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

Abstract

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.

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Supplementary material

Supporting Information
Supporting Information
Cif file of compound 3f
Cif file of compound 3f