoxy-3,5,7,9-tetraphenyl-2,4,6,8-tetraazanonatetraenylium hexachloroantimonate 41 was prepared from the corresponding ester 40, byregioselective O-alkylation with triethyloxonium hexachloroantimonate <1996MI371>. Further reac-tion of dimethylaminodiethoxycarbenium tetrafluoroborate 42 with N,N-dimethylamine producedbis(dimethylamino)diethoxymethane <2000JPR256>.
6.23.1.6.2 Two sulfur and one nitrogen functions
Methylations of few cyclic dithiocarbamates with dimethyl sulfate yielded corresponding thio-carbamate salts and have been reviewed previously <1995COFGT(6)725>. Dithiocarbamatesalts 45 and 46 are most often prepared by S-alkylation of dithiocarbamates 43 and 44<1995JOC2330>.
Tricoordinated Stabilized Cations, Anions, and Radicals 717
6.23.1.6.3 Two selenium and one nitrogen functions
Reaction of 2-chloro-1,3-diselenoazolium tetrafluoroborate 47 with morpholine to form 1,3-diselenazole-2-morpholinium salt 48 has been reported <1987PS187>.
6.23.1.6.4 Two different chalcogen and one nitrogen functions
Alkylation of 3-methyl-5-phenyl-3H-1,3,4-oxadiazole-2-thione 49 with MeI produced salt 50<1995JOC2330>. Alkylation of diethylthiocarbamic acid O-p-tolyl ester 51 with triethyloxoniumtetrafluoroborate produced a moisture sensitive, colorless solid stable salt 52 <2001EJO83>.
6.23.1.6.5 One oxygen and two nitrogen functions
Alkylation of substituted ureas with 21 primarily produced O-alkylated stable and isolableuronium salts. This work has already been reviewed <1995COFGT(6)725>. It is interesting tonote that in some cases, N-alkylation of tetraalkylurea competes with O-alkylation. Thus analternative synthetic strategy is employed for the preparation of uronium salts starting fromN,N,N0,N0-tetramethylchloroformadinium chloride whereby N-alkylation can be avoided.
N,N,N0,N0-Tetramethyl(succinimido)uronium tetrafluoroborate 54 and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate 56 have been used as coupling agents insolid-phase peptide synthesis. They are excellent activating agents and reduce racemization duringcondensation of peptide segments. They are useful tools for the formation of active esters suitablefor coupling in mixed aqueous or organic media.
SbCl–6
O NN
S Me
Me
Me
O
SN
Me
Me
I–
NS Me
S
Me
NS Me
S
Me
R MeI–
SeN
Se
R
Me
O
SN
Me
Me
O NN
S Me
Se
Se
ClBF–
4
BF–4
BF–4
BF4–
NO NN NO O
R
R O
O
Et
Et
Me2N OEt
OEt
NOH
OO N
O
O
O
NN
Me
Me
Me Me
NN
N
O–K+
O
NMe
Me
NN
N
NMe
Me
+
+
+
+
PF–6
+
+
+
BF–4
+
+R =
43 R = H, 44 R = Me 45 R = H, 46 R = Me
40
47 48
49 50 51 52
53 54 55 56
41
42
O
718 Tricoordinated Stabilized Cations, Anions, and Radicals
N-Hydroxysuccinimide 53 reacted with 10 to form N,N,N0,N0-tetramethyl(succinimido)uroniumtetrafluoroborate 54 <1989TL1927>. Several esterification reactions have been reported in whichN,N,N0,N0-tetramethyl(succinimido)uronium tetrafluoroborate 54 is used as a coupling agent. Thesalt shown in 54 has been used as a feed stock to produce several other useful coupling agents<1997JA640, 1999HCA1311, 1999BMCL2229, 1999JA5860, 2000S707, 2000BMC2359,2002OL1075>.
