Copper-Catalyzed Asymmetric C(sp³)–H Benzylation: Stereoselective Synthesis of Unnatural Aromatic Amino Acids

The general synthesis of chiral unnatural aromatic amino acids has rarely been reported. We herein describe a visible light-promoted copper-catalyzed enantioselective C(sp³)-H benzylation of glycine derivatives. The method demonstrated compatibility in coupling various <i>N</i>-hydroxyphthalimide (NHP) esters derived from aromatic acids with glycine derivatives, providing a general protocol for synthesizing analogues of phenylalanine, tryptophan, and tyrosine. This protocol features mild conditions, high enantioselectivity, excellent functional group tolerance, and important impacts on the development of peptide drugs.