book of abstracts - instytut chemii organicznej pan€¦ · schedule of microsymposium on...
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Book of abstracts
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Schedule of Microsymposium on Asymmetric Synthesis
1000 prof. Petri Pihko – From co-catalysis to dual catalysis: efficiency and
selectivity in organocatalysis Department of Chemistry, University of Jyväskylä, Finland
1100 coffee break 1130 prof. Radovan Sebesta – Diastereoselective and enantioselective
tandem conjugate addition with Mannich reaction Department of Organic Chemistry, Comenius University, Bratislava, Slovakia dr. Karol Kacprzak – Cinchona alkaloids – what they can do beside catalysis? Department of Chemistry, A. Mickiewcz University, Poznań, Poland prof. Mathias Christmann – Evaluation of strategies for the step-efficient assembly of densely functionalized molecules TU Dortmund, Dortmund, Germany
1330 lunch break 1430-1530 poster session
1530 prof. Shū Kobayashi – New dimension of chiral acid and base
catalysis Department of Chemistry, School of Science, The University of Tokyo, Japan
1700 conference dinner
Sponsors:
Institute of Organic Chemistry Polish Academy of Sciences
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TABLE OF CONTENTS
FROM CO-CATALYSIS TO DUAL CATALYSIS: EFFICIENCY AND SELECTIVITY IN ORGANOCATALYSIS
PETRI PHIKO 6
DIASTEREOSELECTIVE AND ENANTIOSELECTIVE TANDEM CONJUGATE ADDITION WITH MANNICH REACTION
RADOVAN SEBESTA 8
CINCHONA ALKALOIDS – WHAT THEY CAN DO BESIDE CATALYSIS?
KAROL KACPRZAK 9
EVALUATION OF STRATEGIES FOR THE STEP-EFFICIENT ASSEMBLY OF DENSELY FUNCTIONALIZED
MOLECULES MATHIAS CHRISTMANN 10
NEW DIMENSION OF CHIRAL ACID AND BASE CATALYSIS SHŪ KOBAYASHI 11
DEVELOPMENT OF CINCHONA ALKALOIDS IN DIRECT ASYMMETRIC ALDOL REACTION OF HYDROXYKETONES
SEBASTIAN BAŚ 13
STEREOCHEMISTRY CONTROL IN GLYCOSYLATION VIA MODIFIED O-2-BENZYL GROUP
SZYMON BUDA 14
STEREOSELECTIVE SYNTHESIS OF LONG-CHAIN CARBOHYDRATES
MACIEJ CIEPLAK 15
SYNTHESIS OF CHIRAL TERTIARY DIAMINES DERIVED FROM (L)-PROLINE AND THEIR APPLICATION IN
ASYMMETRIC CATALYSIS
RAFAŁ ĆWIEK 16
ORGANOCATALYTIC MICHAEL REACTION UNDER HIGH PRESSURE: ASYMMETRIC SYNTHESIS OF γγγγ-
NITROKETONES WITH QUATERNARY STEREOGENIC CENTERS
KRZYSZTOF DUDZIŃSKI 17
BIOMIMETIC SYNTHESIS OF BIOACTIVE 3-DEOXY-ULOSONIC ACID PRECURSORS
OSAMA EL-SEPELGY 18
EFFECT OF PRESSURE ON THE ORGANOCATALYTIC FRIEDEL-CRAFTS REACTION OF INDOLES WITH ENONES
DAWID ŁYśWA 19
AN ENTRY TO CARBAPENAMS VIA ASYMMETRIC KINUGASA REACTION INVOLVING CYCLIC NITRONES AND
TERMINAL ACETYLENES
ADAM MAMES 20
N-HYDROXYPROPARGYLAMINES SYNTHESIS CATALYZED BY NHC COPPER (I) COMPLEXES ON WATER
MICHAŁ MICHALAK 21
LITHIUM – HALOGEN EXCHANGE INITIATED INTRAMOLECULAR ARYLLITHIUM ADDITIONS TO
DIHYDROPYRIDONES
ŁUKASZ MUCHA 22
ASYMMETRIC TRIFLUOROMETHYLATION OF Α-IMINOKETONES DERIVED FROM ARYLGLYOXALS
EMILKA OBIJALSKA 23
AN APPLICATION OF ALIPHATIC NITRONES IN KINUGASA REACTION
KAMIL PARDA 24
ORGANOCATALYTIC ALDOL REACTION – NEW METHOD OF SYNTHESIS IMINOSUGARS
MONIKA PASTERNAK 25
THE MITSUNOBU REACTIONS IN STERICALLY HINDERED MOLECULAR SYSTEMS
AGNIESZKA PAZIK 26
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MICROWAVE-ASSISTED RUTHENIUM CATALYSED OLEFIN METATHESISIN FLUORINATED AROMATIC
HYDROCARBONS: A BENEFICIAL COMBINATION
CEZARY SAMOJŁOWICZ 27
NEW CHIRAL C2-SYMMETRIC LIGANDS WITH THE EASILY ACCESSIBLE DIHYDROANTHRACENE FRAMEWORK
RENATA SIEDLECKA 28
THE COPPER (I) MEDIATED REACTION OF SUGAR-DERIVED NITRONES AND TERMINAL ACETYLENES - AN
APPROACH TO THE SYNTHESIS OF CARBAPENAMS
MAGDALENA SOLUCH 29
CYCLIC IMINE SUGARS – BUILDING BLOCKS IN THE ASYMMETRIC SYNTHESIS OF INDOLIZIDINES
PIOTR SZCZEŚNIAK 30
ACID CATALYST 1,3-DIPOLAR CYCLOADDITION REACTIONS OF SUGAR DERIVED LACTONES WITH DIARYL
NITRONES
MARCIN ŚNIEśEK 31
SYNTHESIS OF 2-VINYL PYRROLIDINES AND PIPERIDINES VIA OVERMANN REARRANGEMENT/CYCLIZATION
SEQUENCE
SEBASTIAN STECKO 32
REGIOSELECTIVE MUKAIYAMA REACTION OF TMS-FURAN IN AQUEOUS MEDIA
MARTA WOYCIECHOWSKA 33
NEW, OPTICALLY ACTIVE IONIC LIQUIDS PREPARED FROM ENANTIOMERICALLY PURE
[1-((S)-PYRROLIDIN-2-YL)METHYL]IMIDAZOLES
ANETA WRÓBLEWSKA 34
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Invited Speakers
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From Co-catalysis to Dual Catalysis: Efficiency and Selectivity in Organocatalysis
Petri M. Pihko Departmenf of Chemistry, University of Jyväskylä, Finland
The use of catalysts bearing multiple hydrogen bond donor (MHBD) groups to increase the catalytic activity via possible formation of several hydrogen bonds, or hydrogen bonds to two different sites, represents an attractive option for enantioselective catalysis.[1-2] Although this approach has been successfully used in multifunctional catalysts where all the necessary functionalities are incorporated in the same catalyst molecule, the use of separate catalysts for electrophile and nucleophile activation might allow more opportunities for catalyst and reaction screening since both catalysts could be optimized separately. As an example, enantioselective enamine catalysts typically incorporate a hydrogen bond donor site (Scheme 1, type A) or rely on steric control alone (type B).[3]
.
Scheme 1.
Scheme 2.
In this presentation, we demonstrate that the use of a dual catalyst system[4] can lead to significant rate enhancements in enamine catalysis and describe the successful use of a dual MHBD/enamine catalyst system for a highly enantioselective domino three-component reaction sequence (Scheme 2). Both steps are catalyzed by the MHBD catalyst as well as the amine catalyst, and two different aldehydes can also be used in a cross-domino sequence, providing the products in excellent enantioselectivity, diastereoselectivity, and high yield. [1] For reviews, see: a) M. Kotke, P. Schreiner, ‘(Thio)urea Organocatalysts.’ In: Hydrogen Bonding in Organic Synthesis,
P. M. Pihko, (Ed.), Wiley-VCH 2009, 141-352, b) Y. Takemoto, Chem. Pharm. Bull. 2010, 58, 593-601. [2] Examples of catalysts bearing multiple hydrogen bond donors: a) C. K. De, E. G. Klauber, D. Seidel, J. Am. Chem.
