Copper-Mediated Nucleophilic Desulfurization of Thiols

We report a general method for the desulfurization-mediated nucleophilic substitution of thiols. This transformation proceeds under mild conditions using readily available copper salts and accommodates a broad range of nucleophiles. This protocol enables the direct C–X bond formation without requiring thiol preactivation or harsh reagents by leveraging the innate reactivity of C(sp3)-S bonds. The reaction demonstrates high chemoselectivity and functional group tolerance, providing a valuable strategy for late-stage molecular editing and access to noncanonical motifs from abundant thiol-containing sub-strates.