Manganese-Mediated Electrochemical Oxidation of Thioethers to Sulfoxides Using Water as the Source of Oxygen Atoms

Oxygen-atom transfer reactions are a prominent class of synthetic redox reactions that often use high-energy oxygen-atom donor reagents. Electrochemical methods can bypass these reagents by using water as the source of oxygen atoms through pathways involving direct or indirect (mediated) electrolysis. Here, manganese porphyrins and related mediators are shown to be effective molecular electrocatalysts for selective oxidation of thioethers to sulfoxides, without overoxidation to the sulfone. The reactions proceed by proton-coupled oxidation of a Mn^III-OH₂ species to generate a Mn^IV-OH and Mn^V═O species. This methodology is compared to direct electrolysis methods initiated by single-electron oxidation of the thioether, and chloride-mediated electrochemical oxidation of thioethers. The Mn-mediated reactions operate at lower applied potential and exhibit improved substrate scope and functional group compatibility relative to direct electrolysis, and the tunability of the Mn-based mediators allows for improved performance relative to chloride-mediated electrolysis. An electrochemical parallel screening platform is developed and applied to a library of pharmaceutically relevant thioethers.