Soc. 2009, 131, 17060-17061; b) C.-J. Wang, Z.-H. Zhang, X.-Q. Dong, X.-J. Wu, Chem. Commun. 2008, 1431-1433; c) R. P. Herrera, V. Sgarzani, L. Bernardi and A. Ricci, Angew. Chem. Int. Ed., 2005, 44, 6576; d) A. Berkessel, K. Roland and J. M. Neudorfl, Org. Lett. 2006, 8, 4195; e) Z. R. Hou, J. Wang, Z. H. Liu, Z. M. Feng, Chem. Eur. J. 2008, 14, 4484; f) for more examples, see ref 1a.
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[3] For reviews of enamine catalysis, including a discussion of different activation modes, see: a) P. M. Pihko, I. Majander,
A. Erkkilä, Top. Curr. Chem. 2010, 291, 29-75; b) S. Mukherjee, J. W. Yang, S. Hoffman, B. List, Chem. Rev. 2007, 107, 5471-5569; c) For the definition of Type A and Type B catalysts, see: C. Palomo, A. Mielgo, Angew. Chem. Int. Ed. 2006, 45, 7876-7880; d) For a recent review of bulky silylated organocatalysts, see: L.-W. Xu, L. Li, Z.-H. Shi, Adv. Synth. Catal. 2010, 352, 243-279.
[4] Rahaman, H.; Madarasz, Á, Pápai, I.; Pihko. P. M. Angew. Chem. Int. Ed., accepted for publication.
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Diastereoselective and enantioselective tandem conjugate addition with Mannich reaction
Radovan Šebesta
Ferrocenyl diphosphanes, such as Josiphos and Taniaphos are efficient ligands for enantioselective addition of Grignard reagents to α,β-unsaturated carbonyl compounds.1 The reaction affords chiral substituted Mg-enolates, which react in a one-pot arrangement with N-benzylidene toluenesulfonamide to give β-aminocarbonyl compounds with three contiguous stereocenters. Two major diastereoisomers (d.r. 60:40) of product with enantioselectivities up to 95% ee were separated by flash chromatography.2 The choice of appropriate nitrogen protecting group on imine, together with conversion of Mg-enolate to silyl enol ether resulted in marked improvenment in diastereoselectivity (93:7) with high enantioselectivity (up to 96% ee).3
Fe
NMe2PPh2
Ph2P
O O
Me
Ph
HHN
P1. CuCl, TaniaphosMeMgBr2. TMSOTf
3.
NP
Ph
OPh
Ph
OPh
Ph
Chiral enolates, produced by Cu-taniaphos-catalyzed conjugate addition of RMgX to cyclic enones, react with aminomethylating reagent. The reaction is mediated by TICl4 and the resulting Cbz-protected aminomethyl ketones are obtained in high enantiomeric purities (d.r. 2:1, up to 93% ee).
[1] Lopez, F.; Minnaard, A. J.; Feringa, B. L. Acc. Chem. Res. 2007, 40, 179. [2] Enantioselective one-pot conjugate addition of Grignard reagents followed by Mannich reaction. Šebesta, R.; Bilčík, F.; Fodran, P. Eur. J. Org. Chem. 2010, 5666-5671. [3] Šebesta, R.; Galeštoková, Z. manuscript in preparation.
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Cinchona alkaloids – what they can do beside catalysis?
Karol Kacprzak Department of Chemistry, A. Mickiewcz University, Poznań, Poland;
[email protected] Cinchona alkaloids since long time have been considered as the attractive chiral catalysts for numerous organic reactions carried out in an enantioselective fashion [1]. However the eruption of highly enantioselective catalysis promoted by Cinchona alkaloids and their derivatives which has been observed in only last two decades allowed them to be recognized as “privileged catalysts” [2]. Contrary, beside their use in catalysis, these highly functionalized molecules have only hardly been used in the construction of chiral discrimination and separation systems. Efforts in this field (Figure) including design of the molecular switch [3], an indicator displacement assay for tartrates [4], chirality sensors and Cinchona alkaloid-based chiral stationary phases for enantioselective chromatography [5] will be presented.
[1] a) K. Kacprzak, J. Gawroński, Synthesis 2001, 961-999; b) Cinchona Alkaloids in Synthesis&Catalysis, Ch. E. Song
(Ed.) Wiley-VCH Weinheim 2009. [2] prix [3] a) K. Kacprzak, J. Gawroński, Chem. Commun. 2003, 1532-1533; b) J. Gawroński, K. Gawrońska, K. Kacprzak,
Chirality, 2001, 13, 322-328. [4] K. Kacprzak, J. Grajewski, J. Gawroński, Tetrahedron: Asymm., 2006, 17, 1332-1336. [5] a) K. M. Kacprzak, N. M. Maier, W. Lindner, J. Chrom. A, 2011, 1218, 1452-1460; b) K. Kacprzak, N. Maier, W.
Lindner J. Sep. Sci., 2010, 33, 2590–2598; c) K. M. Kacprzak, N. M. Maier, W. Lindner Tetrahedron Lett., 2006, 47, 8721-8726.
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Evaluation of Strategies for the Step-Efficient Assembly of Densely Functionalized Molecules
Prof. Dr. Mathias Christmann
TU Dortmund, Otto-Hahn-Str. 6, 44227 Dortmund Our group’s target-oriented synthesis program is focussed on the synthesis of biologically relevant natural products. In particular, we have contributed to the deployment of organocatalytic reactions in total synthesis [1] Using novel modes of activating organic substrates, such as dienamine catalysis [2], has allowed for the discovery of highly efficient routes to complex molecules. We have applied this technology platform to access medicinally relevant scaffolds, such as nitrogen heterocycles. Most recently, we have synthesized the telomerase inhibitor UCS-1025A [3], the cytotoxic marine natural product amaminol B [4] and the guaiane sesquiterpene englerin A [5], a compound that exhibits very high selectivity against several renal cancer cell lines.
[1] E. Marqués-López, R. P. Herrera, M. Christmann, Nat. Prod. Rep. 2010, 27, 1138. [2] a) E. Marqués-López, R. P. Herrera, T. Marks, W. C. Jacobs, D. Könning, R. M. de Figueiredo, M. Christmann, Org. Lett. 2009, 11, 4116; b) R. M. de Figueiredo, R. Fröhlich, M. Christmann, Angew. Chem. Int. Ed. 2008, 47,
1450; c) Stiller, E. Marqués-López, R. P. Herrera, R. Fröhlich, C. Strohmann, M. Christmann Org. Lett. 2011, 13, 71.
[3] R. M. de Figueiredo, R. Fröhlich, M. Christmann, Angew. Chem. Int. Ed. 2007, 46, 2883. [4] W. C. Jacobs, M.Christmann, Synlett 2008, 247. [5] a) M. Willot, L. Radtke, D. Könning, R. Fröhlich, V. H. Gessner, C. Strohmann, M. Christmann, Angew. Chem. Int. Ed. 2009, 48, 9105; b) M. Willot, M. Christmann Nature Chem. 2010, 2, 519; c) L. Radtke, M. Willot, H. Sun, S. Ziegler, S. Sauerland, C. Strohmann, R. Fröhlich, P. Habenberger, H. Waldmann, M. Christmann, Angew. Chem. Int. Ed. 2011, 50, DOI: 10.1002/anie.201007790.
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New Dimension of Chiral Acid and Base Catalysis
Shū Kobayashi Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku,
Tokyo 113-0033 Japan. Email: [email protected]; Fax: +81-3-5684-0634
Recently we have developed alkaline earth metal catalysts. Catalytic asymmetric 1,4-addition and [3+2] cycloaddition reactions using chiral calcium complexes prepared from calcium isopropoxide and chiral bisoxazoline ligands have been developed. Glycine Schiff bases reacted with acrylic esters to afford 1,4-addition products, glutamic acid derivatives, in high yields with high enantioselectivities. During the investigation of the 1,4-addition reactions, we unexpectedly found that a [3+2] cycloaddition occurred in the reactions with crotonate derivatives affording substituted pyrrolidine derivatives in high yields with high enantioselectivities. Based on this finding, we investigated asymmetric [3+2] cycloadditions, and it was revealed that several kinds of optically active substituted pyrrolidine derivatives containing contiguous stereogenic tertiary and quaternary carbon centers were obtained with high diastereo- and enantioselectivities. NMR spectroscopic analysis and observation of non-amplification of enantioselectivity in non-linear effect experiments suggested that a monomeric calcium complex with an anionic ligand was formed. A stepwise mechanism of the [3+2] cycloaddition, consisting of 1,4-addition and successive intramolecular Mannich-type reaction was suggested. Furthermore, modification of the Schiff base structure resulted in a modification of the reaction course from a [3+2] cycloaddition to a 1,4-addition affording 3-substituted glutamic acid derivatives with high diasterero- and enantioselectivities. Furthermore, the idea and the concept of “Catalytic Carbanion Reaction,” silver amide-catalyzed reactions, and fluorenone imines for C-C bond formation will be discussed.
