Rhodium-Catalyzed Asymmetric Conjugate Addition to γ-Substituted α,β-Unsaturated γ-Lactams through Dynamic Kinetic Resolution: Asymmetric Synthesis of trans-β,γ-Disubstituted γ-Lactams

Abstract

The reaction of racemic γ-substituted α,β-unsaturated γ-lactams rac-1 with arylboron reagents 2 in the presence of a chiral diene L1a–rhodium catalyst under basic conditions (3.0 equiv of NEt3) gave high yields of β,γ-disubstituted trans-γ-lactams 3 with both high diastereo- and enantioselectivity. Fast racemization of 1 by way of a dienolate generated with the base followed by kinetic resolution of 1 with the chiral rhodium catalyst realized this highly efficient dynamic kinetic resolution. The synthetic utility of the present method is demonstrated by the synthesis of key intermediates to biologically active compounds.