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

Highly diastereo- and enantioselective 1,6-addition of 1,3-ketoamides to p-quinone methides (p-QMs) using chiral NHCs as BrOnsted 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 beta-ketoamides and functionalized p-QMs are applicable to the reaction. Synthetic application of the method is demonstrated via the preparation of highly enantioenriched and gamma-lactam derivatives.