O
OR1N
R3
R2
R4
O
R7R5
R6
+NH
R5R7O
O
OR1N
R3
R2
R7 O
R6R5
R3 R4R2
OR1
OH
H Chiral CaCatalyst
up to quantup to >99/1 dr
up to >99% ee (major)
up to quantup to >99/1 dr
up to 99% ee (major)
Chiral Ca Catalyst
[1] S. Kobayashi, Y. Yamashita, Acc. Chem. Res. 2011, 44, 58. [2] Y. Yamashita, T. Imaizumi, S. Kobayashi, Angew. Chem. Int. Ed. in press. [3] T. Poisson, Y. Yamashita, S. Kobayashi, J. Am. Chem. Soc. 2010, 132, 7890. [4] T. Tsubogo, Y. Yamashita, S. Kobayashi, Angew. Chem. Int. Ed. 2009, 48, 9117. [5] S. Kobayashi, R. Matsubara, Chem. Eur. J. 2009, 15, 10694.
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Poster Session
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Development of cinchona alkaloids in direct asymmetric aldol reaction of hydroxyketones
Sebastian Baś,a Judyta Cygan,a Jacek Mlynarski* a,b
aFaculty of Chemistry, Jagiellonian University Ingardena 3, Krakow, Poland
bInstitute of Organic Chemistry, Polish Academy of Sciences Kasprzaka 44/52, Warsaw, Poland
[email protected], www.jacekmlynarski.pl
The cinchona alkaloids and they derivatives played important role in modern organic synthesis.[1] Recently we showed a new application of cinchona alkaloids as organocatalyst in direct asymmetric aldol reaction of aromatic hydroxyketones and aliphatic aldehydes.[2] Aldol reaction between these reagent belong to the most troublesome examples. Only a few papers have been published on asymmetric aldol reaction of such hydroxyketones, all with metal complexes as catalyst.[3]
Our results show that cinchona alkaloids are efficient organocatalyst in asymmetric aldol reaction of hydroxyketones. Desired diols have been obtained with good yield, high syn-diasteroselectivity and moderate enantiomeric excess.
Application of both cinchonine and cinchonidine alkaloids in diastereoselective reaction of glyceraldehyde gave access to de novo synthesis of hexulosonic acid – common component of bacterial lipopolysacharides (LPS).
[1] T. Marcellim, H. Hiemstra, Synthesis, 2010, 8, 1229-1279. [2] J. Paradowska, M. Rogozińska, J. Mlynarski, Tetrahedron Lett., 2009, 50, 1639-1641. [3] (a) B. M. Trost, H. Ito, E. R. Silcoff, J. Am. Chem. Soc., 2001, 123, 3367-3368. (b) N. Yoshikawa, T. Suzuki, M.
Shibasaki, J. Org. Chem, 2002, 67, 2556-2565.
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Stereochemistry control in glycosylation via modified O-2-benzyl group
Szymon Buda,a Patrycja Gołębiowska,a Jacek Mlynarski* a,b aFaculty of Chemistry Jagiellonian University
Ingardena 3, Krakow, Poland; bInstiytute of Organic Chemistry, Polish Academy of Sciences,
Kasprzaka 44/52, Warsaw, Poland [email protected], www.jacekmlynarski.pl
Stereocontrolled synthesis of a new glycosidic bond is one of the most interesting and most investigated issues in organic chemistry. This problem can be solved in many ways. One of the methods can be use of appropriate protecting groups which as a result of anticipated impact enforced proper conformation or allow to obtain the desired electronic structure. One of the most versatile methodology is the use of adjunctive ester-type group at O-2 position of monosaccharide ring. Venturing into the synthesis of complex molecules we often do not have the possibility to introduce desired ester group in specified position. An interesting solution is the use of the 2’-pirydylmethyl group activating the anomeric center by forming six-membered ring.1 The advantage of the application of 2-O-picolyl group beside of stabilization of the intermediate product leading to β-glycoside, is its stability comparable to the ether groups.
Figure 1. Stereochemistry control in glycosylation
Presented strategy will be presented in glycosydation of monosaccharides as well as in the synthesis of complex polysaccharide motives.
[1] (a) J. T. Smoot, P. Pornsuriyasak, A. V. Demchenko, Angew. Chem. Int. Ed,. 2005, 44, 7123-7126; (b) J. T. Smoot,A.
V. Demchenko, Org. Chem. 2008, 73, 8838-8850.
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Stereoselective synthesis of long-chain carbohydrates
Maciej Cieplak, Sławomir Jarosz*
Institute of Organic Chemistry PAS ul. M. Kasprzaka 44/52, 01-224 Warsaw
Monosaccharides, containing more than 10 carbon atoms in the chain, higher carbon sugars, has interesting properties, although only few of them can be found in nature. They can be used as non-metabolized analogues of di- and oligosaccharides. They are interesting targets for developing new synthetic methodologies and studying the conformational features. Only limited examples of the synthesis of such derivatives are reported in the literature. In the past several years we have elaborated a convenient methodology for the preparation of higher dialdoses by coupling of two suitably activated simple sugar subunits. Especially useful was the reaction of phosphonates with sugar aldehydes providing a higher enone, finally converted into the desired dialdose. The key-step in the synthesis was the functionalization of the three-carbon atom bridge connecting two carbohydrate subunits.[1]
We have demonstrated the stereoselective synthesis of long-chain carbohydrates in which protective groups could be cleveladged in the selective way. However, further selective functionalization of this higher carbohydrate was not possible. Also introducing of functional groups sensitive to reducting, oxydasing nor basic environment in starting material was not possible.
OO
O
O
DAGA
O
OO
O
O
O
O
OOO
O CMe2
Me2C
O P
OOMeOMe
O O
OBnO BnO
BnO
OO
OO
O
OO O
OBnO BnO
BnO
OO
OO
O+
functionalization
selective hydrolysis
DAGA
1
12
1
12
Fig. 1. Synthesis of higher carbon sugars with 'deprotected end'
1. Zn(BH4)2
2. BnBr, NaH3. OsO4, NMO4. BnCl, TEBACl, NaOH(50% aq.)
1 11
We have decided to use the methodology proposed by Enders and Barbas III. They have combined aldehydes with protected dihydroxyacetone by direct aldol condensation promoted by (S)-proline.[2] This methodology allowed us to connect carbohydrate aldehyde with 2,2-dimethyldioxan-5-one. It opens a route to join two carbohydrate sub-units via three carbon dihydroxyacetone bridge under mild conditions.
OO
O
O
OO
O
O
O
OH
O O
O
O O
O
sug1O
OH
O O
O
sug1
OH
sug2
O O
O
+ (S)-proline
Fig. 2a Synthesis of higher carbon (C-8) sugar catalyzed by (S)-proline
+1) (S)-proline
Fig. 2b Synthesis of higher carbon sugars by conecting of two carbohydrate sub-units via dihydoxyacetone three carbon bridge
2) Sug2-CHO (S)-proline
[1] S. Jarosz, J. Carbohydr. Chem., 2001, 20, 93-107. [2] D. Enders, S.J. Ince, M. Bonnekessel, J. Runsik, G. Raabe, Synlett,, 2002, 962. J.T. Suri, S. Mitsumori, F. Tanaka, C.F. Barbas III, J. Org. Chem.,, 2006, 71, 3822-3828.
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Synthesis of Chiral Tertiary Diamines Derived from (L)-proline and their Application in Asymmetric Catalysis
Rafał Ćwiek, Zbigniew KałuŜa*
Institute of Organic Chemistry, Polish Academy of Sciences 01-224 Warszawa, Poland
Chiral tertiary diamines have been widely used as efficient chiral inductors in many asymmetric transformations.[1] This work presents synthesis of C2-symmetric diamines type 5 and spiro diamine 8, as well as their application in asymmetric catalysis. Methodology of the preparation of diamine 5 consist of the alkylation of (L)- proline derived Seebach’s oxazolidinone 1[2], DIBAL reduction of 2 followed by base hydrolysis to give amino aldehyde 3, which can be isolated as dimeric hemiaminal ether 4. (Scheme. 1). Finally, its reduction with sodium triacetoxyborohydride gives compound 5. Spiro diamine 8 was prepared via simple functionalization of enantiopure aminoketon 7. Synthesis of 7 was accomplished starting from the same Seebach’s oxazolidinone 1 via one pot reaction sequence: alkylation with o-bromobenzyl bromide followed by Parham[3] cyclization.
