Acta Chim. Sinica ›› 2018, Vol. 76 ›› Issue (12): 988-996.DOI: 10.6023/A18080334 Previous Articles     Next Articles

Special Issue: 有机氟化学

Article

常见三氟甲基源释放三氟甲基自由基能力的理论计算研究

李曼a, 康会英a, 薛小松a, 程津培a,b   

  1. a. 南开大学元素有机国家重点实验室 化学学院 天津化学化工协同创新中心 天津 300071;
    b. 清华大学化学系 基础分子科学中心 北京 100084
  • 收稿日期:2018-08-14 出版日期:2018-12-15 发布日期:2018-10-08
  • 通讯作者: 薛小松,E-mail:xuexs@nankai.edu.cn E-mail:xuexs@nankai.edu.cn
  • 基金资助:

    项目受国家自然科学基金(Nos.21772098,21390400)、天津化学化工协同创新中心、南开大学元素有机国家重点实验室以及中央高校基本科研业务费专项资金资助.

Computational Study of the Trifluoromethyl Radical Donor Abilities of CF3 Sources

Li Mana, Kang Huiyinga, Xue Xiao-Songa, Cheng Jin-Peia,b   

  1. a. State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China;
    b. Center of Basic Molecular Science, Department of Chemistry, Tsinghua University, Beijing 100084, China
  • Received:2018-08-14 Online:2018-12-15 Published:2018-10-08
  • Contact: 10.6023/A18080334 E-mail:xuexs@nankai.edu.cn
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21772098, 21390400), Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), the State Key Laboratory on Elemento-Organic Chemistry, and the Fundamental Research Funds for the Central Universities.

Organic compounds containing trifluoromethyl (CF3) group(s) are widely prevalent in biochemical and medicinal science. This is mainly due to the fact that the trifluoromethyl group often improves the metabolic stability and lipophilicity of biologically active compounds. The need of efficient methods for the incorporation of this group into target molecules has spurred research to discover new, practical CF3 sources. Among various CF3 sources, the radical trifluoromethylating reagents has provided a strong driving force for the discovery of the novel trifluoromethylation reactions, and contributed enormously to the efficient synthesis of various CF3-containing compounds. Although a wide variety of radical CF3 sources are now available to organic chemists, little attention has been paid to assess their trifluoromethyl radical donor abilities (TR·DA). Moreover, the available radical reagents show a very rich and diverse reactivity. The establishment of an extensive scale to quantify their CF3 radical donating abilities should be of great value for both the rational design of novel reagents and the judicious selection of appropriate reagent to explore new radical reactions. Herein, we present a systematic computational study of the homolytic X―CF3 bond dissociation enthalpies of 35 radical trifluoromethylating reagents by using the SMD-M06-2X/[6-311++G(2df, 2p)-Def2-QZVPPD]//SMD-M06-2X/[6-31+G(d)-LANL2DZ] method, aiming to provide an energetic guide for estimating their trifluoromethyl radical donor abilities. A comprehensive TR·DA scale was constructed, which covers a range from -21.5 to 95.2 kcal·mol-1. The effects of the frequently used activators including single electron transfer reagents and halogen/chalcogen-bond donors on trifluoromethyl radical donor abilities were investigated. The results show that single electron transfer is the most efficient way to promote the CF3 radical release. We expect that the results of this study could be highly valuable for the mechanistic understanding and the rational design of novel CF3 sources and new radical trifluoromethylation reactions.

Key words: radical trifluoromethylating reagent, homolytic bond dissociation enthalpy, structure-reactivity relationship, halogen bond, DFT calculation