N-Heterocyclic carbenes as chiral Brønsted base catalysts: a highly diastereo- and enantioselective 1,6-addition reaction

Abstract

Highly diastereo- and enantioselective 1,6-addition of 1,3-ketoamides to p-quinone methides (p-QMs) using chiral NHCs as Brønsted base catalysts is developed. The reaction is based on the utilization of a 1,3-ketoamide having acidic N–H that forms a chiral ion-pair consisting of the enolate and the azolium ion. Different β-ketoamides and functionalized p-QMs are applicable to the reaction. Synthetic application of the method is demonstrated via the preparation of highly enantioenriched β and γ-lactam derivatives.