C(sp³)–H Fluorination with a Copper(II)/(III) Redox Couple

Despite the growing interest in the synthesis of fluorinated organic compounds, few reactions are able to incorporate fluoride ions directly into alkyl C–H bonds. Here, we report the C­(sp3)–H fluorination reactivity of a formally copper­(III) fluoride complex. The C–H fluorination intermediate, LCuF, along with its chloride and bromide analogues, LCuCl and LCuBr, were prepared directly from halide sources with a chemical oxidant and fully characterized with single-crystal X-ray diffraction, X-ray absorption spectroscopy, UV–vis spectroscopy, and 1H nuclear magnetic resonance spectroscopy. Quantum chemical calculations reveal significant halide radical character for all complexes, suggesting their ability to initiate and terminate a C­(sp3)–H halogenation sequence by sequential hydrogen atom abstraction (HAA) and radical capture. The capability of HAA by the formally copper­(III) halide complexes was explored with 9,10-dihydroanthracene, revealing that LCuF exhibits rates 2 orders of magnitude higher than LCuCl and LCuBr. In contrast, all three complexes efficiently capture carbon radicals to afford C­(sp3)–halogen bonds. Mechanistic investigation of radical capture with a triphenylmethyl radical revealed that LCuF proceeds through a concerted mechanism, while LCuCl and LCuBr follow a stepwise electron transfer–halide transfer pathway. The capability of LCuF to perform both hydrogen atom abstraction and radical capture was leveraged to enable fluorination of allylic and benzylic C–H bonds and α-C–H bonds of ethers at room temperature.尽管氟化有机化合物的合成领域关注度与日俱增，但能够直接将氟离子嵌入烷基C–H键的反应仍屈指可数。本文报道了一种形式上为铜(III)氟化物配合物(formally copper(III) fluoride complex)的C(sp³)–H氟化反应活性。该C–H氟化中间体LCuF，与其氯代、溴代同系物LCuCl和LCuBr，均可直接由卤化物源与化学氧化剂制备得到，并通过单晶X射线衍射(single-crystal X-ray diffraction)、X射线吸收光谱(X-ray absorption spectroscopy)、紫外-可见光谱(UV–vis spectroscopy)以及¹H核磁共振波谱(¹H nuclear magnetic resonance spectroscopy)完成了全面表征。量子化学计算(quantum chemical calculations)结果显示，所有配合物均表现出显著的卤自由基特性，这暗示它们可通过依次的氢原子转移(hydrogen atom abstraction, HAA)与自由基捕获，引发并终止C(sp³)–H卤化序列。上述形式上为铜(III)的卤化物配合物的氢原子转移能力，通过9,10-二氢蒽(9,10-dihydroanthracene)进行了探究，结果显示LCuF的反应速率比LCuCl和LCuBr高出两个数量级。与之相反，三种配合物均能高效捕获碳自由基，以生成C(sp³)–卤键。通过三苯甲基自由基(triphenylmethyl radical)开展的自由基捕获机理研究表明，LCuF遵循协同反应机理，而LCuCl与LCuBr则遵循分步电子转移-卤离子转移路径。借助LCuF同时具备氢原子转移与自由基捕获的能力，我们实现了室温下烯丙基、苄基C–H键以及醚类α-C–H键的氟化反应。