Direct Synthesis of Thioesters from Feedstock Chemicals and Elemental Sulfur

The development of a mild, atom- and step-economical catalytic strategy that effectively generates value-added molecules directly from readily available commodity chemicals is a central goal of organic synthesis. In this context, the thiol–ene click chemistry for carbon–sulfur (C–S) bond construction has found widespread applications in the synthesis of pharmaceuticals and functional materials. In contrast, the selective carbonyl thiyl radical addition to carbon–carbon multiple bonds remains underdeveloped. Herein, we report a carbonyl thiyl radical-based thioester synthesis through three-component coupling from feedstock aldehydes, alkenes, or alkynes and elemental sulfur by direct photocatalyzed hydrogen atom transfer. This method represents an orthogonal strategy to the conventional thiol-based nucleophilic substitution and exhibits a remarkably broad substrate scope ranging from simple commodity chemicals such as ethylene and acetylene to complex pharmaceutical molecules. This protocol can be easily extended to the synthesis of thiolactones, oligomer/polymers, and thioacids. Its synthetic utility has been demonstrated by a two-step synthesis of the drug esonarimod. Mechanistic studies indicate that the use of elemental sulfur to trap acyl radicals is both thermodynamically and kinetically favored, illustrating its great potential for the synthesis of sulfur-containing molecules.