Highly Enantioselective Aza‐Baylis–Hillman Reactions Catalyzed by Chiral Thiourea Derivatives

A series of aromatic imines was found to undergo coupling with methyl acrylate with unprecedented levels of enantioselectivity, albeit only in modest yields, and a mechanistic analysis based on the identity of this intermediate as well as kinetic investigations and isotope studies are provided.

Abstract

Abstract We report the discovery of asymmetric aza‐Baylis–Hillman (ABH) reactions of N‐p‐ nitrobenzenesulfonylimines with methyl acrylate catalyzed by chiral thiourea derivatives. A series of aromatic imines was found to undergo coupling with methyl acrylate with unprecedented levels of enantioselectivity (87–99% ee), albeit only in modest (25–49%) yields. A DABCO‐acrylate‐imine adduct was isolated as a key intermediate in the ABH reaction. We provide a mechanistic analysis based on the identity of this intermediate as well as kinetic investigations and isotope studies, and propose a rationale for the observed limitations in yield. Synthetic applications of the ABH products are also described.