Enantioselective Stetter Reactions of Enals and Modified Chalcones Catalyzed by N-Heterocyclic Carbenes

摘要

Organocatalytic activation of readily available substrates has led to the rapid development of many enantioselective reactions in the last decade. In N-heterocyclic carbene (NHC) catalysis, reactions of enals with enones or enone derivatives have been extensively investigated and are reported to undergo a diverse set of transformations based on the catalytically generated enolate and homoenolate equivalents as intermediates. In contrast, the NHC-catalyzed enantioselective Stetter-type Michael additions of enals to enones remain challenging in part due to the competing and often dominant homoenolate or enolate pathways. Herein we report an enantioselective Stetter reaction of enals and modified chalcones using triazolium-based NHC catalysts Eq. (1). The previously reported typical homoenolate and enolate pathways were largely suppressed especially when β-alkyl enals were used as the acyl anion precursors and alkylidene diketones as the Michael acceptors. Enals having two β substituents can also behave as effective acyl anion precursors. A relevant and elegant enantioselective Stetter reaction between enals and nitro-alkenes using NHC and catechol cocatalysts was reported by Rovis and co-workers recently.