Synthesis of 3‐(Trifluoromethyl)indoles by Oxidative Cyclization of o‐Sulfonamido‐α‐(trifluoromethyl)styrenes

Abstract

3‐(Trifluoromethyl)indoles were successfully synthesized by cyclization through intramolecular oxidative C−H/N−H coupling of α‐(trifluoromethyl)styrenes bearing a sulfonamido group at the ortho‐position. On treatment with cerium (IV) ammonium nitrate (CAN) in tert‐butyl alcohol, o‐sulfonamido‐α‐(trifluoromethyl)styrenes underwent oxidative cyclization assisted by microwave irradiation to afford the corresponding 3‐trifluoromethylated indoles. By using this method, 3‐(trifluoromethyl)indoles bearing various substituents were obtained in high yields. We assumed that the reaction proceeded through (i) radical 5‐endo‐trig cyclization of intermediary aminyl radical cations, generated by one‐electron oxidation of the sulfonamide nitrogen, and (ii) subsequent another one‐electron oxidation, followed by deprotonation.