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Lutz F. Tietze

Domino Reactions

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Edited by Lutz F. Tietze

Domino Reactions

Concepts for Efficient Organic Synthesis

Editor

Prof. Dr. Lutz F. TietzeGeorg-August UniversityInstitute of Organic and BiomolecularChemistryTammannstr. 237077 GottingenGermany

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V

Contents

Preface XIIIList of Contributors XVList of Abbreviations XIX

Introduction 1References 4

1 Transition-Metal-Catalyzed Carbonylative Domino Reactions 7Xiao-Feng Wu, Helfried Neumann, and Matthias Beller

1.1 Introduction 71.2 Transition-Metal-Catalyzed Carbonylative Domino Reactions 81.2.1 Ruthenium-Catalyzed Carbonylative Domino Reactions 81.2.2 Rhodium-Catalyzed Carbonylative Domino Reactions 131.2.3 Palladium-Catalyzed Carbonylative Domino Reactions 161.2.4 Iron-, Copper-, Nickel-, and Cobalt-Catalyzed Carbonylative Domino

Reactions 241.3 Outlook 27

References 27

2 Metathesis Reactions in Domino Processes 31Kamal M. Dawood and Peter Metz

2.1 Domino Processes Featuring Solely Metathesis Events 312.1.1 Reactions Involving Only Alkenes 312.1.2 Reactions Involving Alkenes and Alkynes 412.2 Domino Processes Featuring Metathesis and Non-metathesis

Events 522.2.1 Metathesis/Redox Transformation 522.2.2 Metathesis/Isomerization 532.2.3 Metathesis/Cycloaddition 562.2.4 Metathesis/Substitution 582.2.5 Metathesis/Conjugate Addition 592.2.6 Metathesis/Carbonyl Olefination 62

VI Contents

2.3 Conclusion and Outlook 63Acknowledgments 63References 63

3 C–H Activation Reactions in Domino Processes 67Gavin Chit Tsui and Mark Lautens

3.1 Heck Reactions/C–H Activations 673.2 Carbopalladations and Aminopalladations of Alkynes/C–H

Activations 723.3 Palladium-Catalyzed/Norbornene-Mediated ortho C–H Activations 803.4 Domino Reactions Involving Heteroatom-Directed C–H

Activations 963.5 Conclusions 101

References 101

4 Domino Reactions Initiated by Nucleophilic Substitution 105Hiriyakkanavar Ila, Anand Acharya, and Saravanan Peruncheralathan

4.1 Domino SN/Michael Addition and Related Reactions 1064.2 Domino Reactions Initiated by Nucleophilic Ring Opening of

Aziridines, Epoxides, and Activated Cyclopropanes 1154.3 Domino SN/Brook Rearrangements 127

References 138

5 Radical Reactions in Domino Processes 141Guanghui An and Guigen Li

5.1 Introduction 1415.2 Radical/Cation Domino Processes 1435.3 Radical/Anionic Domino Processes 1485.4 Domino Radical/Radical Process 1545.5 Radical/Pericyclic Domino Processes 1725.6 Asymmetric Radical Domino Processes 1745.6.1 Chiral Auxiliary-Directed Asymmetric Radical Domino Processes 1745.6.2 Chiral Catalyst-Driven Asymmetric Radical Domino Processes 1765.7 Conclusion and Outlook 178

Acknowledgments 179References 179

6 Pericyclic Reactions in Domino Processes 183Lukas J. Patalag and Daniel B. Werz

6.1 Introduction 1836.2 Cycloadditions 1846.2.1 Cycloaddition/Cycloaddition 1846.2.2 Cycloaddition/Cycloreversion 1856.2.3 Cycloaddition/Sigmatropic Rearrangement 1886.2.4 Cycloaddition/Electrocyclization 189

Contents VII

6.2.5 Cycloaddition/Mixed Transformations 1916.3 Sigmatropic Rearrangements 1926.3.1 Sigmatropic Rearrangement/Sigmatropic Rearrangement 1926.3.2 Sigmatropic Rearrangement/Cycloaddition 1956.3.3 Sigmatropic Rearrangement/Electrocyclization 1966.3.4 Sigmatropic Rearrangement/Mixed Transformations 1996.4 Electrocyclizations 2016.4.1 Electrocyclization/Electrocyclization 2016.4.2 Electrocyclization/Cycloaddition 2026.4.3 Electrocyclization/Sigmatropic Rearrangement 2056.4.4 Electrocyclization/Mixed Transformations 2086.5 Mixed Transformations 2096.5.1 Mixed Transformations Followed by Pericyclic Reactions 2096.5.2 Cascades of Carbopalladations Followed by Pericyclic Reactions 2116.5.3 Domino Knoevenagel/Hetero Diels–Alder Reaction 2146.6 Concluding Remarks 214

