A photoredox catalyzed Kornblum oxidation reaction for unnatural amino acid synthesis

Abstract

Unnatural amino acids are important building blocks in organic synthesis and drug discovery. They are also frequently integrated into peptides or proteins for biological studies. However, the direct and simplified synthesis of UAAs remains a great challenge. At the same time, many known peptide modifications are based on carbon–heteroatom bonds. There are no general methods for peptide modification via the construction of C–C bonds. To address this challenge, herein we propose that styrene could serve as an alternative alkene substrate for the synthesis of UAAs, leveraging the p–π conjugation-assisted effect to generate intermediates to build the C–C bond. This protocol has obvious advantages such as good functional group tolerance, biocompatible reaction conditions, and retained stereochemistry. This strategy was successfully utilized for the synthesis of unnatural amino acids and direct modifications of peptides.