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Visible-Light-Induced C–F Bond Activation for the Difluoroalkylation of Indoles

Scott T. Shreiber, Albert Granados, Bianca T. Matsuo, Jadab Majhi, Mark W. Campbell, Shivani Patel, Gary A. Molander

2022Organic Letters48 citationsDOIOpen Access PDF

Abstract

An aryl disulfide mediated C–F bond activation of the trifluoromethyl group to generate valuable gem- difluoroalkylindoles is described. This method relies on readily available commodity reagents under mild reaction conditions and represents the first transition-metal-free redox-neutral C–F bond activation strategy. The reaction employs various substituted indoles and α-fluoro-substituted esters. Further, this mode of C–F activation was also amenable to the activation of trifluoromethylated arenes for the preparation of bis -benzylic gem -difluoromethylenes between indole and arene substructures, providing access to a unique chemical space.

Topics & Concepts

ChemistryIndole testReagentTrifluoromethylDisulfide bondArylCombinatorial chemistryRedoxMedicinal chemistryStereochemistryOrganic chemistryAlkylBiochemistryFluorine in Organic ChemistryInorganic Fluorides and Related CompoundsRadical Photochemical Reactions
Visible-Light-Induced C–F Bond Activation for the Difluoroalkylation of Indoles | Litcius