Application Progress of Langlois Reagent in Electrochemical Trifluoromethylation Reactions

doi:10.6023/cjoc202506034

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (10): 3534-3545.DOI: 10.6023/cjoc202506034 Previous Articles Next Articles

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Langlois试剂在电化学三氟甲基化反应中的应用进展

何卫保^a, 易荣楠^b^,^*(), 杨梓^c^,^*(), 伍智林^d^,^*(), 何卫民^d^,^*()

^a 湖南化工职业技术学院技术与职业教育研究中心株洲 412000
^b 湖南警察学院食药环及毒品检验技术湖南省普通高等学校重点实验室长沙 410138
^c 长沙医学院功能核酸基础与临床湖南省普通高校重点实验室长沙 410219
^d 南华大学化学化工学院衡阳 421001

收稿日期:2025-06-28 修回日期:2025-07-23 发布日期:2025-08-26
基金资助:
长沙市自然科学基金(104872)

Application Progress of Langlois Reagent in Electrochemical Trifluoromethylation Reactions

Weibao He^a, Rongnan Yi^b^,^*(), Zi Yang^c^,^*(), Zhilin Wu^d^,^*(), He^d^,^*()

^a Research Center for Technical and Vocational Education Studies, Hunan Chemical Vocational Technology College, Zhuzhou 412000
^b Key Laboratory of Food & Environment & Drug Monitoring and Testing of Universities in Hunan Province, Hunan Police Academy, Changsha 410138
^c Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, Changsha Medical University, Changsha 410219
^d School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001

Received:2025-06-28 Revised:2025-07-23 Published:2025-08-26
Contact: * wuzhilin@usc.edu.cn; weiminhe@usc.edu.cn; yrn@hnu.edu.cn; yangziycy@163.com
Supported by:
Changsha Natural Science Foundation(104872)

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

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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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Fig. & Tab. 13

Scheme 1. Examples of drug molecules with CF3 group

Figure 1. Existing trifluoromethylation strategies

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

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

Scheme 4. Electrochemical trifluoromethylation of tryptophan containing oligopeptides

Scheme 5. Electrochemical trifluoromethylation of alkynes

Scheme 6. Electrochemical trifluoromethylation/spirocyclization of N-benzylacrylamides

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

Scheme 8. Electrochemical synthesis of trifluoromethylated pyrrolidines

Scheme 9. Electrochemical decarboxylative trifluoromethylation of cinnamic acids

Scheme 10. Stereoselective migratory heteroaryltrifluoromethylation of allylic amines via electrosynthesis

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

Scheme 12. Electrochemical trifluoromethylation of thiophenols

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Langlois试剂在电化学三氟甲基化反应中的应用进展

Application Progress of Langlois Reagent in Electrochemical Trifluoromethylation Reactions

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