Acknowledgments 215References 215

7 Modern Domino Reactions Containing a Michael Addition Reaction 219Scott G. Stewart

7.1 Introduction 2197.2 Formation of Acyclic Products 2217.3 Formation of Carbocycles 2257.4 Formation of O-Heterocycles 2367.5 Formation of N-Heterocycles 2507.6 Formation of S-Heterocycles 2577.7 Formation of Heterocycles Containing Nitrogen and Oxygen 260

References 262

8 Aldol Reactions in Domino Processes 267Christoph Schneider and Michael Boomhoff

8.1 Introduction 2678.2 Domino Processes with the Aldol Reaction as First Step 2678.2.1 Aldol-Lactonization Reactions 2678.2.2 Aldol/Prins Reactions 2708.2.3 Aldol/Acetalization Reactions 2728.2.4 Aldol–Tishchenko Reactions 2738.2.5 Vinylogous Aldol/Michael Reactions 2768.3 Domino Processes with the Aldol Reaction as Subsequent Step 2778.3.1 Conjugate Addition/Aldol Reactions 2778.3.1.1 Addition of Carbon Nucleophiles 2778.3.1.2 Addition of Sulfur Nucleophiles 2818.3.1.3 Addition of Oxygen and Nitrogen Nucleophiles 2838.3.1.4 Iodo-Aldol Reactions 285

VIII Contents

8.3.1.5 Reductive Aldol Reactions 2878.3.2 Isomerization/Aldol Reactions 2898.3.3 Wittig Rearrangement/Aldol Reactions 2908.3.4 Cycloaddition/Aldol Reactions 2908.4 Conclusion and Outlook 292

References 292

9 Oxidations and Reductions in Domino Processes 295Govindasamy Sekar, Iyyanar Karthikeyan, and Dhandapani Ganapathy

9.1 Introduction 2959.2 Domino Reactions Initiated by Oxidation or Reduction Reaction 2969.2.1 Domino Reactions Initiated by an Oxidation Reaction 2969.2.2 Domino Reactions Initiated by Reduction Reaction 3019.3 Domino Reactions Having Oxidation in Middle of the Sequence 3129.4 Domino Reactions Terminated by Oxidation or Reduction

Reaction 3139.4.1 Domino Reactions Terminated by Oxidation Reaction 3139.4.2 Domino Reactions Terminated by Reduction Reaction 3149.5 Conclusion 319

Acknowledgments 319References 319

10 Organocatalysis in Domino Processes 325Helene Pellissier

10.1 Introduction 32510.2 One- and Two-Component Domino Reactions 32610.2.1 Domino Reactions Initiated by the Michael Reaction 32710.2.1.1 Domino Michael/Michael Reactions 32710.2.1.2 Domino Michael/Aldol Reactions 33410.2.1.3 Domino Michael/Intramolecular Heterocyclization Reactions 34010.2.1.4 Domino Michael/Intramolecular Alkylation Reactions 34910.2.1.5 Domino Michael/(aza)–Henry Reactions 35210.2.1.6 Domino Michael/Knoevenagel Reactions 35510.2.1.7 Domino Michael/aza-Morita–Baylis–Hillman Reactions 35710.2.1.8 Domino Michael/Mannich Reactions 35710.2.1.9 Other Domino Reactions Initiated by the Michael Reaction 35910.2.2 Domino Reactions Initiated by Other Reactions 36110.2.2.1 Domino Reactions Initiated by the Indirect Mannich Reaction 36110.2.2.2 Domino Reactions Initiated by the (Aza)-Morita–Baylis–Hillman

Reaction 36310.2.2.3 Domino Reactions Initiated by the Friedel–Crafts Reaction 36410.2.2.4 Miscellaneous Domino Reactions 36510.3 Multicomponent Reactions 37110.3.1 Multicomponent Reactions Initiated by the Michael Reaction 37110.3.1.1 Michael Reactions of α,β-Unsaturated Aldehydes 371

Contents IX

10.3.1.2 Michael Reactions of Other α,β-Unsaturated CarbonylCompounds 378

10.3.1.3 Michael Reactions of Nitroolefins 38010.3.2 Multicomponent Reactions Initiated by the Knoevenagel Reaction 38510.3.3 Multicomponent Reactions Based on the Mannich Reaction 38810.3.4 Multicomponent Reactions Based on the Biginelli Reaction 39210.3.5 Multicomponent Reactions Based on the Hantzsch Reaction 39410.3.6 Multicomponent Reactions Based on the Strecker Reaction 39510.3.7 Multicomponent Reactions Based on the Petasis Reaction 39710.3.8 1,3-Dipolar Cycloaddition-Based Multicomponent Reactions 39810.3.9 Miscellaneous Multicomponent Reactions 40010.4 Conclusions 405

