Electrochemical Nickel-Catalyzed Selective Inter- and Intramolecular Arylations of Cysteine-Containing Peptides

Here we report a simple electrochemical route towards the synthesis of S-arylated peptides by a site selective coupling of peptides with aryl halides under base free conditions. This approach demonstrates the power of electrochemistry to access both highly complex peptide conjugates and cyclic peptides. A practical electrochemical Ni-catalytic system has been developed for selective (hetero)arylation, alkenylation and alkynylation of cysteine-containing peptides. The high functional group compatibility and application to the synthesis of cyclic peptides either by cyclization or stapling demonstrate the potential protocol's utility in medicinal chemistry and chemical biology.**image