Novel sulfur containing electrophiles in asymmetric organocatalysis

Three different kinds of sulfur containing electrophiles in organo- and metal catalyzed reactions have been evaluated. We demonstrated the first diastereoselective reaction of beta-keto esters with 1-chloroethylphenyl sulfide catalyzed by cinchona alkaloids. At the same time, we could confirm the high substrate specificity of the reactions with alpha-chlorosulfides. The conditions optimized for methyl-2-cyclopentanonecarboxylate allowed us to perform reactions only with the very similar 2-acetylbutyrolactone. It has been shown that diastereo- and enantioselective reactions with this class of electrophiles are possible. They involve a dual catalytic cycle. In both cases moderate to very good yields and diastereoselectivities were obtained. However, the design of a general method for wide substrate scope was unsuccessful. Due to their liability, alpha-chlorosulfides are problematic electrophiles for use in Lewis acid- and organocatalyzed reactions. We also demonstrated the first catalytic phenylthiometylation of ketones and aldehydes. Unfortunately, it was impossible to perform this process with any enantioselectivity. However, this method can be used for indirect methylation of carbonyls and works well with acid-sensitive compounds such as dioxanone. We also evaluated the reactivity of various phenylthiomethyl amines towards protonation. We claim that aromatic are a stable class of compounds, which do not undergo acid-catalyzed cleavage of free amine to furnish a reactive carbocation. Lastly, we investigated the reactivity of alpha,beta-unsaturated sulfonates in many metal- and organocatalyzed reactions. We evaluated their reactivity and assembled a general procedure for the sulfa-Michael addition of aromatic thiols to (E)-sulfonates. However, this group of compounds turned out to be not very reactive and little similarities to nitroolefins can be postulated. We were able to obtain SMA-products with generally good yields and with enantiomeric excesses up to 64%. We observed that with the increase of enantioselectivity the reaction rate decreased. We also observed that more sterically hindered acceptors gave lower enantiomeric excess. The studies here represent the first activation of sulfonates via hydrogen bond formation with chiral thioureas. We also demonstrated that bifunctional catalysts are the catalysts of choice for many organocatalyzed processes. Furthermore, the reactivity of alpha,beta-unsaturated sulfonates in various reactions has been evaluated. It has been shown that organocatalyzed reactions with carbon nucleophiles (enamine-catalyzed Michael addition, addition of malonates) were impossible to perform. Moreover, our efforts to perform MBH-reactions with benzaldeyde or Henry reactions with different nitro compounds were unsuccessful. In general, alpha,beta-unsaturated sulfonates were not reactive under various reactions conditions with different catalytic systems.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2008

Author dc:creator

• Hoffman, Krzysztof

Contributors dc:contributor

• Enders, Dieter

• info:eu-repo/classification/ddc/540
• Organokatalyse
• Sulfonate
• Chemische Synthese
• Asymmetrische Synthese
• Biomimetische Synthese
• Chemie
• asymmetric
• organocatalysis
• sulfonates
• hydrogenbonding

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113438%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A51123