Peptide Modification via N‑Terminal-Residue-Directed γ‑C(sp³)−H Arylation

Postassembly modification of peptides via C(sp³)−H functionalization provides an efficient way to prepare functionalized peptides for biological study and pharmaceutical development. In this work, we developed a new method for γ-C(sp³)−H functionalization of aliphatic side chains of N-terminus-unprotected peptides. With the N-terminal residues as directing groups, a wide range of di-, tri-, tetra-, and pentapeptides underwent C−H arylation of the residues (Val, Ile, Tle) at the +2 position from the N-terminus.