Photochemical Deracemization of N‐Carboxyanhydrides En Route to Chiral α‐Amino Acid Derivatives

Abstract

Readily accessible, racemic N‐carboxyanhydrides (NCAs) of α‐amino acids underwent a deracemization reaction upon irradiation at λ = 366 nm in the presence of a chiral benzophenone catalyst. The enantioenriched NCAs (up to 98% ee) serve as activated α‐amino acid surrogates and, due to their instability, they were directly converted into consecutive products. N‐Protected α‐amino acid esters were obtained after reaction with MeOH and N‐benzoylation (14 examples, 70%‐quant., 82‐96% ee). Other consecutive reactions included amide (ten examples, 65%‐quant., 90‐98% ee) and peptide (three examples, 75‐89%, d.r. = 97/3 to 94/6) bond formation. Limitations of the method relate for some NCAs to issues with solubility, photooxidation, and high configurational lability.