References 405

11 Metal-Catalyzed Enantio- and Diastereoselective C–C Bond-FormingReactions in Domino Processes 419Shinobu Takizawa and Hiroaki Sasai

11.1 Domino Reaction Initiated by C–C Bond Formation 41911.1.1 Domino Reaction Initiated by Conjugate Addition 41911.1.2 Domino Reaction Initiated by Cycloaddition 43311.1.3 Domino Reaction Initiated by Carbometalation 43511.2 Domino Reaction Initiated by C–H Bond Formation 43511.2.1 Domino Reaction Initiated by Conjugate Addition 43511.3 Domino Reaction Initiated by C–N Bond Formation 44211.3.1 Domino Reaction Initiated by Imine Formation 44211.3.2 Domino Reaction Based on Cycloaddition 44311.4 Domino Reaction Initiated by C–O Bond Formation 44511.4.1 Domino Reaction Initiated by Carbonyl Ylide Formation 44511.4.2 Domino Reaction Initiated by Oxonium Ylide Formation 45011.4.3 Domino Reaction Based on Cycloaddition 45211.4.4 Domino Reaction Based on Pd(II)/Pd(IV) Catalysis 45411.4.5 Domino Reaction Based on a Wacker Oxidation 45411.5 Domino Reaction Initiated by C–B and C–Si Bond Formation 45511.5.1 Domino Reaction Initiated by Conjugate Addition 45611.6 Conclusion and Outlook 457

References 458

12 Domino Processes under Microwave Irradiation, High Pressure, and inWater 463Bo Jiang, Shu-Jiang Tu, and Guigen Li

12.1 Introduction 46312.2 Microwave-Assisted Domino Reactions 46412.2.1 Intramolecular Domino Reactions under Microwave Heating 46412.2.2 Two-Component Domino Reaction under Microwave Heating 46512.2.3 Multicomponent Domino Reactions under Microwave Heating 472

X Contents

12.3 Aqueous Domino Reactions 48012.3.1 Two-Component Domino Reactions in Water 48012.3.2 Multicomponent Domino Reaction in Water 48412.4 High-Pressure-Promoted Domino Reactions 48912.5 Conclusion and Outlook 491

Acknowledgments 492References 492

13 Domino Reactions in Library Synthesis 497Vincent Eschenbrenner-Lux, Herbert Waldmann, and Kamal Kumar

13.1 Introduction 49713.2 Domino Reactions in Natural-Product-Inspired Compound Collection

Syntheses 49813.2.1 Coinage Metal-Catalyzed Domino Synthesis 49813.2.2 Multicatalytic Domino Processes 50013.2.3 Synthesis of Natural-Product-Inspired Centrocountins Using Domino

Reactions 50313.3 Domino Approaches Targeting Scaffold Diversity 50613.3.1 Substrate-Based Approach: the Metathesis/Metathesis Domino

Process 50713.3.2 Reagent-Based Domino Approaches 50913.3.3 Domino Reactions in the Build–Couple–Pair Approach for Library

Synthesis 51513.4 Solid-Phase Domino Syntheses of Compound Collections 51613.5 Conclusion 519

References 520

14 Domino Reactions in the Total Synthesis of Natural Products 523Svenia-C. Dufert, Judith Hierold, and Lutz F. Tietze

14.1 Cationic Domino Reactions 52314.2 Anionic Domino Reactions 53314.3 Radical Domino Reactions 54914.4 Pericyclic Domino Reactions 55114.5 Transition-Metal-Catalyzed Domino Reactions 55414.6 Domino Reactions Initiated by Oxidation or Reduction 56814.7 Conclusion 571

References 572

15 Multicomponent Domino Process: Rational Design and Serendipity 579Qian Wang and Jieping Zhu

15.1 Introduction 57915.2 Basic Considerations of MCRs 58115.3 Substrate Design Approach in the Development of Novel MCRs 58315.3.1 Chemistry of α-Isocyanoacetates 58315.3.2 From α-Isocyanoacetates to α-Isocyanoacetamides 585

Contents XI

15.3.3 From α-Isocyanoacetamides to α-Isocyanoacetic Acids 58915.3.4 Back to α-Isocyanoacetates 59015.3.5 Chemistry of Oxazoles 59315.3.5.1 Dienophile as an Additional Component 59315.3.5.2 Using Dienophile-Containing Inputs 59715.3.6 Serendipity 60115.3.6.1 Groebke–Blackburn–Bienayme Reaction 60115.3.6.2 One-Carbon Oxidative Homologation of Aldehydes to Amides 60215.3.6.3 One-Carbon Oxidative Homologation of Aldehydes to

