Organocatalytic enantioselective michael addition of 4-hydroxycoumarin to α,β-unsaturated ketones: a simple synthesis of warfarin

A type of C₂-symmetric secondary amine amide catalysts were developed for the asymmetric Michael addition of Ahydroxycoumarin to α,ß-unsaturated ketones. A series of important biologically and pharmaceutically active compounds were obtained in excellent yields (up to 99%) with high enantioselectivities (up to 89%ee) under mild conditions. In addition, enantiopure product could be obtained by a single recrystallization.