A step-wise reduction of nonracemic α-ketoamides to α-methine amides under mild conditions

A step-wise reductive method that converts nonracemic γ-chiral α-ketoamides into amide derivatives was developed under mild conditions. The method involves a highly efficient three-step transformation including NaBH4-reduction, bromination and Pd/C hydrogenation reactions. As a consequence, a variety of nonracemic γ-diaryl amides products were obtained in high overall yields with excellent enantiomeric specificity. The utility of the method is demonstrated through the concise formal synthesis of (+)-sertraline in good overall yield. [Display omitted]