2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate 56 was preparedfrom benzotriazole-N-oxide 55 using 10 <1989TL1927, 1984S572, 2002AG(E)442> and the saltgiven in 56 is used as a coupling agent for several esterification reactions <1999T1129,2000BMCL13, 2000AG(E)1626>.
6.23.1.6.6 One sulfur and two nitrogen functions
There has been considerable interest in the usage of isothiuronium salts in membranology and inorganic synthesis. These salts are used to regulate free radical oxidation in biological membranes.Functional transformation of CH2X to CH2SH via isothiuronium salt has been shown to have agreat deal of synthetic utility in organic synthesis.
S-Alkylation of tetramethylthiourea 57, with MeI gave isothiuronium salt 58 <1995JOC2330>.Salt of disulfide 59 was obtained from 57 via oxidation with bromine <1997JCS(D)1857>.2-Bromo-2H-1,4-benzoxazin-3(4H)-one 60 and 2-bromo-2H-1,4-benzothiazin-3(4H)-one 61 wereconverted into corresponding isothiuronium salts 62 and 63 by reaction with thiourea in acetone<1996JHC1623>. Further, these salts were converted to the corresponding mercapto derivativesby alkaline hydrolysis. Isothiuronium salt 65 was obtained from 3-chloro-2-chloromethylpropene64 and thiourea via S-alkylation <1996AJC1261>. The S-alkylation of thiophosphate 66 bythiourea, followed by ring opening, produced thiuronium salt 67 <1996RJGC1072>. Bicyclicthiophosphate 68 reacted with thiourea to provide a high yield of betaine 69, which is of certainbioregulating interest as a radioprotector, and the overall reaction is a thione-thiol isomerization(ring-opening products) <1996RJGC1362>. Disodium[(3-methylthioureido)methylene]bispho-sphonate 70 is easily alkylated in aqueous solution with MeI to give stable and isolable thiur-onium salt 71 <1996RJGC1442>. 4-Nitrophenylisothiuronium salt was obtained from4-nitrobenzenethiol and NH2CN <1997JCS(P2)1555>. 6,60-Bischloromethyl-[2,20]bipyrazinyl iso-thiuronium salt 72 was obtained from 6,60-bischloromethyl-[2,20]bipyrazine and thiourea<1999EJO1427>. Tetramethyluronium and -thiouronium salts 75 and 76 were preparedfrom N-hydroxy-2-oxopyridine 73 and N-hydroxy-2-mercaptopyridine 74, respectively<1999JOC8936>. Novel carbanion ionophores based on thiuronium derivative 78 have beenprepared via S-alkylation of N-benzyl-N-butylthiourea 77 using MeI, and their application to ionselective electrodes has been examined <2001CL382>.
6.23.1.6.7 One selenium and two nitrogen functions
Synthesis of dipyridoimidazolone 80 from 6H-dipyridoimidazole-6-selone 79, was accomplished viaSe-alkylation of 79 with MeI followed by hydrolysis of the resulting salt, 6-(methylselan)dihydro-imidazolium iodide 81, produced 80 <2000EJI1935>.
6.23.1.7 Cations Bearing Chalcogen, Metal, and (Possibly) Nitrogen Functions
General methods for the preparation of cationic carbene complexes of mercury and platinumcomplex have been reviewed <1995COFGT(6)725>. Lewis acid adducts of stable nucleophiliccarbene 82 with various metals have been reported <1995AG(E)487>.
