Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Angew Chem Int Ed Engl. 2021 Mar 1;60(10):5467-5474. doi: 10.1002/anie.202012263. Epub 2021 Jan 15.
A mild and operationally simple C(sp )-H trifluoromethylation method was developed for unactivated alkanes by utilizing a bench-stable Cu complex, bpyCu(CF ) , as the initiator of the visible-light photoinduced reaction, the source of a trifluoromethyl radical as a hydrogen atom transfer reagent, and the source of a trifluoromethyl anion for functionalization. The reaction was initiated by the generation of reactive electrophilic carbon-centered CF radical through photoinduced homolytic cleavage of bpyCu(CF ) , followed by hydrogen abstraction from an unactivated C(sp )-H bond. Comprehensive mechanistic investigations based on a combination of experimental and computational methods suggested that C-CF bond formation was enabled by radical-polar crossover and ionic coupling between the resulting carbocation intermediate and the anionic CF source. The methylene-selective reaction can be applied to the direct, late-stage trifluoromethylation of natural products and bioactive molecules.
发展了一种温和且操作简便的 C(sp )-H 三氟甲基化方法，该方法利用稳定的 Cu 配合物 bpyCu(CF ) 作为可见光光诱导反应的引发剂、三氟甲基自由基的来源（作为氢原子转移试剂）以及三氟甲阴离子的来源（用于功能化），实现对未活化烷烃的三氟甲基化。反应通过 bpyCu(CF ) 的光诱导均裂产生亲电性的碳中心 CF 自由基引发，随后从未活化的 C(sp )-H 键中抽氢。基于实验和计算方法相结合的综合机理研究表明，C-CF 键的形成是通过自由基-极性转换和生成的碳正离子中间体与阴离子 CF 源之间的离子偶联来实现的。该反应具有亚甲基选择性，可直接对天然产物和生物活性分子进行后期三氟甲基化。
