Asymmetric oxidative rearrangement of indoles enabled by dual catalysis with in situ generated acyl hypoiodite and chiral phosphoric acid

Abstract

Although oxidative halogenation approaches have reached remarkable levels of sophistication, reports on the use of inorganic halides as pre-catalysts for the asymmetric synthesis of enantioenriched molecules have remained elusive. Herein, we disclose a dual-catalytic strategy for achieving a mild and enantioselective protocol for the synthesis of optically active oxindoles via the oxidative rearrangement of indoles. The proper choice of the oxidant–halide system and the chiral catalyst employed is crucial for high reactivity and enantioselectivity. Mechanistic studies indicate that acyl hypoiodite as the key active species to react with indoles is generated catalytically in situ and chiral phosphoric acid functions as an efficient resolving catalyst for the corresponding dynamic kinetic resolution of the resultant 3-iodo indolenines. The successful execution of the dual-catalytic strategy triggered by the utilization of halonium intermediates as traceless handles provides a significant conceptual advantage and will serve as a useful foundation for further investigations into cooperative stereocontrolled halide-catalyzed transformations.