Hydrothiolation

Hydrothiolation is the chemical reaction in which a thiol (R-SH) adds across an unsaturated carbon–carbon bond, typically a carbon–carbon double bond (alkene) or triple bond (alkyne), to form a thioether. It is a subset of thiol-ene chemistry and is widely used to introduce sulfur-containing linkages in organic synthesis and materials science.

In alkenes, hydrothiolation furnishes alkyl thioethers. Under radical or photochemical conditions, the thiol adds in a way that often places the sulfur on the less substituted carbon (anti-Markovnikov orientation), with subsequent hydrogen transfer delivering the thioether product. Ionic or metal-catalyzed variants can alter regioselectivity and enable more controlled outcomes, including differences in stereochemistry for substituted substrates.

In alkynes, hydrothiolation yields vinyl sulfides. The reaction can be sensitive to the catalyst and conditions, influencing regioselectivity (which carbon of the triple bond receives the sulfur) and, in some cases, the geometry of the resulting vinyl sulfide (E or Z). Terminal and internal alkynes can behave differently under various catalytic systems.

Mechanistically, hydrothiolation proceeds via radical or ionic/catalytic pathways. Radical processes typically involve thiyl radicals (RS•) adding to the unsaturated bond, followed by hydrogen atom transfer. Metal-catalyzed hydrothiolation uses various metals (such as palladium, nickel, copper, or ruthenium) to promote selective addition and control over regiochemistry and stereochemistry.

Applications of hydrothiolation include the synthesis of thioethers for pharmaceuticals and natural products, and the formation of polymer networks and surface-anchored materials through thiol-ene-type click chemistry. The method provides a versatile route to incorporate sulfur functionality across carbon–carbon multiple bonds.