化学学报 ›› 2018, Vol. 76 ›› Issue (12): 913-924.DOI: 10.6023/A18070306 上一篇    下一篇

所属专题: 有机氟化学

研究展望

不对称三氟甲硫基化反应研究进展

李树森a, 王剑波a,b   

  1. a. 北京大学化学与分子工程学院 生物有机与分子工程教育部重点实验室 北京分子科学国家研究中心 北京 100871;
    b. 中国科学院上海有机化学研究所 金属有机化学国家重点实验室 上海 200032
  • 收稿日期:2018-07-30 出版日期:2018-12-15 发布日期:2018-08-29
  • 通讯作者: 王剑波,E-mail:wangjb@pku.edu.cn E-mail:wangjb@pku.edu.cn
  • 作者简介:李树森,2017年本科毕业于中国科学技术大学.目前在北京大学化学与分子工程学院攻读博士学位.主要从事羰基化合物α位不对称三氟甲基化反应的研究;王剑波,1983年本科毕业于南京理工大学;1990年获日本北海道大学博士学位;1990年至1993年在瑞士日内瓦大学从事博士后研究;1993年至1995年在美国威斯康星大学从事博士后研究;1995年至今在北京大学化学与分子工程学院开展独立研究工作.主要从事过渡金属催化的卡宾转移、卡宾偶联以及基于卡宾的高分子聚合等研究.
  • 基金资助:

    项目受国家自然科学基金(No.21332002)和国家重点基础研究发展计划(973计划,No.2015CB856600)资助.

Recent Advance in Asymmetric Trifluoromethylthiolation

Li Shu-Sena, Wang Jianboa,b   

  1. a. Beijing National Laboratory of Molecular Sciences (BNLMS) and Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University, Beijing 100871;
    b. State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032
  • Received:2018-07-30 Online:2018-12-15 Published:2018-08-29
  • Contact: 10.6023/A18070306 E-mail:wangjb@pku.edu.cn
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 21332002) and the National Basic Research Program of China (973 Program, No. 2015CB856600).

三氟甲硫基吸电子能力强、脂溶性高,在药物分子内引入三氟甲硫基可以显著地提高化合物的细胞膜穿透性与代谢稳定性.而不同立体异构的药物分子会有不同的药理活性,因此不对称三氟甲硫基化反应在近几年内逐渐受到化学家们的重视.目前,这一领域还处于发展的初步阶段,本文将就目前为止已经发展的不对称三氟甲硫基化方法做简单的总结,包括使用亲电的三氟甲硫基试剂和使用含三氟甲硫基的合成砌块这两种不同的策略.最后对不对称三氟甲硫基化领域所存在的挑战进行简单的展望.

关键词: 三氟甲硫基化, 不对称催化, 有机氟化合物, 立体选择性, 有机合成

Fluorine-containing groups can modulate the physicochemical and biological properties of organic molecules. Consequently, the synthesis of fluorinated organic molecules has attracted considerable attention in the field of pharmaceuticals, agrochemicals and material sciences. Among fluorine-containing groups, the trifluoromethylthio group has the highest Hansch’s hydrophobicity parameter and remarkable electron-withdrawing character. The incorporation of a trifluoromethylthio group into organic molecules can significantly enhance their membrane permeability and metabolic stability because of its high lipophilicity and strong electron-withdrawing effect. As a result, various methods have been involved to synthesize SCF3-containing compounds using electrophilic or nucleophilic trifluoromethylthio reagents. On the other hand, the chirality of pharmaceutical molecules has an important effect on their properties, and different stereoisomers of a pharmaceutical molecules always have dramatically different pharmaceutical activities. Thus, the asymmetric trifluoromethylthiolation of organic molecules is of growing interest in recent years. Up to now, this field is still in the stage of initial development. In this perspective article, we will briefly summarize the methods of asymmetric trifluoromethylthiolation of organic molecules that have been reported so far. Two different strategies including the use of electrophilic trifluoromethylthiolating reagents and the use of trifluoromethylthio-containing building blocks will be introduced. Employing electrophilic trifluoromethylthiolating reagents, the enantioselective trifluoromethylthiolation of β-ketoesters, oxindoles as well as alkenes have been developed using Cinchona alkaloid, copper(Ⅱ) or indane-based chiral sulfide/selenide as the catalyst. Alternatively, using trifluoromethylthiolated building blocks is another approach to establish chiral centers bearing the trifluoromethylthio group. In this approach, an asymmetric trifluoromethylthiolation via enantioselective [2,3]-sigmatropic rearrangement of a sulfonium ylide generated from SCF3-containing sulfide and metal carbene has been disclosed using chiral Rh(Ⅱ) and Cu(I) as the catalyst. Finally, we will discuss the challenges of the asymmetric trifluoromethylthiolation of organic molecules in the future.

Key words: trifluoromethylthiolation, asymmetric catalysis, organofluorine compounds, stereoselectivity, organic synthesis