Transition-metal-free Chemoselective Oxidative C-C Coupling of the sp3 C-H Bond of Oxindoles with Arenes and Addition to Alkene: Synthesis of 3-Aryl Oxindoles, and Benzofuro- and Indoloindoles

Abstract

A transition-metal (TM)-free and halogen-free NaOtBu-mediated oxidative cross-coupling between the sp³ C-H bond of oxindoles and sp² C-H bond of nitroarenes has been developed to access 3-aryl substituted and 3,3-aryldisubstituted oxindoles in DMSO at room temperature in a short time. Interestingly, the sp³ C-H bond of oxindoles could also react with styrene under TM-free conditions for the practical synthesis of quaternary 3,3-disubstituted oxindoles. The synthesized 3-oxindoles have also been further transformed into advanced heterocycles, that is, benzofuroindoles, indoloindoles, and substituted indoles. Mechanistic experiments of the reaction suggests the formation of an anion intermediate from the sp³ C-H bond of oxindole by tert-butoxide base in DMSO. The addition of nitrobenzene to the in-situ generated carbanion leads to the 3-(nitrophenyl)oxindolyl carbanion in DMSO which is subsequently oxidized to 3-(nitro-aryl) oxindole by DMSO.

Keywords: carbanion; cross-coupling; nitrobenzene; oxindoles; styrene; transition-metal-free.