α-Ketoamides 60415.4 Conclusion 607

References 607

Index 611

XIII

Preface

The synthesis of chemical compounds is a key issue in chemistry, both in academiaand industry. A simple statement of general relevance is the saying ‘‘you cannotinvestigate a compound which you do not have in your hands and you cannotsell a substance which you did not make.’’ However, the aspects of synthesis havechanged over the years. At the beginning, the development of synthetic methodssuch as the electrophilic aromatic substitution, the aldol reaction or the Diels–Aldercycloaddition was in the focus. Then the selectivity as the chemo-, regio-, diastereo-,and enantioselectivity was the main concern. Now, new aspects in synthesis havearisen, which are part of green chemistry: efficiency, reduction of waste, saving ourresources, protecting our environment, and, finally, also economic advantages byreducing the transformation time and the amount of chemicals needed. To meetall these requirements, the domino concept was introduced by me, which, since itspresentation and the first reviews, has grown immensely in the last years. In thisbook, experts in the different fields of domino reactions have put together theirknowledge, and I am very grateful to all of them for their excellent contributions.Moreover, I would like to thank Martina Pretor for her fabulous help in preparingthe book. I am also grateful to the publishers Wiley/VCH, especially Dr. Elke Maaseand Dr. Bernadette Gmeiner, for their support.

Finally, I would like to express my deep thanks to the University of Gottingen,the State of Lower Saxony, the German Research Foundation (DFG), the Volkswa-gen Foundation, the German Ministry of Education and Research (BMBF), theEuropean Community and the Fonds der Chemischen Industrie as well as theAlexander von Humbold Foundation, the Konrad–Adenauer–Foundation and theGerman National Academic Foundation for their continuous support of our workon domino reactions and other topics. I am also very thankful to many ChemicalCompanies worldwide, in particular the BASF and the Bayer AG.

Gottingen, June 6th, 2013 Lutz F. Tietze

XV

List of Contributors

Anand AcharyaNew Chemistry UnitJawaharlal Nehru Centre forAdvanced Scientific ResearchJakkurBangalore 560 064KarnatakaIndia

Guanghui AnTexas Tech UniversityDepartment of Chemistry andBiochemistryStreet Boston and BroadwayLubbockTX, 79409-1061USA

Matthias BellerLeibniz Institute for CatalysisAlbert-Einstein-Str. 29a18059 RostockGermany

Michael BoomhoffUniversity of LeipzigInstitute of Organic ChemistryJohannisallee 2904103 LeipzigGermany

Kamal M. DawoodTechnische Universitat DresdenDepartment of ChemistryBergstrasse 6601069 DresdenGermany

Svenia-C. DufertGeorg-August UniversityInstitute of Organic andBiomolecular ChemistryTammannstr. 237077 GottingenGermany

Vincent Eschenbrenner-LuxMax Planck Institute of MolecularPhysiologyOtto-Hahn-Str. 1144227 DortmundGermany

Dhandapani GanapathyIndian Institute of TechnologyMadrasDepartment of ChemistryChennai 600 036Tamil NaduIndia

XVI List of Contributors

Judith HieroldGeorg-August UniversityInstitute of Organic andBiomolecular ChemistryTammannstr. 237077 GottingenGermany

Hiriyakkanavar IlaNew Chemistry Unit JawaharlalNehru Centre for AdvancedScientific ResearchJakkurBangalore 560 064KarnatakaIndia

Bo JiangJiangsu Normal UniversitySchool of Chemistry andChemical EngineeringShanghai Road 101New District of TongshanXuzhou, 221116P. R. China

Iyyanar KarthikeyanIndian Institute of TechnologyMadrasDepartment of ChemistryChennai 600 036Tamil NaduIndia

Kamal KumarMax Planck Institute of MolecularPhysiologyOtto-Hahn-Str. 1144227 DortmundGermany

Mark LautensDavenport Research LaboratoriesUniversity of TorontoDepartment of Chemistry80 St. George St.TorontoON M5S 3H6CanadaUSA

Guigen LiTexas Tech UniversityDepartment of Chemistry andBiochemistryStreet Boston and BroadwayLubbockTX, 79409-1061USA

and

Nanjing UniversityInstitute of Chemistry &BioMedical Sciences22 Hankou RoadNanjing 210093P. R. China

Peter MetzTechnische Universitat DresdenDepartment of ChemistryBergstrasse 6601069 DresdenGermany

Helfried NeumannLeibniz Institute for CatalysisAlbert-Einstein-Str. 29a18059 RostockGermany

