Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu, 215123, China.
Key Laboratory of Synthesis Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, 345 Lingling Road, Shanghai, 200032, China.
Nat Commun. 2018 Aug 21;9(1):3343. doi: 10.1038/s41467-018-05522-9.
Construction of C-C bonds via alkoxy radical-mediated remote C(sp)-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(sp)-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.
通过烷氧基自由基介导的远程 C(sp)-H 功能化来构建 C-C 键在很大程度上尚未得到探索，因为由于 O-H 键的高键离解能 (BDE)，直接从醇中生成烷氧基自由基是一项艰巨的挑战。本文公开了一种实用且难以捉摸的无金属醇导向的远程未活化 C(sp)-H 键杂芳基化反应。二(三氟乙酸)苯碘 (PIFA) 被用作唯一的试剂，以实现醇和杂芳基的偶联。在可见光照射下，烷氧基自由基可轻易地从游离醇中生成，引发区域选择性氢原子转移 (HAT)。该反应条件温和，具有广泛的官能团兼容性。在反应过程中，两个未活化的 C-H 键被切断，同时构建了一个新的 C-C 键。该方案为醇和杂芳基的后期官能化提供了一种有效的策略。
