Direct activation of sulfides by C–H oxidation with photoexcited nitroarenes: Formal manipulations of the C–S bond

Abstract

The sulfide motif is distributed widely across chemical and biological space. In synthesis, its installation often marks the end point of a sequence, due to its relative inertness; sulfides typically require direct oxidation of sulfur before they are receptive towards transformation. Unfortunately, selective S-oxidation is not always straightforward, with the need for oxidants lacking chemoselectivity in the presence of functionality and delivering mixtures of oxidation products. This multi-step manipulation of the sulfide motif, initiated by direct S-oxidation, limits the use of sulfides as synthetic handles for downstream manipulation. Herein, we describe a direct activation of sulfides by C–H oxidation alpha to sulfur – rather than traditional oxidation at sulfur – that facilitates efficient formal C–S bond manipulation. The mild nature of the photo-induced anaerobic oxidation protocol enables its merger with high-value transformations in telescoped or one-pot protocols that deliver branched amines, secondary alcohols, and alkenes from aldehyde and ketone intermediates. The method expands the chemistry of sulfides by diverting reactivity away from sulfur (oxidation, alkylation) and instead targeting directly the alpha position, resulting in formal manipulation of the C–S bond, and redefining sulfides as latent synthetic handles to be “switched on” at will.