List of Contributors XVII

Lukas J. PatalagTechnical University ofBraunschweigInstitute of Organic ChemistryHagenring 3038106 BraunschweigGermany

Helene PellissierAix Marseille UniversiteCNRS, iSm2 UMR 731313397 MarseilleFrance

Saravanan PeruncheralathanNational Institute of ScienceEducation and ResearchInstitute of Physics CampusSchool of Chemical SciencesBhubaneswar 751 005OrissaIndia

Hiroaki SasaiOsaka UniversityThe Institute of Scientific andIndustrial Research (ISIR)Mihogaoka Ibaraki-shiOsaka 567-0047Japan

Christoph SchneiderUniversity of LeipzigInstitute of Organic ChemistryJohannisallee 2904103 LeipzigGermany

Govindasamy SekarIndian Institute of TechnologyMadrasDepartment of ChemistryChennai 600 036Tamil NaduIndia

Scott G. StewartThe University of WesternAustraliaSchool of Chemistry andBiochemistry35 Stirling HighwayCrawleyWA 6009Australia

Shinobu TakizawaOsaka UniversityThe Institute of Scientific andIndustrial Research (ISIR)Mihogaoka Ibaraki-shiOsaka 567-0047Japan

Lutz F. TietzeGeorg-August UniversityInstitute of Organic andBiomolecular ChemistryTammannstr. 237077 GottingenGermany

Gavin Chit TsuiMax-Planck-Institut furKohlenforschungKaiser-Wilhelm-Platz 145470 Mulheim an der RuhrGermany

XVIII List of Contributors

Shu-Jiang TuJiangsu Normal UniversitySchool of Chemistry andChemical EngineeringShanghai Road 101New District of TongshanXuzhou, 221116P. R. China

Herbert WaldmannMax Planck Institute of MolecularPhysiologyOtto-Hahn-Str. 1144227 DortmundGermany

Qian WangEcole Polytechnique Federale deLausanneInstitute of Chemical Sciencesand Engineering1015 LausanneSwitzerland

Daniel B. WerzTechnical University ofBraunschweigInstitute of Organic ChemistryHagenring 3038106 BraunschweigGermany

Xiao-Feng WuLeibniz Institute for CatalysisAlbert-Einstein-Str. 29a18059 RostockGermany

Jieping ZhuEcole Polytechnique Federale deLausanneInstitute of Chemical Sciencesand Engineering1015 LausanneSwitzerland

XIX

List of Abbreviations

(S,S)-MeDuPhos (+)-1,2-bis[(2S,5S)-2,5-dimethylphospholano]benzene(TMS)2NH hexamethyldisilazane or bis(trimethylsilyl)amine[Bmim] 1-butyl-3-methylimidazoliumAc acetylacac acetylacetoneACCN 1,1′-azobis(cyclohexanecarbonitrile)Ac2O acetic anhydrideAcOH acetic acidAIBN 2,2′-azobisisobutyronitrileAll allylAr arylARC anionic relay chemistryASG anion stabilizing groupATBT allyltri-n-butyltinatm standard atmosphereBAIB (diacetoxyiodo)benzeneBER borohydride exchange resinBF3·OEt2 boron trifluoride–diethyl ether complexBHT butylhydroxytolueneBINAP 2,2′-bis(diphenylphosphino)-1,1′-binaphthaleneBINAPO 2-diphenylphosphino-2′-diphenylphosphinyl-1,1′-

binaphthaleneBINOL 1,1′-bi-2-naphtholBiphep 1,1′-biphenyl-2,2′-diphenylphosphineBn benzylBoc tert-butoxycarbonylborsm based on recovered starting materialbpz 2,2′-bipyrazineBu butylBz benzoylCA cycloadditionCAN ceric ammonium nitrate

XX List of Abbreviations

Cbz carbonylbenzyloxyCD circular dichroismcf . compare (lat. confer)CM cross-metathesiscod 1,5-cyclooctadienecoe cycloocteneCp cyclopentadienylCR cycloreversionCSA camphorsulfonic acidCy cyclohexyld dayDA Diels–Alder reactionsDABCO 1,4-diazabicyclo[2.2.2]octaneDAIB (diacetoxyiodo)benzenedba dibenzylidenacetoneDBU 1,8-diazabicyclo[5.4.0]undec-7-eneDCB 1,2-dichloroisobutaneDCE 1,2-dichloroethaneDCM dichloromethaneDDQ 2,3-dichloro-5,6-dicyano-1,4-benzoquinonede diastereomeric excessDFT density functional theoryDHQ hydroquinineDHQD dihydroquinidineDIBAL diisobutylaluminum hydrideDIOP 4,5-bis(diphenylphosphinomethyl)-2,2-dimethyl-1,3-dioxolaneDIPEA diisopropylethylamineDKP diketopiperazineDLP 1,2-dichloroethane with lauroyl peroxideDMA N,N-dimethylacetamideDMAD dimethyl acetylenedicarboxylateDME dimethoxyethaneDMF N,N-dimethylformamideDMP Dess–Martin-periodinaneDMPU 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone,