Tricoordinated Stabilized Cations, Anions, and Radicals 719
N
X S NH2
NH2O
H
OP
OS
O
OO
OP
O–S
O
OS
H2N NH2
O
OP O
O
O
OO
S
O
O
O
OP
O
SH2N
H2N
SO–
N
S
N
P
PMe
HH O
ONaOH
ONaO OH
N
N N
N
S
NH2
H2N
SH2N
H2N
N X
N
N
MeMe
Me
MeOH
HN N
Bu
SMe
Ph
2Br–
2Cl–
Me2N
S NMe2
Me2N NMe2
SMe
Br–
Cl Cl
S S NH2
NH2
H2N
H2N
N NBu
S
HH
Ph
NX
OH
Me
NN
SeI–
NN
X
X Br
OS
S NMe2
NMe2
Me2N
Me2N
75 X = O 76 X = S
73 X = O74 X = S
N N
P
PMe
HH
O–OH
ONaO OH
SMe
+
62 X = O, 63 X = S
Br
–
2Cl–
+
+
+
+
BF4–
+ I–+
+
79 X = Se, 80 X = O
+
++
57 58 59
64 6566 67
68 69 7071
7277 78
81
+
60 X = O, 61 X = S
+
+
O
6.23.1.8 Cations Bearing Three Nitrogen Functions
Preparative methods for guanidines have been described in Chapter 6.21. Guanidines are strongbases and also excellent nucleophiles. Several guanidium salts have been prepared by protonationor alkylation of guanidine <1996JPR403>. Tris(pyrrolidine)carbenium chloride 83 has beenprepared from fluorobis-(1-pyrrolidinyl)carbenium chloride 11 by reacting with pyrrolidine<1996JPR403>. Reaction of phenylbis(3-aminobenzene)phosphine 84 with dimethylcyanamide85 provided guanidinium phosphines 86 in high yield <1997JOC2362>. Deprotonation ofPhCOCHPhCO2Me 87 with tetrakis(dimethylamine)methane led to a stable salt 88, which belongsto a very rare species of salts that consists of a heteroatom stabilized carbocation and a heteroatomstabilized carbanion <1996MI2131>.
Triazidocarbenium salt is prepared from tetrachloromethane using NaN3 <1997JA8802>, and 89is ideally suited for high energy density material such as propellants and explosives. Conversion of89 to more energetic salts containing anions such as [�N(NO2)2] and (ClO4
�)] has been reported<1997JA8802>. Quinolinotriazole-N-oxide 90 was converted into the corresponding guanidiniumsalt 91 using 10 <2001OL2793>.
720 Tricoordinated Stabilized Cations, Anions, and Radicals
6.23.1.9 Cations Bearing Nitrogen and Other Element Functions
N,N-Dimethylformamide acetal reacted with elemental selenium to give selenocarbonic acidderivative 92, which was further converted into N,N-dimethylcarbamidic acid Se-methylester93 via alkylation with MeI <1996JPR403>. Alkylation of N-methylbenzoselenazole-2-thione 94and 3,3-ethylenebis(benzoselenoazole-2-thione) 96 with the strong alkylating agent, diethoxy-carbonium tetrafluoroborate, produced corresponding salts 95 and 97, respectively<2002JCS(P1)1568>.
+C(NMe2)3
MeO
Me2NSe
MeN
MeCN
P C N
Se
N N
Se
S
S
NN
Li2–
O+
Li2–O+
N N
Ph
Ph
O
OMe
–O
MeO
Me2NSeMe
I–
SbCl6–
N3 N3
N3
2BF4–
P C N
PPh
NHHN
NMe2Me2NMe2N NMe2
N CN
N
Se
N
N
SeS
S
Se
NS
Me
N NN
N
OH
MeO OMe
S
H2N PPh
NH2
O
Ph
Ph
O
OMe
Se
NMe
S
MeO OMe
SMe
P CBF4
–
N
N
O–
N
Me2N
NMe2
N N
BF4–
X–
PF6–
+
Cl–+
+
+
2Cl–
+ +
+
+
+
++
++
–
..
90 91
+
92 93 94 95
9697
98a98
+
99 100
82
87
8889
8384
8586
Tricoordinated Stabilized Cations, Anions, and Radicals 721
Few cationic carbene complexes and their salts have been prepared in which the cation bearsnitrogen and one phosphorus functions. Synthesis, structure, stability, and reactivity of (amino)(phosphino) carbenes has been reported <2002JA6806>. Treatment of carbene, [(t-Bu)2PCN(i-Pr)2] 98 with 1 equiv. of BF3�Et2O, led to quantitative formation of carbene complex 98a,which has been characterized by NMR spectroscopy <2002JA6806>.
