Langlois试剂在电化学三氟甲基化反应中的应用进展

doi:10.6023/cjoc202506034

摘要/Abstract

在药物分子设计中, 含氟基团的引入能够显著改善分子的亲脂性、代谢稳定性以及膜穿透能力. 电化学三氟甲基化作为一种绿色高效的合成策略, 已成为构建含三氟甲基分子的重要手段. 作为最具代表性的三氟甲基化试剂, Langlois试剂凭借其原料易得、反应条件温和、操作简便等优势, 在电化学介导的有机小分子三氟甲基化反应中展现出广阔的应用前景. 从C—H键的三氟甲基化、O—H三氟甲基化以及S—H三氟甲基化三个方向, 系统评述了近5年该试剂在电化学三氟甲基化反应中的应用进展, 重点关注反应机理、区域选择性和底物适用性等关键科学问题.

关键词: Langlois试剂, 电化学合成, 三氟甲基化, 反应机理

In drug molecule design, the introduction of fluorinated groups can significantly improve the lipophilicity, metabolic stability, and membrane penetration ability of molecules. Electrochemical trifluoromethylation, as a green and efficient synthesis strategy, has become an important means of constructing trifluoromethyl containing molecules. As the most representative trifluoromethylation reagent, Langlois reagent has shown broad application prospects in electrochemically mediated trifluoromethylation reactions of small organic molecules due to its advantages of easy availability of raw materials, mild reaction conditions, and easy operation. This article systematically reviews the research progress of this reagent in electrochemical trifluoromethylation reactions in the past five years from three directions: C—H bond trifluoromethylation, O—H trifluoromethylation, and S—H trifluoromethylation, with a focus on key scientific issues such as reaction mechanism, regioselectivity, and substrate applicability.

Key words: Langlois reagent, electrochemical synthesis, trifluoromethylation, reaction mechanism

引用此文

何卫保, 易荣楠, 杨梓, 伍智林, 何卫民. Langlois试剂在电化学三氟甲基化反应中的应用进展[J]. 有机化学, 2025, 45(10): 3534-3545.

Weibao He, Rongnan Yi, Zi Yang, Zhilin Wu, He. Application Progress of Langlois Reagent in Electrochemical Trifluoromethylation Reactions[J]. Chinese Journal of Organic Chemistry, 2025, 45(10): 3534-3545.

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图/表 13

图式1. 含CF3的药物分子示例

Scheme 1. Examples of drug molecules with CF3 group

图1. 现有三氟甲基化策略

Figure 1. Existing trifluoromethylation strategies

图式2. 电化学合成2-芳基-3-三氟甲基-2H-吲唑类化合物

Scheme 2. Electrochemical synthesis of 2-phenyl-3-(trifluoromethyl)-2H-indazoles

图式3. 电化学合成3-三氟甲基喹喔啉-2(1H)-酮类化合物

Scheme 3. Electrochemical synthesis of 3-(trifluoromethyl)quinoxalin-2(1H)-ones

图式4. 含色氨酸寡肽的电化学三氟甲基化

Scheme 4. Electrochemical trifluoromethylation of tryptophan containing oligopeptides

图式5. 炔烃的电化学三氟甲基化

Scheme 5. Electrochemical trifluoromethylation of alkynes

图式6. N-苄基丙烯酰胺的电化学三氟甲基化/螺环化反应

Scheme 6. Electrochemical trifluoromethylation/spirocyclization of N-benzylacrylamides

图式7. N-烯丙基酰胺的电化学氧化环化合成含CF3的苯并噁嗪

Scheme 7. Electrochemical oxidative cyclization of N-allylamides for the synthesis of CF3-containing benzoxazines

图式8. 三氟甲基吡咯烷的电化学合成

Scheme 8. Electrochemical synthesis of trifluoromethylated pyrrolidines

图式9. 肉桂酸的电化学脱羧三氟甲基化

Scheme 9. Electrochemical decarboxylative trifluoromethylation of cinnamic acids

图式10. 电化学驱动烯丙基胺的立体选择性迁移杂芳基三氟甲基化

Scheme 10. Stereoselective migratory heteroaryltrifluoromethylation of allylic amines via electrosynthesis

图式11. 缺电子苯酚O-三氟甲基化的电合成

Scheme 11. Electrosynthesis for O-trifluoromethylation of electron-deficient phenols

图式12. 硫酚的电化学三氟甲基化

Scheme 12. Electrochemical trifluoromethylation of thiophenols

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