Scheme 1.
Obtained diamines 5 and 8 were successfully applied in asymmetric acylation of meso-diols and Henry reaction.
[1] J.-C. Kizirian, Chem. Rev. 2008, 108, 140-205.
[2] D. Seebach, M. Boes, R. Naef, W. B. Schweizer, J. Am. Chem. Soc. 1983, 105, 5390.
[3] W. E. Parham Acc. Chem. Res. 1982, 15, 300.
NHO
NO
O
Br
NO
O
1
1. t-BuLi2. o-bromo-benzyl-bromide
3. t-BuLi
6
5
62%
NN
R1
R2
7R2
R1,R2=alkyl
LDARX
NO
O
R
1. DIBAL
2. Na2CO3,H2O, MeCN
NH
O
RN
NO
R
R
NaBH(OAc)3
DCM
NN
R
R
24
R=Me, Bn3
8
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Organocatalytic Michael Reaction under High Pressure: Asymmetric Synthesis of
γ-Nitroketones with Quaternary Stereogenic Centers
Krzysztof Dudziński,a Piotr Kwiatkowski* a,b a Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw; bInstitute of Organic
Chemistry Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland [email protected], [email protected]
Development of new asymmetric organocatalytic methods and processes1 has become an important direction in modern stereoselective organic synthesis. Conjugate additions to α,β-unsaturated carbonyl compounds belongs to the most important and versatile reactions, successfully carried out in organocatalytic manner.1 However, this type of asymmetric transformations is practically restricted to β-mono-substituted Michael acceptors. We focused our attention on reactions of prochiral β,β-disubstituted enones with various carbon nucleophiles, leading to products containing quaternary stereogenic centers. Until now β,β-disubstituted cyclic enones were successfully employed in organocatalytic hydrogenation2 and epoxidation.3 1,4-Conjugate addition of nitroalkanes is also possible, however is limited to 3-n-alkylcyclohexenones and require long reaction time and 20 mol% of catalyst.4
In this communication we present examples of enantioselective conjugate addition of nitroalkanes to cyclic and selected acyclic enones, catalyzed by chiral primary-amines. We found that high pressure (ca.10 kbar) remarkably accelerate investigated reactions with low loading of catalyst and very high enantioselectivity. Acknowledgements: Many thanks to Professor Janusz Jurczak for his help and encouragement. Financial support from the Ministry of Science and Higher Education (grant no. N N204 145740) and Foundation for Polish Science are gratefully acknowledged. [1] P. I., Dalko, Ed. Enantioselective Organocatalysis, Wiley-VCH: Weinheim, 2007. [2] (a) J. B. Tuttle, S. G. Ouellet, D. W. C. MacMillan, J. Am. Chem. Soc. 2006, 128, 12662-12663; (b) N. J. A. Martin, B. List, J. Am. Chem. Soc. 2006, 128, 13368-13369. [3] X. Wang, C. M. Reisinger, B. List, J. Am. Chem. Soc. 2008, 130, 6070-6071. [4] (a) C. E. T. Mitchell, S. E. Brenner, S. V. Ley, Chem. Commun. 2005, 5346–5348. (b) P.Li, Y. Wang, X. Liang, J. Ye, Chem. Commun., 2008, 3302–3304.
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Biomimetic synthesis of bioactive 3-deoxy-ulosonic acid precursors
Osama El-Sepelgya, Piotr Oskwareka, Darius Schwarzera, Jacek Młynarski* a,b aFaculty of Chemistry, Jagiellonian University
Ingardena 3, Krakow, Poland bInstitute of Organic Chemistry Polish Academy of Sciences
Kasprzaka 44/52, Warsaw, Poland [email protected], [email protected]
The 3-deoxy-2-ulosonic acids are a diverse family of natural carbohydrates, participating in many important biological processes. For example, 3-deoxy-D-gluco-hex-2-ulosonic acid phosphate (KDGP) is a part of Doudoroff pathway. KDO is the key component of the outer membrane of the lipopolysaccharides of Gram-negative bacteria, playing a crucial role in immunospecificity.[1] Catalytic asymmetric reactions of pyruvate equivalent and chiral glyceraldehyde has initially been published by Enders in 2007 by using (R)- and (S)-proline organocatalysts.[2] Enders’ methodology suffers from several drawbacks which include high catalyst and ketone loading, long reaction time, competitive Mannich elimination and self condensation of ketone. Herein, we present the first successful example of asymmetric aldol reaction of pyruvate equivalents by mimicking of class II aldolases. Trost’s zinc-based[3] and Shibasaki’s lanthanum-lithium binol[4] catalysts were used to simultaneous activate donor and acceptor substrates. In conclusion, we have developed a direct entry to precursors of ulosonic acids by direct aldol reaction approach using metal complexes. Only 5 or 10 mol% of Trost’s or Shibasaki’s catalyst is sufficient to afford KDO or KDG precursors in good yields and stereocontrol from equimolar ratio of substrates. Importantly, Mannich elimination leading to undesired by-products could be avoided by using this protocol.
Figure 1. Biomimetic synthesis of bioactive 3-deoxy-ulosonic acid precursors
____________________
[1] A. Banaszek, J. Mlynarski, Stud. Nat. Prod. Chem.; (ELSEVIER B.V.) 2005, 30, 419. [2] D. Enders, T. Gasperi, Chem. Commun. 2007, 88-90. [3] B. M. Trost, H. Ito, J. Am. Chem. Soc. 2000, 122, 12003-12004. [4] N.Yoshikawa, N. Kumagai, S. Matsunaga, G. Moll, T. Ohshima T. Suzuki and M. Shibasaki, J. Am. Chem. Soc. 2001, 123, 2466-2467.
19 | P a g e
Effect of Pressure on the Organocatalytic Friedel-Crafts Reaction of Indoles with Enones
Dawid ŁyŜwaa, Piotr Kwiatkowski* a, b
aFaculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw bInstitute of Organic Chemistry Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw
[email protected], [email protected]
Asymmetric organocatalysis is a very attractive way to produce chiral molecules, however, in many reactions the limitations concern high loading of catalyst, long reaction time, and narrow substrate scope. Influence of pressure on organocatalytic reactions seems to be weakly explored area of asymmetric catalysis.1 In our opinion, combination of organocatalysts with high-pressure methodology can increase efficiency of some reactions, especially with Michael-type acceptors.
In this communication we demonstrate influence of high pressure (up to 10 kbar) on asymmetric organocatalytic Friedel-Crafts alkylation of indoles with α,β-unsaturated ketones, (eg. benzylideneacetone) in the presence of catalytic amount of chiral primary amines derived from cinchona alkaloids.2 The high-pressure reaction is efficient even with 1-2 mol% of catalyst.
We also found that very difficult reactions of indole with β,β-disubstituted enones, leading to products containing quaternary stereogenic centers, can be successfully performed under high pressure
conditions. Many thanks to Professor Janusz Jurczak for his help and encouragement. Financial support from the Ministry of Science and Higher Education (grant no. N N204 145740) and Foundation for Polish Science are gratefully acknowledged. [1] Van Eldik, R.; Klaerner, F. G. Eds. High Pressure Chemistry: Synthetic Mechanistic and Supercritical Applications, Wiley-VCH: Weinheim, 2002. [2] a) Melchiorre, P. and co-workers, Org. Lett., 2007, 9, 1403-1405. b) Chen, Y. C. and co-workers, Org. Biomol. Chem.
2007, 5, 816-821. c) For review, see: Terrasson, V.; de Figueiredo, M. V.; Campagne J. M., Eur. J. Org. Chem. 2010, 14, 2635-2655.