N,N-dimethyl propylene ureaDMSO dimethyl sulfoxideDOS diversity-oriented synthesisdpm dipivaloylmethanedppe 1,2-bis(diphenylphosphino)ethanedppf 1,2-bis(diphenylphosphino)ferrocenedppp 1,3-bis(diphenylphosphino)propanedr diastereomeric ratioDTBP 2,6-di-tert-butylpyridineE electrophile

List of Abbreviations XXI

EC electrocyclizationee enantiomeric excessequiv equivalentERO electrocyclic ring-openinget al. and others (lat. et alii)Et ethylEWG electron-withdrawing groupFmoc 9-fluorenylmethoxycarbonylfod (6,6,7,7,8,8,8-heptafluoro-2,2-dimethyloctane-3,5-dionateGAP group-assisted purificationh hourHAT hydrogen atom transferHFIP hexafluoroisopropanolHIV human immunodeficiency virusHMPA hexamethylphosphortriamideHOMO highest occupied molecular orbitali.e. that means (lat. id est)IBX 2-iodoxybenzoic acidIMDA intramolecular Diels–Alder reactionL ligandLDA lithium diisopropylamideLiHMDS lithium hexamethyldisilazideLUMO lowest unoccupied molecular orbitalMAOS microwave-assisted organic synthesisMBH Morita–Baylis–HillmanMDRs multicomponent domino reactionsMe methylMeCN acetonitrileMEK methyl ethyl ketoneMEM (2-methoxyethoxy)methylMes mesitylMOM methoxymethylMTM methylthiomethylMW microwaveNADH nicotinamide adenine dinucleotideNBS N-bromosuccinimideNCS N-chlorosuccinimideNMM N-methyl morpholineNMO N-methylmorpholine-N-oxideNMP N-methyl-2-pyrrolidinoneNs p-nitrobenzenesulfonylNu nucleophileOct octylo-DCB ortho-dichlorobenzenePCC pyridinium chlorochromate

XXII List of Abbreviations

PET photochemical electron transferPEG polyethylene glycolPFBA pentafluorobenzoic acidPG protecting groupPh phenylPhen 9,10-phenanthrolinePhMe toluenePIDA phenyliodine diacetatePiv pivalatePMB p-methoxybenzylPNO pyridine-N-oxidePPh3 triphenylphosphinePPTS pyridinium p-toluenesulfonatePr propylPS–BEMP polystyrene–(2-tert-butylimino-2-diethylamino-1,-dimethyl-

perhydro-1,3,2-diazaphosphorine)PS–DMAP polystyrene–dimethylaminopyridinep-TsOH or p-TSA p-toluenesulfonic acidPVE propargyl vinyl etherPy pyridineR restrac racemicRCM ring-closing metathesisROM ring-opening metathesisRRM ring-rearrangement metathesisrt room temperatureSEM 2-trimethylsilylethoxymethylSET single electron transfersigR sigmatropic rearrangementSN nucleophilic substitutionSN1 substitution nucleophilic unimolecularSN2 substitution nucleophilic bimolecularSolFC solvent free conditionSOMO singly occupied molecular orbitalSPPS solid-phase peptide synthesist tertTADDOL (−)-(4R,5R)- or (+)(4S,5S)-2,2-dimethyl-α,α,α′,α′-tetraphenyl-

1,3-dioxolane-4,5-dimethanolTBA tetra-n-butylammoniumTBA tribromoacetic acidTBAB tetra-n-butylammonium bromideTBAF tetra-n-butylammonium fluorideTBAI tetra-n-butylammonium iodideTBCHD 2,4,4,6-tetrabromo-2,5-cyclohexadienoneTBD 1,5,7-triazabicyclo[4.4.0]dec-5-ene

