Fig. 1: Design of a modular enamide/enecarbamate reductive hydroalkylation for the synthesis of chiral aliphatic amines.

a Representative drug molecules demonstrating the universal existence of chiral aliphatic amines in biologically active molecules. b Catalytic asymmetric reductive hydroalkylation of enamides and enecarbamates enables rapid access to the privileged chiral aliphatic amines, complementing mainstream approaches that are limited by auxiliary groups to access satisfactory stereoselectivity. c Synthetic analysis and proposed mechanism of enamide and enecarbamate reductive hydroalkylation. Enamides and enecarbamates are prepared via facile syntheses from bulk chemicals—aldehydes, alkynes and amides. It was assumed that this reaction involved regio- and stereoselective hydrometallation of an enamide or enecarbamate to generate a catalytic amount of enantioenriched alkylnickel intermediate, followed by C–C bond formation with alkyl electrophile to yield chiral amine.