NH
Ph
Me
O
NH
Ph
Me
O+
2 mol% of chiral primaryamine + acid additive
10 kbar85% y and 86% ee
(1 bar - 10 % y)
NH N
H
Me
Ochiral primary amine
quaternarystereocenter
acid additive
10 kbar70% y and 85% ee
(1 bar - no product)
CO2MeMe
Me
OMeO2C
Me+
20 | P a g e
An Entry to Carbapenams via Asymmetric Kinugasa Reaction Involving Cyclic Nitrones and Terminal Acetylenes
Adam Mames, Bartłomiej Furman, Marek Chmielewski*
Institute of Organic Chemistry Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
The copper(I) mediated reaction of nitrones for terminal acetylenes, which is known as Kinugasa reaction, represents an attractive method of direct formation of the β-lactam ring.[1,2] This reaction can be performed in many ways including diastereo- and enantioselective versions. In most cases, as 1,3-dipoles, simple acyclic nitrones have been used.[3] Number of reactions involving cyclic ones is limited.
Herein, we present recent studies on Kinugasa reaction involving cyclic nitrones readily available from hydroxy acids or amino acids and terminal acetylenes either achiral or bearing a stereogenic center.[4]
All investigated reactions proceeded in good yield and with high diastereoselectivity providing an attractive entry to carbapenams of a potential biological activity.[5] The stereochemical pathway of the reaction and influence of geometry and substitutions in one or both reactants on direction and magnitude of asymmetric induction will be discussed. [1] (a) M. Kinugasa, S. Hashimoto, J. Chem. Soc., Chem. Commun. 1972, 466–467, (b) R. Pal, S. Ghosh, K. Chandra, A.
Basak, Synlett 2007, 2321–2330. [2] A. Brandi, S. Cicchi, F. Cordero, Chem. Rev. 2008, 108, 3988-4035. [3] (a) M. Miura, M. Enna, K. Okuro, M. Nomura, J. Org. Chem. 1995, 18, 4999–5004; (b) M. Lo, G. Fu, J. Am. Chem. Soc.
2002, 124, 4572–4573; (c) M.-C. Ye, J. Zhou, Y. Tang, J. Org. Chem. 2006, 71, 3576–3582. [4] (a) S. Stecko, A. Mames, B. Furman, M. Chmielewski, J. Org. Chem. 2008, 73, 7402-7404; (b) S. Stecko, A. Mames,
B. Furman, M. Chmielewski, J. Org. Chem. 2009, 74, 3094-3100; (c) A. Mames, S. Stecko, P. Mikołajczyk, M. Soluch, B. Furman, M. Chmielewski, J. Org. Chem. 2010, 75, 7580-7587.
[5] Chemistry and Biology of β-Lactam Antibiotics, M. Morin, M. Gorman, Eds., Wiley-VCH, New York, 1982.
21 | P a g e
N-Hydroxypropargylamines synthesis catalyzed by NHC copper (I) complexes on water
Michał Michalak*
Institute of Organic Chemistry, Polish Academy of Sciences Kasprzaka 44/52, 01-224 Warsaw
It’s well-established that copper (I) halides[1] and its complexes with phosphine[2] and oxazoline[3] act as mediators/catalyst in the 1,3-dipolar cycloaddtion between nitrones and terminal acetylenes forming β-lactams by the course cycloaddiotn/rearrangement sequence (Figure 1, path A).[1] In our studies aimed to develop highly active catalyst for the Kunigasa reaction,[4] we turned our attention to a newly discovered NHC copper (I) halides complexes. These complexes exhibit excellent activity in comparison to the copper (I) halides salt in the formation 1,2,3-triazole.[5] However, initial studies of the cycloaddition of tartaric acid derivative nitrone and phenyl acetylene with catalytic amount IPrCuI showed that N-hydroxy-propargyl amine derivative appeard to be the major product instead of the β-lactam (Figure 1, path B) giving an easy access to rare class of valuable building block. Screeing of the solvent indicated that the best yield were achieved applying water.
ON
R1
R2R3N
R1
R2O
R3
NR1
R2
OHN
O R1
R2R3CuX salt orCuX/ligand
R3
NHCCuX
NHO
OtBu
OtBuNO
OtBu
OtBu
5 mol% SIPrCuIPhCCH
water, rt, 16h
96%
HPh
Path A Path B
Figure 1.
Further studies revealed possible formation of N-hydroxy-propargyl amine “on water” between an electronically diverse acetylenes and serie of sugar-derived nitrones. In all of cases, the respective N-hydroxy-propargyl amines were obtained as single diastereisomer. The influence of the structure of NHC copper (I) halides complexes as well as electronic structure of terminal acetylene will be also presented.
[1] M. Kinugasa, S. Hashimoto, J. Chem. Soc., Chem. Commun. 1972, 466. [2] a) M. M. C. Lo, G. C. Fu, J. Am. Chem. Soc. 2002, 124, 4572; b) R. Shintani, G. C. Fu, Angew. Chem. Int. Ed. 2003,
42, 4082. [3] M.-C. Ye, J. Zhou, Y. Tang, J. Org. Chem. 2006, 71, 3576. [4] a) S. Stecko, A. Mames, B. Furman, M. Chmielewski, J. Org. Chem. 2008, 73, 7402; b) S. Stecko, A. Mames, B.
Furman, M. Chmielewski, J. Org. Chem. 2009, 74, 3094; c) A. Mames, S. Stecko, P. Mikołajczyk, M. Soluch, B. Furman, M. Chmielewski, J. Org. Chem. 2010, 75, 7580.
[5] a) S. Díez-González, A. Correa, L. Cavallo, S. P. Nolan, Chem. Eur. J. 2006, 12, 7558; b)S. Diez-Gonzalez, E. C. Escudero-Adan, J. Benet-Buchholz, E. D. Stevens, A. M. Z. Slawin, S. P. Nolan, Dalton Trans. 2010, 39, 7595.
22 | P a g e
Lithium – Halogen Exchange Initiated Intramolecular Aryllithium Additions to Dihydropyridones
Łukasz Mucha, Bartłomiej Furman
Institute of Organic Chemistry, Polish Academy of Sciences Kasprzaka 44/52, 01-224 Warsaw
We have discovered a new method of synthesis of benzoquinolizidines and related homologues based on the lithium – halogen exchange initiated conjugate addition of aryllithium to dihydropyridones (Scheme 1).
Br
N
O
Rn
t -BuLi
THF
n=1,2
N
N
n
O
H
RO
R
HH
H
Scheme 1.
The mechanism suggests that the enolate intermediate is protonated on the top face (axial addition). When we made a tandem reaction with the enolate trapped by a different electrophile (BnBr), the product is also that of axial attact, while the reaction with aldehydes to give the corresponding enones (Scheme 2).
Br
N
O
R
1) t-BuLi
2) BnBr N
O
HPh
N
O
HR
1) t -BuLi
2) RCHO
Scheme 2.
23 | P a g e
Asymmetric Trifluoromethylation of α-Iminoketones Derived from Arylglyoxals
Emilia Obijalska, Alice Six†, Grzegorz Mlostoń* Department of Organic and Applied Chemistry, University of Lodz, Tamka 12, 91-403 Lodz
e-mail: [email protected], [email protected]
Synthesis of fluorinated compounds is an attractive topic in the modern organic synthesis.[1] Special interest is focused on derivatives containing trifluoromethyl moiety because of their potential applications.[1] One of the most popular reagents applied for incorporation of CF3 group into organic molecules is (trifluoromethyl)trimethylsilane (Ruppert’s reagent, CF3SiMe3, RR).[2] The aim of present study was the elaboration of an attractive, enantioselective method for preparation β-amino-α-(trifluoromethyl)alcohols which are known as useful building blocks for synthesis of fluorinated organic compounds. To the best of our knowledge, only one procedure for enantioselective synthesis of this compounds class of compounds, based on asymmetric Henry reaction, is described.[3] In our preliminary studies we developed a simple method for synthesis of racemic β-amino-α-(trifluoromethyl) alcohols of type 3 starting with α-iminoketones 1 derived from arylglyoxals.[4] In crucial step, the chemoselective addition of CF3SiMe3 to the C=O, followed by simultaneous reduction of C=N bond and desillylation, is performed. Some successful attempts of enantioselective reactions of Ruppert’s reagents with simple aldehydes and ketones are already reported.[5]
Addition reactions of RR with 1 were carried out in the presence of catalytic system (8R,9S)- or (8S,9R)-4/KF and they led chemoselectively to trimethylsillylethers 2. The latter compounds were converted into final products 3 in high overall yields (80-90%). However, the observed ee values remained low to moderate (< 60%). The ee values were determined based on the 1H or 19F NMR spectra registered for products 3 in the presence of (R)-mandelic acid or (R)-t-butyl-phenylthiophosphinic acid used as chiral solvating agents: ------------------------------------------------------
† On leave (April-July, 2011) from École Nationale Supérieure D’Ingénieurs de Caen (France). [1] (a) Kirsh, Modern Fluoroorganic Chemistry, Wiley-VCH, Weinheim, 2004; (b) J.-P. Bégué, D. Bonnet-Delpon,
Bioorganic and Medicinal Chemistry of Fluorine, Wiley, Hoboken, New Jersey, 2008. [2] G. K. S. Prakash, M. Mandal, J. Fluorine Chem., 2001, 112, 123. [3] F. Tur, J. M. Saá, Org. Lett., 2007, 9, 5079. [4] G. Mlostoń, E. Obijalska, A. Tafelska-Kaczmarek, M. Zaidlewicz, Journal of Fluorine Chem., 2010, 131, 1289. [5] (a) S. Mizuta, N. Shibata, M. Hibino, S. Nagano, S. Nakamura, T. Toru, Tetrahedron 2007, 63, 8521; (b) S. Mizuta, N.
