Carbene catalyzed asymmetric nucleophilic acylations with novel triazolium salts

We have developed a practical and efficient synthesis of a family of new chiral trazolium salts from (S)-glutamic acid. With access to the new precarbene catalysts we started to verify their ability to promote the benzoin condensation and intramolecular Stetter reaction. The optimal conditions were identified and allowed for an expansion of the reaction scope with 8-95% yield and enantiomeric excesses of 21-95% in the benzoin condensation. Furthermore, these carbene precatalysts have been applied to intramolecular Stetter reaction with good efficiency and moderate selectivity. Based on the strategy of carbene design, we have developed different N-substituted triazolium salts, which successfully catalyzed the intermolecular Stetter reaction. The structure of 1-Methyl triazolidine was elucidated by X-ray structure analysis. Moreover, we have demonstrated that 1-methyl triazolidine lacked catalytic activity in the intermolecular Stetter reaction. In the processes of searching the optimal carbene generating high enantioselectivities, we prepared a variety of chiral, nucleophilic carbenes which has benefited from the expected impact of the fused ring, N-based substituent and nature of the side chain steric demand. Finally, after screening different conditions, we were able to obtain the 1,4 diketones in moderate to excellent yields (49 98%) and moderate to good enantioselectivities (56 78% ee), which could be enhanced by one recrystallization to excellent levels (90 99% ee). In addition, examination of the reaction course revealed new mechanistic insights about the formation of the Stetter product. We have extended the intermolecular Stetter reaction to a variety of electron rich aldehydes coupled to a variety of Michael acceptors. In this context, we have developed the asymmetric version of the addition of heterocyclic aldehydes to arylidene-malonates catalyzed by N-heterocyclic carbenes, which afforded chiral polycarbonyl compounds in good yields (>85%) and good enantioselectivities (up to 78% ee). More importantly, excellent enantiomeric excesses (up to >99% ee) were obtained after single recrystallization. Furthermore, this method can open a practical entry to develop gram-scale nucleophilic acylation products for polycarbonyl compounds, which could used for synthesizing potential precursors of enzymatic inhibitors.The intramolecular benzoin condensation to synthesize natural products (-)-eucomol have been explored.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2008

Author dc:creator

• Han, Jianwei

Contributors dc:contributor

• Enders, Dieter

• info:eu-repo/classification/ddc/540
• Stetter-Reaktion
• Acylierung
• Chemie
• nucleophile Carbene
• Triazoliumsalze
• nucleophilic carbene
• Stetter reaction
• Triazolium salts
• nucleophilic acylation

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113070%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A50530