Difluoromethylation of Unactivated Alkenes Using Freon-22 through Tertiary Amine-Borane-Triggered Halogen Atom Transfer

作者：Zhi‐Qi Zhang, Yueqian Sang, Cheng‐Qiang Wang, Peng Dai, Xiao‐Song Xue, Jared L. Piper, Zhi-Hui Peng, Jun‐An Ma, Fa‐Guang Zhang, Jie Wu · 发表于：Journal of the American Chemical Society · 年份：2022 · DOI：10.1021/jacs.2c05356 · 被引用次数：157 · 研究领域：Fluorine in Organic Chemistry、Inorganic Fluorides and Related Compounds、Radical Photochemical Reactions

The application of abundant and inexpensive fluorine feedstock sources to synthesize fluorinated compounds is an appealing yet underexplored strategy. Here, we report a photocatalytic radical hydrodifluoromethylation of unactivated alkenes with an inexpensive industrial chemical, chlorodifluoromethane (ClCF 2 H, Freon-22). This protocol is realized by merging tertiary amine-ligated boryl radical-induced halogen atom transfer (XAT) with organophotoredox catalysis under blue light irradiation. A broad scope of readily accessible alkenes featuring a variety of functional groups and drug and natural product moieties could be selectively difluoromethylated with good efficiency in a metal-free manner. Combined experimental and computational studies suggest that the key XAT process of ClCF 2 H is both thermodynamically and kinetically favored over the hydrogen atom transfer pathway owing to the formation of a strong boron–chlorine (B–Cl) bond and the low-lying antibonding orbital of the carbon–chlorine (C–Cl) bond.