Carbene-Catalyzed Enantioselective Addition of Thioamides to Bromoenals for Access to Thiazinone Heterocycles

Abstract

A carbene-catalyzed reaction between α-bromoenals and thioamides was developed. Key steps include enantioselective 1,4-addition of thioamide sulfur atoms to α,β-unsaturated acyl azolium intermediate. Subsequent intramolecular annulation eventually affords thiazinone heterocycles with high optical purities. The introduction of Lewis acid additives such as Cu(OTf)₂ to this NHC catalytic reaction could provide small but consistent improvements to reaction enantioselectivities.