Electrically-driven N(sp2)-C(sp2/3) bond cleavage in sulfonamides

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

Abstract

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.

Details

Original languageEnglish
Pages (from-to)3487–3493
JournalACS Sustainable Chemistry & Engineering
Volume8
Issue number8
Early online date10 Feb 2020
Publication statusPublished - 2 Mar 2020

Keywords

  • Electrosynthesis, Dealkylation, Sulfonamide, Oxidation, Shono, Dehydrogenative Coupling