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Enantio‐ and Diastereoselective NiH‐Catalyzed Hydroalkylation of Enamides or Enecarbamates with Racemic <i>α</i>‐Bromoamides**

Jian Chen, Lifu Wu, Yue Zhao, Shaolin Zhu

2023Angewandte Chemie International Edition29 citationsDOIOpen Access PDF

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 (enamides or enecarbamates) 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 to generate an enantiomerically enriched alkylnickel(II) species. Subsequent enantioconvergent alkylation with a racemic alkyl electrophile generates the desired product as a single stereoisomer.

Topics & Concepts

StereocenterElectrophileEnantioselective synthesisAlkylationChemistryVicinalCatalysisAlkylOrganic chemistryStereochemistryCatalytic C–H Functionalization MethodsAsymmetric Hydrogenation and CatalysisSynthesis and Catalytic Reactions
Enantio‐ and Diastereoselective NiH‐Catalyzed Hydroalkylation of Enamides or Enecarbamates with Racemic <i>α</i>‐Bromoamides** | Litcius