Enantioselective access to chiral aliphatic amines and alcohols via Ni-catalyzed hydroalkylations

Chiral aliphatic amine and alcohol derivatives are ubiquitous in pharmaceuticals, pesticides, natural products and fine chemicals, yet difficult to access due to the challenge to differentiate between the spatially and electronically similar alkyl groups. Herein, we report a nickel-catalyzed enantioselective hydroalkylation of acyl enamines and enol esters with alkyl halides to afford enantioenriched alpha -branched aliphatic acyl amines and esters in good yields with excellent levels of enantioselectivity. The operationally simple protocol provides a straightforward access to chiral secondary alkyl-substituted amine and secondary alkyl-substituted alcohol derivatives from simple starting materials with great functional group tolerance. Chiral aliphatic amine and alcohol derivatives are difficult to access due to the challenge to differentiate between spatially and electronically similar alkyl groups. Here the authors show a nickel-catalyzed enantioselective hydroalkylation of acyl enamines and enol esters with alkyl halides to afford enantioenriched alpha -branched aliphatic acyl amines and esters in good yields with excellent enantioselectivity.

Automated summary

Chiral aliphatic amine and alcohol derivatives are difficult to access due to the challenge to differentiate between spatially and electronically similar alkyl groups. By utilizing a nickel-catalyzed enantioselective hydroalkylation, enantioenriched alpha-branched aliphatic acyl amines and esters can be efficiently synthesized with good yields and excellent enantioselectivity.