Liu Guo-Kai, Li Xin, Qin Wen-Bing, Peng Xiao-Shui, Wong Henry N C, Zhang Linxing, Zhang Xinhao
School of Pharmaceutical Sciences, Shenzhen University Health Science Centre, Shenzhen University, 3688 Nanhai Ave., Shenzhen 518060, China.
Department of Chemistry, the Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Chem Commun (Camb). 2019 Jul 4;55(52):7446-7449. doi: 10.1039/c9cc03487k. Epub 2019 Jun 5.
A facile and practical approach for the difluoromethylation of aliphatic alcohols with an S-(difluoromethyl)sulfonium salt was developed. A wide variety of alcohols with broad functional groups are compatible to furnish the corresponding alkyl difluoromethyl ethers in good to excellent yields under mild reaction conditions. Control experiments and DFT computational studies suggest that the difluoromethylation of alcohols mainly proceeds via a difluorocarbene pathway involving a five-membered transition state with the participation of water, whose crucial role in this reaction was also elucidated by control experiments.
开发了一种使用S-（二氟甲基）锍盐对脂肪醇进行二氟甲基化的简便实用方法。各种具有广泛官能团的醇在温和的反应条件下都能兼容，以良好至优异的产率提供相应的烷基二氟甲基醚。对照实验和密度泛函理论（DFT）计算研究表明，醇的二氟甲基化主要通过涉及五元过渡态且有水参与的二氟卡宾途径进行，对照实验也阐明了水在该反应中的关键作用。
