Synthesis of beta-Substituted gamma-Aminobutyric Acid Derivatives through Enantioselective Photoredox Catalysis

摘要

beta-Substituted chiral gamma-aminobutyric acids feature important biological activities and are valuable intermediates for the synthesis of pharmaceuticals. Herein, an efficient catalytic enantioselective approach for the synthesis of -substituted -aminobutyric acid derivatives through visible-light-induced photocatalyst-free asymmetric radical conjugate additions is reported. Various beta-substituted gamma-aminobutyric acid analogues, including previously inaccessible derivatives containing fluorinated quaternary stereocenters, were obtained in good yields (42-89%) and with excellent enantioselectivity (90-97% ee). Synthetically valuable applications were demonstrated by providing straightforward synthetic access to the pharmaceuticals or related bioactive compounds (S)-pregabalin, (R)-baclofen, (R)-rolipram, and (S)-nebracetam.