Endogenous Group‐Directed Late‐Stage C−H Functionalization of Peptides

Peptides are diverse in terms of their functional groups and side‐chain functionalities, and late‐stage C−H functionalization plays a crucial role in their design. Approaches for such synthesis require pre‐installation and post‐removal of the directing group (DG). In recent times, chemical methods have been developed, focusing on the external DG‐free C−H functionalization of peptides. These approaches utilize the inherent native functionality of peptides as DG to simplify synthetic routes, reducing synthetic steps, waste generation, enhancing sustainability, cost‐effectiveness, and operational flexibility. Such approaches facilitate late‐stage C−H functionalization of both natural and unnatural amino acid‐containing peptides.