Highly enantioselective aza-Baylis-Hillman reactions catalyzed by chiral thiourea derivatives

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.