Carbenium ion 100 bearing sulfur and two oxygen functions has been produced via S-alkylationof thiocarbonic acidO,O0-dimethyl ester 99 with iodomethane<1995JOC2330>.
6.23.1.10 Cations Bearing Phosphorus and Silicon Functions
The C-alkylation of 1,3-diethyl-4,5-dimethylimidazol-2-ylidene 101 with iodotrimethylsilane produced1,3-diethyl-4,5-dimethyl-2-(trimethylsilyl)imidazolium iodide 102 <1995CB245>. Rapid valence iso-merization of phosphaalkene-phosphenium cation 103a to cationic diphosphene 103b was observedand 103b was characterized by 31P NMR spectroscopy, but not isolated <1991TL2775>.
1,2-Silyl migration in aromatic carbenes via intermolecular silyl exchange has been reported<1998JA9100>. Since aromatic carbenes are very good nucleophiles, attack of triphenyltriazolecarbene 104 on the silyl group of cation 105 resulting in the formation of C-silyl substitutedtriazolium salt 106 along with methyltriazole <1998JA9100>. Several crystalline adducts109 were prepared from benzimidazole carbene 107 by reacting with derivatives of 108(silylene germylene, stannylene, or plumbylene). The C�M bond is electrostatic in nature withthe carbene moiety as an electron donor and the metal fragment as an electron acceptor<2000JCS(D)3094>.
N N
NPhPh
Ph
SiMe
MeN
N
N
Ph
Ph
Ph N
N NMe
SiMe
Me
CF3SO3–
CF3SO3–+
..+
104 105 106
N
NM –
N
N
N
N
MN
N+
109 M = Si, Ge, Sn, Pb108 M = Si, Ge, Sn, Pb
..
107
N
NEt
EtN
NEt
Et
SiMe
Me I– Et2N
Et2NP P N
CF3SO3–
Me
CF3SO3–
Et2N
Et2NP P N+
102 103b
+
101
.. +
103a
6.23.2 CARBON-CENTERED CARBANIONS BEARINGTHREE HETEROATOM FUNCTIONS
Carbanionic carbons bearing three different heteroatom functions were not covered in the earlierreview <1995COFGT(6)725>. The current review includes several such carbanionic carbon-
722 Tricoordinated Stabilized Cations, Anions, and Radicals
bearing nitrogen, phosphorus, and sulfur functions. They are stable at low temperature, isolable,and are useful intermediates in organic synthesis. Attachment of phosphorus and sulfur functionsto carbanionic carbon causes an increase in carbanion stability due to an overlap of the unsharedelectron pair with an empty d-orbital (p��d� bonding). Electron withdrawing groups such asNO2 at the �-position also stabilize carbanions.
6.23.2.1 Carbanion Bearing Three Halogens
The N-trimethylsilylimidophosphenous acid derivative from 2,2,6,6-tetramethylpiperidine reactswith bromotrichloromethane readily to afford the stable salt 110. The ion pair 110 is stable andprovides an environment for sterically favorable nucleophilic substitution of the trichloromethideanion rather than bromide ion. The possibility that this reaction proceeds via a radical mechanismcannot be ruled out <1984JGU278>.
6.23.2.2 Carbanions Bearing One Halogen and Two Sulfur Functions
The 2,2,4,4-tetrabromo-1,3-dithietan-1,1,3,3-tetroxide 111 is cleaved by tris(dimethylamine)sulfoniumhexafluoride silicate 112 to form the intermediate salt 113. The fluoride ion from 113 can be abstractedby SiF4 and quinuclidine and the resulting perhalogenatedmesylsulfene (Br3SO2C(Br)¼SO2 is stabilizedby S-coordinated quinuclidine <1990ZN(B)1187>.
