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

Abstract

Despite the growing interest in the synthesis of fluorinated organic compounds, few methods are able to incorporate fluoride ion directly into alkyl C-H bonds. Here, we report the C(sp 3 )-H fluorination reactivity of a formally copper(III) fluoride complex. The C-H fluorination intermediate, LCuF, along with its chloride and bromide analogs, LCuCl and LCuBr, were prepared directly from halide sources with a chemical oxidant and fully characterized. While all three copper(III) halide complexes capture carbon radicals efficiently to afford C(sp 3 )-halogen bonds, LCuF is two orders of magnitude more efficient at hydrogen atom abstraction (HAA) than LCuCl and LCuBr. Alongside reported kinetic data for other LCu(III) species, we established a positive correlation between ligand basicity and the rate of HAA. 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.Carbon-fluorine bonds are becoming increasingly prevalent in pharmaceuticals and agrochemicals. 1 The value of fluorinated compounds in these applications stems from their enhancement of lipophilicity, metabolic stability, and receptor binding affinity. 2

Direct synthetic routes to functionalised crown ethers

“…Compound 10 was also reported by Bower et al 56 In this work, a formally copper(III) fluoride complex (LCuF) performed both the hydrogen atom abstraction and radical capture roles. Upon mixing 3 and LCuF in a 8 : 1 ratio in dichloromethane, product 10 was obtained in 35% yield (Scheme 6).…”

Copper catalyzed late-stage C(sp3)-H functionalization of nitrogen heterocycles

“…The bis(phenyl)sulfonamide radical then abstracts a hydrogen atom from C(sp 3 )-H adjacent to nitrogen of compound 1 to generate the corresponding radical A. In Path I, a radical chain propagation process is proposed, which is supported by recent work on alkyl radical fluorination 51,52 , especially the work on fluorine transfer to alkyl radical from N-F reagents 51 reaction to generate the fluorination intermediate B 53,54 with regeneration of L/Cu(I) complex. Finally, the fluorinated intermediate B undergoes a nucleophilic substitution promoted by NH(SO 2 Ph) 2 via the iminium intermediate C to afford the final CDC product 2 with elimination of HF 54 .…”

The wavelength dependence of Sgr A * size and the unified model of compact radio sources

“…The high brightness temperatures of compact, flat-spectrum radio sources (Bower & Backer 1998;Nagar, Wilson, & Falcke 2001;Ulvestad & Ho 2001) may be explained by a maser amplification of thermal radio emission. A maser mechanism of emission is supported by a rapid variability of total and polarized flux density on timescales less than 2 months (Bower et al 2001). Such a variability is characteristic for non-saturated maser sources.…”