有机化学 ›› 2022, Vol. 42 ›› Issue (1): 147-159.DOI: 10.6023/cjoc202108006 上一篇    下一篇

研究论文

镍促进电化学还原交叉偶联合成偕二氟烯烃

常哲, 王佳鑫, 陆熹*(), 傅尧*()   

  1. 中国科学技术大学应用化学系 合肥 230026
  • 收稿日期:2021-08-06 修回日期:2021-09-05 发布日期:2021-09-14
  • 通讯作者: 陆熹, 傅尧
  • 基金资助:
    国家自然科学基金(21732006); 国家自然科学基金(51821006); 国家自然科学基金(51961135104); 中国科学技术大学双一流研究基金(YD3530002002)

Synthesis of gem-Difluoroalkenes through Nickel-Promoted Electrochemical Reductive Cross-Coupling

Zhe Chang, Jiaxin Wang, Xi Lu(), Yao Fu()   

  1. Department of Applied Chemistry, University of Science and Technology of China, Hefei 230026
  • Received:2021-08-06 Revised:2021-09-05 Published:2021-09-14
  • Contact: Xi Lu, Yao Fu
  • Supported by:
    National Natural Science Foundation of China(21732006); National Natural Science Foundation of China(51821006); National Natural Science Foundation of China(51961135104); Research Funds of the Double First-Class Initiative of University of Science and Technology of China(YD3530002002)

偕二氟烯烃是一类重要的含氟有机化合物, 在有机合成化学和药物化学研究领域展现出独特的结构优势. 例如, 偕二氟烯基可以便利地转化为单氟烯基、二氟烷基、三氟甲基以及其他多种含氟结构. 偕二氟烯基结构作为羰基理想的电子等排体在药物设计研究中也有广泛的应用. 报道了一种镍促进的电化学还原交叉偶联反应合成功能化的偕二氟烯烃. 该反应在非分隔电解槽中进行, 在温和的电化学还原条件下, 实现了三氟甲基烯烃烯丙基脱氟、氧化还原活性羧酸酯脱羧或者烷基卤化物脱卤素的有机结合. 反应可有效避免使用化学计量的金属粉末或有机还原剂. 该反应为含偕二氟烯基功能结构的生物活性分子提供了有效的合成途径.

关键词: 偕二氟烯烃, 三氟甲基烯烃, 氧化还原活性羧酸酯, 烷基卤化物, 还原交叉偶联, 电化学

gem-Difluoroalkenes are important fluorine-containing compounds with structural superiority in organic synthetic chemistry and medicinal chemistry. For instance, the gem-difluoroethylene moiety could be converted to monofluoroalkenyl, difluoroalkyl, trifluoromethyl moiety, and many other fluorine-containing structures conveniently. The gem-difluoroethylene moiety is also an ideal carbonyl group bioisostere and has already been widely used in drug design. Herein, a nickel-promoted electrochemical reductive cross-coupling to access functionalized and substituted gem-difluoroalkenes is reported. This reaction enables the combination of allylic defluorination of trifluoromethyl alkenes and decarboxylation of redox-active esters or dehalogenation of alkyl halides under mild electrochemical reduction conditions and in an undivided cell, therefore obviates the use of stoichiometric amount metal powder or organic reductants. Furthermore, this reaction provides efficient access to biologically interesting molecules containing gem-difluoroethylene moiety.

Key words: gem-difluoroalkene, trifluoromethyl alkene, redox-active ester, alkyl halide, reductive cross-coupling, electrochemistry