Visible-light-mediated late-stage N-functionalization of unprotected peptides: introducing the aza-Zimmerman–O'Connell–Griffin reaction†

Abstract

Amides represent a crucial class of compounds in organic chemistry, forming key structural components of biologically significant molecules such as amino acids and peptides. There is a growing need for sustainable methods to synthesize amides that do not rely on coupling reagents or extensive derivatization of carbonyl compounds. In this context, we present an alternative approach for amide synthesis and α-amino acid and peptide functionalization, utilizing the ketene intermediate generated through the photomediated Zimmerman–O'Connell–Griffin (ZOG) rearrangement. This method offers a more sustainable route for late-stage functionalization of peptides, with potential applications in medicinal chemistry, providing a greener alternative to conventional synthetic strategies.