Direct Asymmetric Reductive Amination

Abstract

Asymmetric reductive amination of β-keto amides catalyzed by the chiral catalyst Ru(OAc)₂((R)-dm-segphos) produces unprotected β-amino amides with high yields and high enantioselectivities (94.7?99.5% ee). This “one-pot” methodology is general in substrate scope and has been successfully employed to produce sitagliptin with 99.5% ee and 91% assay yield. The excellent reaction efficiency is attributed to the remarkable tolerance to high concentrations of ammonium ion, the high chemoselectivity, and the high enantioselectivity (99.5% ee) of the Ru catalyst system.