6.23.2.3 Carbanions Bearing One Halogen and Two Phosphorus Functions
Phosphonoalkylation of acylchlorophosphinate 114 in the presence of excess of LDA leads todirect generation of stable lithiated methylenediphosphonate anion 115. Further 115 can be eitherprotonated in acidic medium to provide tetrasubstituted methylenediphosphonate or alkylated.When aliphatic or aromatic aldehydes are added, spontaneous formation of vinyl phosphonates isobserved <1986JOMC(304)283>.
6.23.2.4 Carbanions Bearing Three Nitrogen Functions
Deprotonation of trinitromethane with tetrabutylammonium hydroxide results in trinitromethide116a. Deprotonation of trinitromethane with benzyltrimethylammonium hydroxide provides116b, which is unstable even at �15 �C and it undergoes decomposition with explosive releaseof gases when stored in the dark at room temperature <1985JA7880>.
6.23.2.5 Carbanions Bearing Three Sulfur Functions
Interaction of tris(fluorosulfonyl)methane and tris(trifluoromethylsulfonyl) with aryldiazoniumchloride in water leads to the formation of stable water-insoluble salts 117a and 117b, respectively<1983TL87, 1990JOU584>. Benzenediazonium bis(fluorosulfonyl)phenoxysulfonyl methanide 118,a colorless crystalline solid stable at 0 �C is produced by simple mixing of benzenediazonium chloridewith bis(fluorosulfonyl)phenoxysulfonylmethane <1991JOU426>.
6.23.2.6 Carbanions Bearing Three Phosphorus Functions
Bis(diphenylphosphino)diphenylthiophosphorylmethane is readily deprotonated with LiOH toproduce the carbanion 119 <1988PS79>. Tetrabutylammonium tris(diphenylthiophosphinoyl)-methide 120 has been produced from tris(diphenylthiophosphinoyl)methane and isolated as astable solid, which is a useful synthetic intermediate in the formation of cage complexes viacoordination with metal cations <1982CC930>.
Tricoordinated Stabilized Cations, Anions, and Radicals 723
6.23.2.7 Carbanions Bearing One Phosphorus and Two Sulfur Functions
Deprotonation of bis(ethylsulfanylmethyl) phosphonic acid diethyl ester and of bis(benzenesulfo-nyl)-diphenyloxoposphinyl methane produces salts 121 and 122, respectively <1982TL499,1987PS159>. Trifluoromethylsulfonylphenylsulfonyldiphenylphosphinoyl methane reacts withtriphenylphosphine to form salt 123, which is protonated on the phosphorus. However, withdiphenylphosphinous acid, diethylamideaminophosphine affords phosphonium salt 124, which isprotonated on the nitrogen <1977JGU872>.
6.23.2.8 Carbanions Bearing One Nitrogen and Two Sulfur Functions
Bis(phenylsulfonyl)diazomethane is a possible source for the production of an exceptionallyelectrophilic carbene, bis(phenylsulfonyl)carbene and its chemical properties were studied in thelate 1990s. Treatment of bis(phenylsulfonyl)diazomethane with triphenylphosphine yields thestable phosphazine 125 <1963JOC2933>.
6.23.3 CARBON-CENTERED RADICALS BEARING THREEHETEROATOM FUNCTIONS
A few known stable carbon-centered radicals bearing three heteroatom functions have beenreviewed <1995COFGT(6)725>. No carbon-centered radicals bearing three heteroatom functionscan be regarded as ‘‘stable’’ in that they cannot be isolated and handled. But a few such radicalshave significant lifetimes ranging from a few seconds to a few hours in solution <1976ACR13>.These radicals bear silicon, phosphorus, or sulfur substitutents and their increased lifetime can bedue to steric factors rather than to electron delocalization.
