Highly enantioselective synthesis of warfarin and its analogs by means of cooperative LiClO4/DPEN-catalyzed Michael reaction: enantioselectivity enhancement and mechanism

The highly enantioselective synthesis of warfarin and its analogs was reported in this manuscript. And a cooperative catalysis was observed in asymmetric primary amine-catalyzed Michael reaction for the enantioselective synthesis of warfarin and its analogs, which led to the finding of several cooperative catalyst systems combined with Lewis acid and primary amine, such as LiClO4/DPEN. In this Michael reaction of 4-hydrocoumarin, the cooperative catalyst system (LiClO4/DPEN) resulted in higher levels of stereoselectivity (up to 94%ee). Additionally, the mechanism of the enantioselectivity enhancement in the cooperative catalytic Michael reaction has been investigated by using of ESI-MS and the study of nonlinear effect.