Non-Enzymatic Hybrid Catalysis for Stereoconversion of l-Amino Acid Derivatives to d-Isomers

A catalytic transformation of N-unprotected l-amino esters to N-protected d-amino esters was developed. The combined use of a heteroaromatic aldehyde, Lewis acid, palladium complex, and chiral Brønsted acid was a key factor for the successful operation of this catalytic system. The synergistic cooperation of an appropriate aldehyde and Lewis acid was crucial for promoting an efficient racemization of l-amino esters, while the combination of a palladium complex and chiral phosphoric acid enabled dynamic kinetic resolution through asymmetric N-allylation, providing N-protected d-amino esters in good yields with up to 97 : 3 er. Following appropriate deprotection processes, d-amino acids were obtained without loss of enantiomeric purity.