Linking Stereocenters Together: Enantio- and Diastereoselective NiH-Catalyzed Hydroalkylation of Internal Alkenes with Racemic Alkyl Electrophiles

Catalytic methods which control multiple stereogenic centers simultaneously are highly desirable in modern organic synthesis and chemical manufacturing. Herein, we report a regio-, enantio-, and diastereoselective NiH-catalyzed hydroalkylation process which proceeds with simultaneous control of vicinal stereocenters originating from two readily accessible partners, prochiral internal alkenes (N-acyl enamines) and racemic alkyl electrophiles (α-bromoamides or Katritzky salts). This reaction produces high-value β-aminoamides and their derivatives under mild conditions and with precise selectivity. Preliminary studies of the mechanism indicate that the reaction involves an enantioselective syn-hydronickelation followed by a diastereoselective radical addition to generate an enantio- and diastereomerically pure dialkylnickel(III) complex. Subsequent stereospecific reductive elimination generates the desired product as a single stereoisomer.