Metal-free alcohol-directed regioselective heteroarylation of remote unactivated C(sp3)–H bonds
Xinxin Wu1 , Hong Zhang1 , Nana Tang1 , Zhen Wu1 , Dongping Wang1 , Meishan Ji1 , Yan Xu1 , Min Wang1 & Chen Zhu 1,2（朱晨）
1 Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 RenAi Road, Suzhou, Jiangsu 215123, China.
2 Key Laboratory of Synthesis Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, 345 Lingling Road, Shanghai 200032, China.
NATURE COMMUNICATIONS，(2018) 9:3343
Construction of C–C bonds via alkoxy radical-mediated remote C(sp3)–H functionalization is largely unexplored, as it is a formidable challenge to directly generate alkoxy radicals from alcohols due to the high bond dissociation energy (BDE) of O–H bonds. Disclosed herein is a practical and elusive metal-free alcohol-directed heteroarylation of remote unactivated C(sp3)–H bonds. Phenyliodine bis(trifluoroacetate) (PIFA) is used as the only reagent to enable the coupling of alcohols and heteroaryls. Alkoxy radicals are readily generated from free alcohols under the irradiation of visible light, which trigger the regioselective hydrogen-atom transfer (HAT). A wide range of functional groups are compatible with the mild reaction conditions. Two unactivated C–H bonds are cleaved and one new C–C bond is constructed during the reaction. This protocol provides an efficient strategy for the late-stage functionalization of alcohols and heteroaryls.