Catalytic Michael/Ring-Closure Reaction of α,β-Unsaturated Pyrazoleamides with Amidomalonates: Asymmetric Synthesis of (-)-Paroxetine.

A highly enantioselective tandem Michael/ring-closure reaction of α,β-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.