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Photoredox-Catalyzed N-Directed Regioselective Difluoroalkylation of Unactivated C(sp<sup>3</sup>)–H Bonds

Xi Chen, Zhe Zhang, Wei‐Yu Shi, Yanan Ding, Yu‐Yong Luan, Yan‐Chong Huang, Qiang Wang, Xue‐Yuan Liu, Yong‐Min Liang

2023Organic Letters32 citationsDOI

Abstract

We report a redox-neutral, visible-light-mediated difluoroalkylation of unactivated C(sp 3 )–H bonds in amides via nitrogen-centered radicals triggered intramolecular hydrogen atom transfer. Notably, all types (tertiary, secondary, and primary) of γ-C(sp 3 )–H bonds displayed excellent reactivity. This methodology presents a facile route for the regioselective introduction of α,α-difluoroketone fragments into organic molecules. Moreover, the resulting gem -difluoroketones can be readily converted to structurally diverse difluoro-containing molecules, offering broad potential applications in medicinal chemistry and chemical biology.

Topics & Concepts

RegioselectivityChemistryIntramolecular forceReactivity (psychology)Photoredox catalysisMoleculeRadicalHydrogen bondPrimary (astronomy)CatalysisNitrogen atomCombinatorial chemistryHydrogen atomStereochemistryPhotochemistryMedicinal chemistryOrganic chemistryGroup (periodic table)PhotocatalysisAstronomyMedicineAlternative medicinePathologyPhysicsFluorine in Organic ChemistryRadical Photochemical ReactionsCatalytic C–H Functionalization Methods