thioetherification

Thioetherification is a set of chemical reactions that form thioether bonds (R–S–R') by introducing sulfur from thiols or related sulfur-containing species into a carbon framework. It is used to install sulfurbearing linkages found in many natural products, pharmaceuticals, and materials.

Several general strategies are employed. Nucleophilic substitution, where a thiolate anion generated from a thiol displaces a leaving group on an alkyl halide or sulfonate, is a classical route to simple thioethers. Thiol-ene reactions form thioethers by the radical or photoinitiated addition of a thiol across carbon–carbon multiple bonds, a widely used approach in polymer chemistry. Transition-metal-catalyzed carbon–sulfur cross-couplings, including palladium- or nickel-catalyzed reactions between aryl or vinyl electrophiles and thiols, provide robust routes to aryl and vinyl thioethers on diverse substrates. In some contexts, radical or photoredox catalysis enables thioetherification under mild conditions.

Applications include the synthesis of drug candidates, agrochemicals, and functional materials; late-stage functionalization of complex molecules; and the preparation of thioether-containing polymers and ligands.

Key challenges include controlling chemoselectivity in multifunctional substrates, avoiding oxidation of thiols to disulfides, managing odor and handling considerations, and developing broadly tolerant catalytic systems for cross-couplings.

Related terms include thiolation and thioether cross-coupling.