Catalytic Asymmetric Intermolecular Stetter Reactions of Eeolizable Aldehydes with Nitrostyrenes: Computational Study Provides Insight into the Success of the Catalyst

摘要

Over the past decade, N-heterocyclic carbenes (NHCs) have been used as catalysts in a variety of C-C bond forming reactions. Our group has been interested in the development of chiral NHCs as catalysts for the asymmetric intramolecular Stetter reaction and more recently, the intermolecular variant. We recently reported that hetaryl aldehydes and enals react efficiently with nitroalkenes in the Stetter reaction, leading to β-nitro ketones with high enantioselectivity. Crucial to the success of this method was the development of a fluorinated triazolium salt pre-catalyst that provides significantly enhanced enantioselectivity over des-fluoro analogues.' Although the new catalyst system greatly expands the scope of this method, these conditions are not amenable to the use of unactivated aliphatic aldehydes. Because of their lower electrophilicity relative to aryl aldehydes, aliphatic aldehydes have rarely been successfully used in the asymmetric intermolecular Stetter reaction.