Shibata, S. Akiti, H. Fujimoto, Org. Lett. 2007, 9, 3707; (c) X. Hu, J. Wang, W. Li, L. Lin, X. Liu, X. Feng, Tetrahedron Lett. 2009, 50, 4378.
Ar
NRO
NRF3C
Ar NR
OH
ArF3C
N
OH
N Ar
R
N
N
OH
R
Ar
CF3SiMe3 NaBH4H
1 2 3
Me3SiO
2 **
+Br
(8S,9R)-4-
+
Br -
(8R,9S)-4kat.*:
kat.*/F- 1
1
1
2
2
24 | P a g e
An application of aliphatic nitrones in Kinugasa reaction
Kamil Parda, Bartłomiej Furman, Marek Chmielewski* Institute of Organic Chemistry, Polish Academy of Sciences
Kasprzaka 44/52, 01-224 Warsaw [email protected]
The copper(I) mediated reaction of nitrones and terminal acetylenes, which is known as Kinugasa reaction, represents an attractive method of direct formation of the β-lactam ring.[1] This reaction can be performed in many ways including diastereo- and enantioselective versions.[2] In most known examples of Kinugasa cascade simple C,N-diaryl nitrones were applied. Recently, we have demonstrated that also aliphatic cyclic nitrones, particularly those derived from sugars, are also attractive substrates.[3] Presented approach opens an access to the bicyclic β-lactamic derivatives, for instance carbapenams and carbacephams, with interesting synthetic and biologic features.
Herein, we present our recent results on our ongoing studies on Kinugasa reaction involving aliphatic nitrones and terminal acetylenes. In particularly, we have focused our attention on nitrones and acetylenes derived from glyceraldehyde, malic acid or sugars. Presented results are the first cases of direct formation of monobactams via Kinugasa reactions starting from aliphatic nitrones. Investigated reactions proceeded with yield (65-80%) in the presence of catalytic amount of copper catalyst (up to 5 mol%). [1] (a) M. Kinugasa, S. Hashimoto, J. Chem. Soc., Chem. Commun. 1972, 466; (b) R. Pal, S. Ghosh, K. Chandra, A.
Basak, Synlett 2007, 2321. [2] J. Marco-Contelles, Angew. Chem. Int. Ed. 2004, 43, 2198. [3] (a) Mames, A.; Stecko, S.; Mikołajczyk, P.; Soluch, M.; Furman, B.; Chmielewski, M. J. Org. Chem. 2010, 75, 7580; (b)
Stecko, S.; Mames, A.; Furman, B.; Chmielewski, M J. Org. Chem. 2009, 74, 3094; (c) Stecko, S.; Mames, A.; Furman, B.; Chmielewski, M. J. Org. Chem. 2008, 73, 7402.
NR3O
R2OOR1
NOR3
OR2
OR1
R1OOR2
+
R1O OR2CuI (up to 5 mol%)
base
25 | P a g e
Organocatalytic aldol reaction – new method of synthesis iminosugars
Monika Pasternaka, Roman Plutaa, Jacek Młynarski*a,b
aFaculty of Chemistry, Jagiellonian University Ingardena 3, Krakow, Poland
bInstitute of Organic Chemistry, Polish Academy of Science Kasprzaka 44/52, Warsaw, Poland
[email protected], www.jacekmlynarski.pl
Iminosugars are monosacharide analogs in which the ring oxygen has been replaced by an imino group. Such iminosugars inhibit the glycosidases involved in a wide range of important biological processes because of their structural resemblance to the sugar moiety of the natural substrate and the presence of the nitrogen atom mimicking the positive charge of the glycosyl cation intermediate in the enzyme-catalyzed glycoside hydrolysis. Coumpouds from this group have potentially therapeutic applications include use in treatment of diabetes, cancer, AIDS, viral infections and metabolic disorders.[1,2]
Aldol reaction is one of the most useful method of stereoselective formation new carboncarbon bond. Now, when the researches of organocatalytic aldol reaction reached high level of sophistication, we could try to use whese methodology to the synthesis more complex molecules. The synthesis of iminosugars will be presented by using direct activation of hydroxyacetone and dihydroxyacetone donors. In these procedure we generate new stereogenic centres, which configurations was control by using chiral organocatalysts. We tested several popular aminoacid and chiral amine like catalyst in these reaction. [1] P. Compain, O. R. Martin, Iminosugars: From Synthesis to Therapeutic Applications; John Wiley & Sons Ltd.: Chichester, UK, 2007. [2] N. Palyam, M. Majewski, J. Org. Chem. 2009, 74, 4390-4392.
N
OH
OHHO
Ac
R
organocatalyst
stereochemistry depends oncatalyst structure
O
OH ON
H
O
Cbz+
26 | P a g e
OH
OR
CH3
CH3N
S
CH3
H3C
O
O
F
OH O
PPh3 , DIAD
O
OR
CH3
CH3N
S
CH3
H3C
O
O
F
OH O
R'O
OH
CH3
CH3N
S
CH3
H3C
O
O
F
O
O
PPh3 , DIAD
retention
inversion
R = H
R = CH3
OH
OH
CH3
CH3N
S
CH3
H3C
O
O
F
OH O
aq. NaOH
MeOH
ROSUVASTATIN
aq. NaOH
MeOH
The Mitsunobu reactions in sterically hindered molecular systems
Agnieszka Pazik, Anna Skwierawska* Department of Chemical Technology, Gdansk University of Technology
G. Narutowicza Street 11/12, 80-233 Gdańsk [email protected]
The Mitsunobu reaction is a unique dehydration-condensation reaction between alcohols and various nucleophiles using the redox system comprised of diethyl azodicarboxylate and trialkyl- or triarylphosphine.1 The reaction between secondary alcohols and nucleophiles yields products with Walden inversion unless sterically very congested. In this paper, we report that the intramolecular Mitsunobu reaction of rosuvastatine occurred with retention of configuration while intermolecular effected with inversion. In most instances, retention of configuration has been attributed to gross deviations in the intended mechanistic pathway involving SN2 or SN1 processes during the Mitsunobu reaction of allylic alcohols or neighboring group participation. These remarkable results provided insight into the mechanism of the Mitsunobu reaction. As anticipated from the accepted mechanism of the Mitsunobu reaction, hydroxyacid underwent stereospecific lactonization with retention of configuration to provide lactone. Hydrolysis of lactone with NaOH, followed by acidification gave hydroxyacids (Scheme 1).
Scheme 1. Inversion / retention of allylic alcool configuration by Mitsunobu reaction Since literature reveals that both the carboxylic acid and solvent used for the Mitsunobu inversion process exert a considerable influence on the outcome of the reaction, we performed either the Mitsunobu inversion of methyl (7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)-pyrimidin-5-yl]-(3R,5S)-dihydroxy-(E)-6-heptenate with various carboxylic acids in three different solvents: methylene chloride, tetrahydrofuran and toluene. The best result was achieved with chloroacetic acid. Probably as important as acid strength is acid molecule size. Among the solvents, only toluene proved convenient. [1] K. C. Kumara Swamy, N. N. Bhuvan Kumar, E. Balaraman, K. V. P. Pavan Kumar, Chem. Rev., 2009, 109, 2551-2651.
