Preparation of difluoromethylthioethers through difluoromethylation of disulfides using TMS-CF2H

Abstract

We report an operationally simple, metal-free approach for the late-stage introduction of the important lipophilic hydrogen-bond donor motif, SCF₂H. This reaction converts diaryl- and dialkyl-disulfides into the corresponding aryl/alkyl–SCF₂H through the nucleophilic transfer of a difluoromethyl group with good functional group tolerance. This method is notable for its use of commercially available TMSCF₂H, and does not rely on the need for handling of sensitive metal complexes.