Catalytic Michael/Ring-Closure Reaction of alpha,beta-Unsaturated Pyrazoleamides with Amidomalonates: Asymmetric Synthesis of (-)-Paroxetine

摘要

A highly enantioselective tandem Michael/ring-closure reaction of alpha,beta-unsaturated pyrazoleamides and amidomalonates has been accomplished in the presence of a chiral N, N'-dioxide-Yb(OTf)(3) complex (Tf: trifluoromethanesulfonyl) to give various substituted chiral glutarimides with high yields and diastereo-and enantioselectivities. Moreover, this methodology could be used for gram-scale manipulation and was successfully applied to the synthesis of (-)-paroxetine. Further nonlinear and HRMS studies revealed that the real catalytically active species was a monomeric L-PMe2-Yb3+ complex. A plausible transition state was proposed to explain the origin of the asymmetric induction.