One-Pot, Three-Component Synthesis of Sulfides Using a Sulfoxide Reagent as a Sulfur Dication Equivalent

Sulfides are prevalent in bioactive molecules and have also found numerous applications in synthesis. Various reagents have been developed for the three-component synthesis of sulfides, but the strategic use of sulfur dication equivalents for this purpose has been largely overlooked. Here we report a one-pot, three-component synthesis of sulfides exploiting a sulfoxide reagent as a formal sulfur dication equivalent, unlocking new synthetic chemistry of sulfenate anions. Our protocol involves three chemical operations to sequentially form sulfenate anions, sulfenate esters, and sulfides, using two Grignard reagents and trimethylsilyl chloride (TMSCl). We demonstrate a wide range of Grignard reagents to be coupled, thereby allowing the modular synthesis of sulfides, including dialkenyl and alkenyl-alkynyl sulfides.