Functionalization of amino acids and peptides via rhodium-catalyzed C-H activation

The great potential of transition metal-catalyzed C-H activation has been used in the construction of natural products, bioactive molecules and functional materials. Due to the high efficiency, selectivity and functional-group tolerance of rhodium, rhodium-catalyzed C-H activation reactions have been widely explored. Recently, rhodium-catalyzed C-H activation was successfully employed in the late-stage diversification of amino acids and peptides, providing an important complementary strategy. This review will offer an introduction to rhodium-catalyzed C-H activation for the preparation of unnatural amino acids and peptides, helping researchers to find indirect connections and disclose hidden opportunities. It will also facilitate the emergence of novel synthetic strategies for the functionalization of amino acids and peptides relying on C-H activation. © 2025 Elsevier B.V., All rights reserved.