Electrochemical Enantioselective Oxidation of Indoles via Chiral Phosphoric Acid Catalysis in Cooperation with H₃PO₄ in Aqueous Media

Disclosed here is the first catalytic enantioselective electrochemical oxidative rearrangement of indoles for the efficient synthesis of highly enantioenriched spirooxindoles. The in-situ generated HBr from substrate oxidation, known to be detrimental to the reaction itself, was perfectly consumed by cathode reduction. Challenges of this process include the difficulty in maintaining the synergy between substrate oxidation and cathode reduction as well as the general incompatibility of a hydrogen bonding catalytic system with the aqueous acidic media. A monophasic system was initially developed, but with little substrate generality. Further analysis of the mechanism and careful optimization allowed the development of a much more general and robust biphasic system that exhibited multiple advantages over chemical oxidation, including broader scope, less waste, milder conditions, and better enantioselectivity. It is also the first demonstration of chiral phosphoric acid catalysis in cooperation with H₃PO₄ in acidic aqueous media. © 2025 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH