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

Over the past decade, N-heterocyclic carbenes (NHCs) have been used as catalysts in a variety of C-C bond forming reactions.[1] Our group has been interested in the development of chiral NHCs as catalysts for the asymmetric intra-molecular Stetter reaction[2,3] and more recently the inter-molecular variant.[4,5] We recently reported that hetaryl aldehydes and enals react efficiently with nitroalkenes in the Stetter reaction, leading to β-nitro ketones with high enantioselectivity.[4d] 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.[6] Although this new catalyst system greatly expands the scope of this method, these conditions are not amenable to the use of unactivated aliphatic aldehydes. Due to their lower electrophilicity than aryl aldehydes, aliphatic aldehydes have rarely been used successfully in the asymmetric inter-molecular Stetter reaction.[7,8]