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Microwave-Assisted Ruthenium Catalysed Olefin Metathesisin Fluorinated Aromatic Hydrocarbons: a Beneficial Combination
Cezary Samojłowicz,a Etienne Borré,b,c Marc Mauduit,b,c,* and Karol Grelaa,d,*
aInstitute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland b”Sciences Chimiques de Rennes” UMR 6226 CNRS – Equipe Chimie Organique et
Supramoléculaire - Ecole Nationale Supérieure de Chimie de Rennes, Av. du Général Leclerc, CS 50837 - 35708 Rennes cedex 7, France, cUniversité européenne de Bretagne, Rennes, France,
dFaculty of Chemistry, Warsaw University, ul. Pasteura 1, 02-093 Warszawa, Poland, e-mail: [email protected]
http://karolgrela.eu/
High yield in ruthenium-based olefin metathesis of demanding substrates are commonly forced by using a high loading of a catalyst and conducting reactions at elevated temperature for extended time.[1] However, in many cases this approach is not fully effective. Herewith, we are going to present fluorinated aromatic hydrocarbons (FAH)[2-3] combined with microwave (MW) irradiation using commercially available 2nd generation ruthenium-based pre-catalyst[4] creates an attractive reaction conditions for promoting challenging olefin metathesis transformations.[5]
3 × 2 mol%
3 × 5 min 100 °C
Conditions (Solvent) Yield (%)
Thermal (C6F6)
0
29
RuCl
ClCy3P
NNPh
F
FF
F
F
catalyst
solventMicrowave (C6F6) 69
Thermal (C6H5CH3)NPh
O
ClNPh
O
Cl
F
During my presentation, application of FAH in synthesis of challenging molecules, including natural and biological active compounds will be given. Presentation will also provide an attempt to explain activation mechanism of metathesis transformation catalysed by 2nd generation ruthenium complexes in FAHs.[6] [1] M. Bieniek, A. Michrowska, D. L. Usanov, K. Grela, Chem. Eur. J. 2008, 14, 806; [2] R. Kadyrov, M. Bieniek, K. Grela, „Verfahren zur Metathese in electroarmen aromatischen Lösungsmitteln“, Pat. Appl., DE 102007018148.7, April 11 2007. [3] C. Samojłowicz, M. Bieniek, A. Zarecki, R. Kadyrov, K. Grela, Chem. Commun. 2008, 6282; [4] C. Samojłowicz, M. Bieniek, K. Grela, Chem. Rev. 2009, 109, 3708. [5] C. Samojłowicz, E. Borré, M. Mauduit, K. Grela, Adv. Synth. Catal. 2011, 353, DOI: 10.1002/adsc.201100053 [6] C. Samojłowicz, M. Bieniek, A. Pazio, A. Makal, K. Woźniak, A. Poater, L. Cavallo, J. Wójcik, K. Zdanowski, K. Grela, Chem. Eur. J. 2011, 17, DOI: 10.1002/chem.201100160 * CS thanks for financial support from the Foundation for Polish Science (“Ventures” Program).
28 | P a g e
New Chiral C2-symmetric Ligands with the Easily Accessible Dihydroanthracene Framework
Renata Siedlecka, Rafał Wal
Faculty of Chemistry, Organic Chemistry Department, Wrocław University of Technology, Wyb. Wyspiańskiego 27, 50-370 Wrocław, Poland,
e-mail: [email protected]
Many efforts have been made to design chiral auxiliaries and ligands useful for asymmetric induction.[1] Dihydroethanoanthracene derivatives, easily obtained in Diels-Alder reaction of anthracene with fumaric acid derivatives, are versatile organic molecules with C2-symmetry.They have been used in biological[2] and synthetic[3] applications. The latter include their use as chiral ligands in different enantioselective reactions.[4] Within our project we were looking for new chiral ligands of this type. Two approaches were applied in their synthesis. We functionalized the racemic framework with chiral reagent, expecting diastereomeric enrichment of the product. Alternatively we performed deracemisation of the dihydroanthracene subunit before functionalization.
COOHHOOC
OHHO
CHOOHC
NN
OO
RR
SPhPhS
NNAr
Ar HNNHPh
Ph
Figure 1. Experiments with catalytic application of the obtained chiral compounds are underway. [1] B. M. Trost, D. L. Van Vranken, C. Bingel, J. Am. Chem. Soc.1992, 114, 9327-9343; R. Annunziata, M. Benglia, M.
Cinquini, F. Cozzi, C. R. Woods, J. S. Siegel, Eur. J. Org. Chem. 2001, 173-180. [2] For example see: C. Santelli-Rouvier and all. , Eur. J. Med. Chem. 2003,38, 253-263. [3] K. L. Burgess, N. J. Lajkiewicz, A. Sanyal, W. Yan, J. K. Snyder, Org. Lett. 2005, 7, 31-34. [4] For recent applications see: S. A. Moteki, S. Xu, S. Arimitsu, K. Maruoka, J. Am. Chem. Soc. 2010, 132, 17074-17076;
Y. N. Belokon and all. Tetrahedron: Asymmetry, 2011, 22, 167-172.
29 | P a g e
The Copper(I) Mediated Reaction of Sugar-Derived Nitrones and Terminal Acetylenes - An Approach to the Synthesis of Carbapenams
Magdalena Soluch, Bartłomiej Furman, Marek Chmielewski* Institute of Organic Chemistry, Polish Academy of Sciences,
Kasprzaka 44/52, 01-224 Warsaw, Poland [email protected]
The copper(I)-mediated reaction between nitrones and terminal acetylenes, discovered in 1972 by Kinugasa and Hashimoto,[4] represents a direct and simple method of the β-lactam ring formation (Scheme 1). While the Kinugasa shown a great potential in 2-azetidinone synthesis,[5] there reaction has are only a few reports detailing the related diastereo-[6] and enantioselective protocols.[7]
Very recently, we reported a diastereoselective version of the Kinugasa reaction involving chiral cyclic nitrones, derived from malic and tartaric acids, and simple achiral or nonracemic acetylenes.[3c,d] The interesting preliminary results[3c,d] prompted us to further investigate the Kinugasa reactions involving both nonchiral or with a stereogenic center acetylenes and five-membered ring nitrones, derived from the simple, commercially available, carbohydrates (Scheme 2).
[1] (a) Kinugasa, M.; Hashimoto, S. J. Chem. Soc., Chem. Commun. 1972, 466. (b) Marco-Contelles, J. Angew. Chem.,
Int. Ed. 2004, 43, 2198. (c) Pal, R.; Ghosh, S.; Chandra, K.; Basak, A. Synlett 2007, 15, 2321. [2] (a) Ding, L. K.; Irwin, W. J. J. Chem. Soc., Perkin Trans. 1 1976, 2382. (b) Zhao, L.; Li, Ch.-J. Chem. Asian J. 2006, 1-
2, 203. [3] (a) Basak, A.; Gosh, S. C.; Bhowmick, T.; Das, A. K.; Bertolasi, V. Tetrahedron Lett. 2002, 43, 5499. (b) Zhang, X.;
Hsung, R. P.; Li, H.; Zhang, Y.; Johnson, W. L.; Figueroa, R. Org. Lett. 2008, 10, 3477. (c) Stecko, S.; Mames, A.; Furman, B.; Chmielewski, M. J. Org. Chem. 2008, 73, 7402.
[4][ (a) Lo, M.; Fu, G. C. J. Am. Chem. Soc. 2002, 124, 4572. (b) Shintani, R.; Fu, G. C. Angew. Chem., Int. Ed. 2003, 42, 4082. (c) Ye, M.-C.; Zhou, J.; Tang, Y. J. Org. Chem. 2006, 71, 3576.
R3NR2
R1
O+
NO
R3 R2
R1
Cu(I), base
Scheme 1
N OBn
OBn
O
sugarsR
N
R
O
OBn
OBn
HH
12 h
CuI
Scheme 2
30 | P a g e
Cyclic Imine Sugars – building blocks in the asymmetric synthesis of indolizidines
Piotr Szcześniak, Bartłomiej Furman* Institute of Organic Chemistry, Polish Academy of Sciences
Kasprzaka 44/52, 01-224 Warsaw, Poland
The synthetic application of carbohydrates in a stereocontrolled organic synthesis has to be considered in context of at least two aspects. Sugars can be employed as starting materials in the target-oriented synthesis (a chiral pool synthetic approach) or, due to their enantiomeric purity, they can serve as stereodifferentiation agents in the formation of a new stereogenic center (a chiral auxiliary approach)1. During the presentation we will present the use of sugar derived cyclic imines as building blocks in the synthesis indolizidine alkaloids (figure 1).
