Accelerating sulfonyl fluoride synthesis through electrochemical oxidative coupling of thiols and potassium fluoride in flow
Yiran Cao, Benjamin Adriaenssens, Aloisio de Andrade Bartolomeu, Gabriele Laudadio, Kléber T. de Oliveira, Timothy Noël
Abstract
Abstract Sulfonyl fluorides are valuable synthetic motifs which are currently of high interest due to the popularity of the sulfur (VI) fluoride exchange (SuFEx) click chemistry concept. Herein, we describe a flow chemistry approach to enable their synthesis through an electrochemical oxidative coupling of thiols and potassium fluoride. The reaction can be carried out at room temperature and atmospheric pressure and the yield of the targeted sulfonyl fluoride, by virtue of the short inter-electrode distance between a graphite anode and a stainless-steel cathode, reached up to 92% in only 5 min residence time compared to 6 to 36 h in batch. A diverse set of thiols (7 examples) was subsequently converted in flow. Finally, a fully telescoped process was developed which combines the electrochemical sulfonyl fluoride synthesis with a follow-up SuFEx reaction.