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.