List of Abbreviations XXIII

TBDMS or TBS tert-butyldimethylsilylTBDPS or TBPS tert-butyldiphenylsilylt-Bu tert-butylt-BuOH tert-butyl alcoholt-BuOK tert-butylate potassiumTC thiophene-2-carboxylateTEA triethylamineTEBA benzyltriethylammonium chlorideTEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyTES triethylsilylTESOTf triethylsilyltrifluoromethanesulfonateTf trifluoromethanesulfonylTFA trifluoroacetic acidTFE 2,2,2-trifluorethanolTfO trifluoromethanesulfonateTFP tri-(2-furyl)phosphineTHF tetrahydrofuranTMSOTf trimethylsilyl trifluromethanesulfonateThio thiopheneTIPS triisopropylsilylTMEDA tetramethylethylendiamineTMS trimethylsilylTMSI trimethylsilyl iodide or iodotrimethylsilaneTol tolylTs 4-toluenesulfonyl (tosyl)TS transition stateTsOH p-toluenesulfonic acidTTMSS tris(trimethylsilyl)silaneVAPOL 2,2′-diphenyl-(4-biphenanthrol)vs. as opposed to (lat. versus)XPhos 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl

1

Introduction

The beginning of organic synthesis can be dated back to the year 1824 whenWohler, later professor of chemistry at the Georg-August University in Gottingen,showed that inorganic matter could be transformed into organic matter without thevis vitalis, the so-called power of life. At that time, he prepared the natural productoxalic acid from dicyan by simple hydrolysis. Better known is the transformationof ammonium cyanate into urea by simple heating, in 1828 (Scheme 1) [1].

A second milestone in organic synthesis is the total synthesis of the indolealkaloid reserpine by Woodward in 1956 [2] using a Diels–Alder reaction as the keystep (Scheme 2), and finally with the total synthesis of palytoxin in 1994, the toxinof dinoflagellate Ostreopsis siamensis, with 64 stereogenic centers and several (E)-and (Z)-double bonds, Kishi [3] has shown that chemists can prepare any organiccompound (Scheme 3).

However, the synthesis of such a big molecule as palytoxin using a conventionalstepwise approach with more than 100 steps is a singular great feat and can almostnot be repeated. Thus, a 100-step synthesis with 80% yield per step would lead toonly 0.00 000 002% as the total yield.

In contrast, a much better efficiency could be accomplished using dominoreactions, which have been defined by us as processes of two or more bond formingreactions under identical reaction conditions, in which the latter transformationstake place at the functionalities obtained in the former bond forming reactions[4]. In the processes one, two, three, or more substrates can be involved. Thus,multicomponent transformations are domino reactions per definition. In themeantime, several excellent reviews have also been published by other authors onthis topic [5].

The quality and the usefulness of domino reactions are related to the increaseof complexity and diversity in the final product compared to the starting material.Thus, the more steps a domino-process includes the greater is the probability totransform simple substrates to huge compounds. A further great advantage of thedomino concept is its benefit to our environment and our natural resources, as itallows reducing the waste produced compared to normal procedures and minimizethe amount of chemicals required for the preparation of a product. This also makesthem economically favorable; moreover, they grant a decrease of the productiontime, which altogether would reduce furthermore the costs of any product.

Domino Reactions: Concepts for Efficient Organic Synthesis, First Edition. Edited by Lutz F. Tietze.© 2014 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2014 by Wiley-VCH Verlag GmbH & Co. KGaA.

2 Introduction

COOH

COOH

C

C

N

N

Hydrolysis

N C O− NH4+

ΔO

NH2

NH2

1824

1828

Scheme 1 Synthesis of oxalic acid and urea without a vis vitalis by Wohler.

NH

N

O

O

OMe

OMe

OMe

OMe

MeO2C

H

H

HMeO

Reserpin (16 steps)

MeO NH

NH2

CHOMeO2C

O

O

OMe

MeO2C

O

O

MeO

O

+

Diels–Alder

Scheme 2 Synthesis of the indole alkaloid reserpine by Woodward 1956.

Domino reactions usually show a good stereocontrol and good overall yields.Also very important is the fact that novel pathways can be developed, which cannotbe followed in a stepwise approach, as in domino reactions intermediates can beunstable compounds, which are consumed as they are formed in a further step.

In our previous book on domino reactions [4h], we have classified domino reac-tions according to the mechanism of the different steps. This organizing principalwill also be used in this book, and you will find chapters about transition metalcatalysis including carbonylation, metathesis and CH-activation, nucleophilic sub-stitutions, radical reactions, pericyclic reactions, Michael reactions, aldol reactions,oxidations, and reductions.

Introduction 3

OO

OH

OH

O

HO

OH

OH

O

H2NOH

OH

HO

OH

OH

OH

OH

OH

O

OH

OH

OH

OH

HO

OOH

OHHO

H

OH

OHOH

OOH

OH

OH

HO

OO

OH

OH

OHHO

OHO

H

OH

OH

HOHO

OH

OH

OH

NH

OO

NH

HO

115

99

98

85

84

77

7675

53

52

51

38

37

23

22

87

1

Palytoxin (>100 steps)

Scheme 3 Synthesis of palytoxin by Kishi 1994.

