Photocatalytic Activation of Elemental Sulfur Enables a Chemoselective Three-Component Thioesterification

A mild and chemoselective three-component thioesterification using olefins, α-ketoacids, and elemental sulfur has been developed. The photocatalytic activation of elemental sulfur, a cheap and abundant sulfur source, enables the rapid installation of a sulfur atom into molecules, reactions that ordinarily would require the use of reactive and malodorous sulfur-containing compounds such as thiols and thioacids. This novel reaction is characterized by high yields and a broad substrate scope, which enables the introduction of thioester moieties into complex molecules including a steroid, a peptide, and a nonprotected glycoside. Mechanistic studies indicated that the success of this transformation depends on the multiple roles played by the elemental sulfur, including those of a sulfurizing agent, a terminal oxidant, and a HAT mediator.