Electrically Driven N(_sp ²)- C(_sp ^2/3) Bond Cleavage of Sulfonamides

Sulfonamides are a privileged class of functional groups in medicinal chemistry and an important class of protecting groups in organic synthesis. We report the discovery and development of unexpected electrically driven N(sp²)-C(sp²) and N(sp²)-C(sp³) bond cleavage reactions alongside a dehydrogenative C-O bond coupling reaction under batch and electroflow conditions. Intra-molecular trapping experiments with the diuretic hydrochlorothiazide gave insight into the intermediacy of an N-sulfonyliminium ion en route to the related drug metabolite, chlorothiazide. Using only electrons as the oxidant, this is a green and sustainable technological advancement for sulfonamide deprotection chemistry and drug metabolism studies.