Metal‐Free Electrochemical C(Sp ³ )‐H/S‐H Cross‐Coupling of Xanthenes With Thiols: Cysteine‐Selective Functionalization

ABSTRACT

A metal‐free and oxidant‐free electrochemical C(sp ³ )‐H/S‐H cross‐coupling between xanthenes and thiols has been developed under mild conditions. This protocol enables the efficient thiolation of xanthene scaffolds and allows cysteine‐selective functionalization of protected dipeptide fragments. The reaction proceeds at room temperature, exhibits good functional‐group compatibility toward protected peptide functionalities, and can be readily performed on gram scale. Mechanistic studies including control experiments, cyclic voltammetry, and EPR analysis support a radical‐involved electrochemical oxidation pathway. This work expands the scope of electrochemical thiol‐based cross‐dehydrogenative coupling reactions and provides a sustainable approach to the construction of C─S bonds in bio‐relevant molecular settings.