Electro-induced C-H/S-H Cross-Coupling for the Functionalization/Macrocyclization of Cysteine-Containing Peptides

The electrochemical platform that underpins the promising future of selective electrochemical modifications of peptides and proteins, however, is still rather underdeveloped. Here in, an electro-induced umpolung approach that enables the efficient functionalization/macrocyclization of cysteine-containing peptides is reported. Notably, this method utilizes simple halogen source and takes metal-mediated halogen atom transfer as the main pathway to enable the in-situ polarity reversal, highlighting the unique possibilities associated with electrochemical activation methods. Under simple and mild conditions, cysteine residue can be well-labelled with high chemo-selectivity and excellent conversion. This transformation can tolerate a wide range of valuable enamines, azoles, and peptides partners, and can also be utilized as a macrocyclization tactic for cyclic peptide synthesis and other areas.