Sulfonamide-directed site-selective functionalization of unactivated C(sp3)−H enabled by photocatalytic sequential electron/proton transfer

• DOI: 10.1038/s41467-024-49337-3
• Publication Date: 2024-06-14T09:21:39Z
• Authors: Chaodong Wang; Zhi Chen; Jie Sun; Luwei Tong; Wenjian Wang; Shengjie Song; Jianjun Li
• Keywords: Surface Modification; Sulfonamide; Proton-Coupled Electron Transfer

Abstract The generation of alkyl radical from C(sp 3 )−H substrates via hydrogen atom abstraction represents a desirable yet underexplored strategy in alkylation reaction since involving common concerns remain adequately unaddressed, such as the harsh conditions, limited substrate scope, and employment noble metal- or photo-catalysts stoichiometric oxidants. Here, we utilize synergistic photoredox transfer (HAT) catalysis to accomplish general practical functionalization unactived centers with broad high functional group compatibility, operational simplicity. A combination validation experiments density theory reveals that N-centered radicals, generated free N − H bond stepwise electron/proton event, are key intermediates enable an intramolecular 1,5-HAT intermolecular HAT process for nucleophilic carbon-centered radicals formation achieve heteroarylation, alkylation, amination, cyanation, azidation, trifluoromethylthiolation, halogenation deuteration. value this protocol is further demonstrated by gram-scale synthesis late-stage natural products drug derivatives.