In addition, we have also included chapters that are related to the type of processas organocatalysis, enantio- and diastereoselective reactions, and multicomponentreactions as well as domino processes under microwave irradiation, high pressure,and in water. Finally, two chapters that are more product oriented have beenincluded on the synthesis of compound collections and the synthesis of naturalproducts and analogs.

This arrangement clearly leads to some overlap, which we have tried to minimizeby discussing related subjects in-depth only in one chapter. However, to allow acorrelation, some domino-processes are mentioned in more than one chapter.

Besides giving information to the reader about the development of dominoreactions in the past years, the main purpose of this book is also to stimulate thedesign of novel domino reactions and use them in the synthesis of natural productsand analogs, pharmaceuticals, agrochemicals, polymers, and materials not only inacademic institutions but also in industry.

Per definition, all domino reactions take place in one reaction vessel withoutisolating any intermediates; however, they are much more than the so-called one-pot reactions, where you just put together different substrates and reagents aftereach other. The planning of domino reactions is like playing chess, where to be areasonable player you will have to analyze four to five steps in advance. Thus, youhave to predict the reaction pathways of all substrates and intermediates in yourreaction mixture and in contrast to chess, where the movement of the differentchess pieces is fixed, the reactivity of the chemical compounds can even be altered,for instance, by changing the pH-value or using different catalysts.

For the use and design of domino reactions in the synthesis of natural products, itis sometimes useful to look at the biosynthesis of these compounds. Thus, Natureis also using the concept of domino reactions and one of the most impressive

4 Introduction

examples is the biosynthesis of lanosterol from (S)-2,3-oxidosqualene, in whichfour new rings and six new stereogenic centers are formed [6]. This concept haslater been exploited by developing a biomimetic synthesis of steroids [7] (Scheme 4).

O

(S)-2,3-Oxidosqualene

HO

H

Lanosterol

Enzyme

Scheme 4 Biosynthesis of lanosterol from (S)-2,3-oxidosqalene.

Another well-known example is the biosynthesis of atropine within the formationof the central skeleton tropinone. Using a twofold Mannich reaction, tropinone hasbeen prepared in a single process [8] (Scheme 5).

CHO

CHO

+ H2N–Me

CO2H

CO2H

O+

MeN

O

Scheme 5 Biomimetic synthesis of tropinone.

It should be stated that the book does not aim at comprehensiveness but theauthors of the different chapters have looked for the most impressive examples andfor clarifying the concept.

References

1. (a) Wohler, F. (1828) Ann. Phys. Chem.,88, 253–256; (b) Wohler, F. (1824) Z.Physiol., 1, S. 125–290.

2. Woodward, R.B. (1958) Tetrahedron, 2,1–57.

3. Suh, E.M. and Kishi, Y. (1994) J. Am.Chem. Soc., 116, 11205–11206.

4. For domino reactions, see: (a) Tietze, L.F.and Beifuss, U. (1993) Angew. Chem. Int.Ed., 105, 137–170 ; Angew. Chem., Int.Ed. Engl. 1993, 32, 131–163; (b) Tietze,L.F. (1996) Chem. Rev., 96, 115–136;(c) Tietze, L.F. (1997) Nachr. Chem.Tech. Lab., 45, 1181–1187; (d) Tietze,L.F. and Lieb, M. (1998) Curr. Opin.Chem. Biol., 2, 363–37; (e) Tietze, L.F.and Haunert, F. (2000) in StimulatingConcepts in Chemistry (eds M. Shibasaki,J.F. Stoddart, and F. Vogtle), Wiley-VCHVerlag GmbH, Weinheim, pp. 39–64;

(f) Tietze, L.F. and Modi, A. (2000) Med.Res. Rev., 20, 304–322; (g) Tietze, L.F.and Rackelmann, N. (2004) Pure Appl.Chem., 76, 1967–1983; (h) Tietze, L.F.and Rackelmann, N. (2005) in Multi-component Reactions (eds J. Zhu and H.Bienayme), Wiley-VCH Verlag GmbH,Weinheim, pp. 121–168; (i) Tietze,L.F., Brasche, G., and Gericke, K.M.(2006) Domino Reactions in OrganicSynthesis, Wiley-VCH Verlag GmbH,Weinheim. (j) Tietze, L.F. and Levy, L.(2009) in The Mizoroki–Heck Reaction (ed.M. Oestreich), Wiley-VCH Verlag GmbH,Weinheim, pp. 281–344; (k) Tietze, L.F.,Spiegl, D.A., and Brazel, C.C. (2009)in Experiments in Green and SustainableChemistry (eds H.W. Roesky and D.K.Kennepohl), Wiley-VCH Verlag GmbH,Weinheim, pp. 158–167; (l) Tietze, L.F.