Figure 1.
[1] Stephen F. Martin, Pure Appl. Chem., 2009, 81, 195-204
TMSO OMe
Lewis acid
NTBSO
TBSO
N
BnO
BnO
BnO
NBnO
BnO
natural polihydroxylated indolizidines
N
H
OH
OH
N
H OHlentiginosine OH
HO
HO
castanospermine
N
H OHOH
swainsonine
OH
sugar-derived imines tested
NOTBS
OTBSO
H
yield 54%, de. 89%
N
OBnO
OBn
OBn
yield 55%, de. 66%
NOBn
O
OBn
yield 55%, de. 34%
H
H
31 | P a g e
Acid Catalyst 1,3-Dipolar Cycloaddition Reactions of Sugar Derived Lactones with Diaryl Nitrones
Marcin ŚnieŜek, Bartłomiej Furman, Marek Chmielewski*
Institute of Organic Chemistry, Polish Academy of Scienses Kasprzaka 44/52, 01-224 Warsaw
[email protected] The 1,3-dipolar cycloaddition reactions are the powerful tool in the synthesis of five-membered heterocycles. These reactions proceed via concerted suprafacial mechanism which ensures the complete stereochemical information transfer from substrates to the products. With these reactions, up to four stereogenic centers can be created in a single step.1 Stereodifferentiating groups can be introduced either in the 1,3-dipole or in the dipolarophile. Two synthetic methods leading to non-racemic izoxazolidines are discussed. One involves thermally induced 1,3-dipolar cycloaddition of sugar derived lactones with diaryl nitrones. The second one involves the scandium triflate catalyzed reaction.
The second method seems to be most advantageous since it allows synthesis of izoxazolidines with high asymmetric induction. This methodology has been successfully applied to the synthesis of chiral β-lactams. [1] A. Padwa, W. H. Pearson, “Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products”, John Wiley & Sons, Inc., New York, 2002
SUGARS
O O
HO
OOAcO
OAc
OAc
OAc
AcO
O
OMe
O
O
HO
ON
Ar
Ar
O
O
OAc
AcON
O
Ar
Ar
OAc
OAc
AcO
OO
O NAr
Ar
N+
-O
ArArB-Lactams
TermalorSc(OTf)3
32 | P a g e
Synthesis of 2-vinyl pyrrolidines and piperidines via Overmann rearrangement/cyclization sequence
Sebastian Stecko,* Przemysław Taciak
Institute of Organic Chemistry, Polish Academy of Sciences Kasprzaka 44/52, 01-224 Warsaw
Sigmatropic rearrangements of allylic systems have fund wide application in organic synthesis, with carbon-carbon bond forming rearrangement such as the Cope and Claisen rearrangement being particularly well known. The sigmatropic rearrangement of allylic imidates (also known as the aza-Claisen or Overman rearrangement) offers a valuable entry into the preparation of protected allylic amines which are important and valuable building blocks for organic synthesis.[1]
Aim of these research is to combine Overnam rearrangement of allylic imidates with cyclization process of resulting allyl amines to provide 2-vinyl heterocycles, for instance pyrrolidines or piperidines, which are important precursors of numerous bioactive compounds. Although several tandem processes involving Overman rearrangement have been reported,[2] the rearrangement/cyclization sequence (as a tandem or one-pot procedure) was not demonstrated so far. [1] L.E. Overman, N.E. Carpenter Org. React. 2005, 66, 1. [2] (a) O.V. Singh, H. Han, Org. Lett. 2004, 6, 3067; (b) M.D. Swift, A. Sutherland Org. Lett. 2007, 9, 5239.
NHO
CCl3
NH∗
O
LG
CCl3
Overmanrear rangemnet ∗∗
N
TCA
cyclizat ionLG
R(H) R(H) R(H)alkaloidsiminosugarslactams
one-pot or tandem process
33 | P a g e
Regioselective Mukaiyama reaction of TMS-furan in aqueous media
Marta Woyciechowskaa, Jacek Mlynarski*a,b aFaculty of Chemistry, Jagiellonian University
Ingardena 3, Krakow, Poland bInstitute of Organic Chemistry, Polish Academy of Science
Kasprzaka 44/52, Warsaw, Poland [email protected]
Siloxy furans are versatile and commonly used carbon nucleophiles.[1] Here, we present results of our investigation of stereoselective Mukaiyama reaction in the presence of water. We noticed suprising and solvent-dependent regioselectivity in the investigated reaction when catalyzed by Lewis acids.
Figure 1. Regioselective Mukaiyama reaction of TMS-furan in aqueous media.
According to the literature,[2] application of dry solvents results the product of the vinylogous Mukaiyama reaction. In the case of mixtures of water and organic solvents, we observed the formation of Mukaiyama product, predominantly. That product is the γ-lactone derivative resulting from carbon-carbon bond formation at C3 position of TMS-furan, followed by double bond isomerization. Product of the vinylogous Mukaiyama reaction was observed as the side product (yield up to 15%). The hydrolysis of the TMS-furan to ketone was possible, so the reaction of 2(5H)-furanon and benzaldehyde was invstigated both in dry solvents and in the aqueous media. In all studied cases Morita-Baylis-Hillman reaction did not occur. Moreover, Mukaiyama reaction of siloxy furans with other aldehydes (aromatic, aliphatic, unsaturated) has been investigated. Moreover, our further studies focuses on the application of chiral metal complexes. This reaction seems also promising for the further extension. [1] G. Casiraghi, F. Zanardi, G. Rassu, P. Spanu, Chem. Rev. 1995, 95, 1677. [2] T. Ollevier, J. Bouchard, V. Desyroy, J. Org. Chem. 2008, 73, 331.
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New, optically active ionic liquids prepared from enantiomerically pure [1-((S)-pyrrolidin-2-yl)methyl]imidazoles
Aneta Wróblewska, Grzegorz Mlostoń* Department of Organic and Applied Chemistry, University of Łódź
ul. Tamka 12, 91-403 Łódź [email protected]; [email protected]
(S)-Proline belongs to the group of natural amino acids and is commonly used as an inexpensive and readily available organocatalyst in many reactions.[1] On the other hand, there is an increasing interest in the chemistry of diverse imidazole derivatives, which can be used inter alia in the synthesis of quaternary salts, most of which indicate the properties of ionic liquids. Reactions of the primary amine (S)-1[2] with paraformaledehyde and appropriate α-hydroxyiminoketones led to imidazole N-oxides (S)-2, containing pyrrolidine ring according to literature procedure[3]. These compounds were converted into a series of imidazolium salts (S)-3, which display properties of ionic liquids at room temperature (RTIL).
Scheme 1. The sequence of transformations leading to quaternary imidazolium salts.
One of the enantiomerically pure ionic liquids of type (S)-3 was selected as a solvent used in 1,3-dipolar cycloaddition reactions of the azomethine ylide 5 with aromatic thioketones 6. It was found that the stereochemical course of the 1,3-thiazolidine 7 formation differs dramatically from that observed in a nonpolar solvent (toluene).
Scheme 2. The 1,3-dipolar cycloaddition reactions between an azomethine ylide 5 with aromatic thioketones 6.
[1] (a) B. List, Tetrahedron, 2002, 58, 5573-5590; (b) P. I. Dalko, L. Moisan, Angew. Chem., Int. Ed. 2004, 43, 5138-5175. [2] M. T. Rispens, O. J. Gelling, A. H. M. De Vries, A. Meetsma, F. Van Bolhuis, B. L. Feringa, Tetrahedron, 1996, 52,
3521-3546. [3] M. Jasiński, G. Mlostoń, P. Mucha, A. Linden, H. Heimgartner, Helv. Chim. Acta, 2007, 90, 1765-1780.
N
Bn
N
N
O
R
R 1
2
+
N
Bn
NH2
N
Bn
N
NR
R
X(CH2)-BF4
(S)-1 (S)-2 (S)-3
1
2
+
nCH3
X = CH2 or OCH2
N
S
Me
PhPh
R
R
N
S
Me
PhPh
R
R
N
Me
Ph
Ph+
..-
N
Me
PhPh+
..-ionic liquid
110oC, 24h
R2C=S
6
NH H
Me
PhPh
cis-4 (E,Z)-5 (E,E)-5 cis-7 trans-7
+