N PBr
N Si
OP
O
ClO
OOP
OPOEtO
Cl
SS
BrBr
BrBr
OO
OO
Cl
Cl Cl
P
Ph2P PPh2
SPhPh
NMe2
SMe2N NMe2
OEt
SiF6–
Br
FO2S SO2CBr3
+S(NMe2)3
NO2
O2N NO2
SO2X
XO2S SO2X
SO2Ph
FO2S SO2F
PhN2+
+Li
P
Ph2P PPh2
SPhPh
S S+NBu4
P
EtS SEt
OOEtEtO
PhN2+
P
PhO2S SO2Ph
OPhPh
+NBu4
PPh2
F3CO2S SO2Ph
HPPh3
PPh2
F3CO2S SO2Ph
Ph2PNHEt2
N=NPPh3
PhO2S SO2Ph
PhN2+
Li+
X P
OEt
OEt
SR
SMe
X P
OEt
OEt
S
SMe
+
_
–
110
114 115
111
–
+
112 113
–
117a, X = F; 117b, X = CF3
– –
118
119
–
120
– –
121 122
–
+
123
–+
+
–
124 125
116a = +NBu4
116b = +NCH2PhMe3
.
126 127
–
724 Tricoordinated Stabilized Cations, Anions, and Radicals
The tris(trimethylsilyl)methyl radical _C(TMS)3 can be generated by decomposition of[(TMS)3C]2Hg <1970CC559> or by reduction of (TMS)3CI <1991CC1608>. This radical islong-lived in solution. A number of carbon radicals bearing three sulfur functions can also bedescribed as persistent, among them C(SCF3), which is generated reversibly from its dimer at roomtemperature <1979JA6282>, and_C(SCF3)2SC6F5, which is produced from its dimer at 140–190 �C<1984T4963>. A number of other radicals bearing three sulfur functions or two sulfur and onesilicon functions can be produced by the thermal dissociation of their dimers <1977CB2880>.A series of persistent radicals 126 has been produced by the reaction of the dithioesters 127 with awide range of radicals R_, including MeS_, Me_, and Ph3Pb_<1993JA8444>.
Since 1995, one or two such radicals have been reported in the literature. The reduction ofphosphoryl and thiophosphoryl formates, monothioformates and dithioformates have been studiedby means of cyclic voltametry and electron paramagnetic resonance (EPR) spectroscopy data wereobtained for these salts<2000JCS(P2)1908, 2002MRC387>. Electron transfer reactions were studiedbetween NO� and halotrifluoromethane in the gas phase and the formation of F2CNO radical hasbeen observed <1996JPC10641>.
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726 Tricoordinated Stabilized Cations, Anions, and Radicals
Biographical sketch
Marudai Balasubramanian was born in Trichy, India. He obtained hisB.Sc. from PEVR College/Madras University, Trichy; his M.Sc. degreeat Vivekananda College, Chennai; and his Ph.D. degree in organicchemistry from the Indian Institute of Technology, Chennai, India in1987. He was briefly a Research Associate at ICI India Ltd., India. Hispostdoctoral work was conducted with Dr. A. R. Katritzky, Departmentof Chemistry, University of Florida, Gainesville, FL (1988–1992). Dur-ing this period, he acquired an in-depth knowledge of various aspects ofheterocyclic chemistry and his main research work was concentrated onreactions in hot water. He then worked as a Research Chemist/ResearchAssociate for ten years at Reilly Industries Inc., Indianapolis, IN. Hisresearch interests include synthesis of heterocyclic compounds particu-larly pyridine derivatives, synthesis of intermediates for pharmaceuticals,agrochemicals, performance products, and heterocyclic polymers. In2002, he joined Pfizer Inc, Ann Arbor, MI as an Information Scientistproviding chemistry/patent information to scientists and attorneys.
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Comprehensive Organic Functional Group Transformations 2ISBN (set): 0-08-044256-0
Volume 6, (ISBN 0-08-044258-7); pp 713–727
Tricoordinated Stabilized Cations, Anions, and Radicals 727