Visible-Light-Induced Radical Carbonylative Dearomatization of Unactivated Indoles

Dearomative hydrofunctionalization of indoles represents an appealing strategy to access C(sp³)-rich indoline scaffolds for drug discovery; however, such transformations typically require activated substrates, leaving unactivated indoles largely unexplored. Herein, we report a photochemical radical carbonylative dearomatization of unactivated indoles under visible light irradiation. Central to this protocol is the interception of the highly reactive indolenium intermediate-generated in situ via acid-mediated C3-protonation-through the formation of an electron donor-acceptor (EDA) complex with 4-alkyl-1,4-dihydropyridines (DHPs). This photoactive EDA complex initiates a mechanistically distinct radical pathway that effectively circumvents the detrimental dimerization typically plaguing indolenium intermediates. Subsequent radical carbonylation and radical cross-coupling enable the carbonylative dearomatization of a broad range of indoles with diverse alkyl-DHPs. The method exhibits excellent functional group tolerance and broad substrate scope, furnishing various 2-acylindolines in generally good yields. Comprehensive mechanistic studies, including control experiments, electron paramagnetic resonance spectroscopy, and UV/vis absorption analyses, support a radical-radical coupling mechanism as the key step in this transformation.