Dynamic Kinetic Asymmetric Reductive Amination: Synthesis of Chiral Primary β-amino Lactams.

A highly efficient ruthenium-catalyzed asymmetric reductive amination (ARA) of racemic -keto lactams with molecular hydrogen and ammonium salts is disclosed for the synthesis of enantiomerically pure primary amino lactams through dynamic kinetic resolution (DKR). By this approach, a range of syn primary -amino lactams were obtained in high yields with high chemo-, enantio-, and diastereoselectivity (up to 98% yield, 99%ee, >20:1 d.r., syn products). The utility of the products has been demonstrated by rapid access to a key synthetic intermediate towards biologically active drug molecules. Meanwhile, mechanistic studies and control experiments indicate that the reaction may proceed through the hydrogenation of an iminium intermediate.