可见光诱导三氟甲基化研究进展: 三氟乙酸与三氟乙酸酐作为廉价高效的三氟甲基化试剂

doi:10.6023/cjoc202603009

摘要/Abstract

三氟甲基在医药、农药和材料科学多方面的重要作用, 推动了三氟甲基化合成方法及三氟甲基试剂的研发. 可见光催化的三氟甲基化作为一种绿色高性能的合成策略, 已成为构建含三氟甲基分子的重要手段, 展现出广阔的应用前景. 围绕廉价高效的三氟甲基试剂三氟乙酸及三氟乙酸酐在可见光条件下的活化转化, 从预合成中间体活化、由活化试剂原位活化和直接活化三个方向, 系统评述了近十年该领域的研究进展, 梳理其发展历程, 阐述活化方式、反应机制及转化类型等关键科学问题, 旨在为该领域未来催化策略的理性设计提供参考.

关键词: 三氟甲基化, 三氟乙酸及三氟乙酸酐, 可见光催化, 配体金属电荷转移

The trifluoromethyl group plays a crucial role in pharmaceuticals, agrochemicals, and materials science, driving extensive efforts in the discoveries of new trifluoromethylating reagents and the development of methods for introducing this group into molecular frameworks. Visible-light photocatalytic trifluoromethylation, as a green and efficient synthetic strategy, has emerged as an important method for constructing trifluoromethyl-containing molecules with broad application prospects. The research progress of exploring on trifluoroacetic acid and its anhydride as inexpensive and effective trifluoromethyl reagents for visible-light catalyzed trifluoromethylation reactions is systematically reviewed. It focuses on key scientific issues such as activating methods, reaction mechanisms, and transformations. The insights gained are expected to facilitate the rational design of effective photocatalytic strategies for future utilization of trifluoroacetic acid or its anhydride.

Key words: trifluoromethylation, trifluoroacetic acid and its anhydride, visible-light photocatalysis, ligand-to-metal charge transfer (LMCT)

引用此文

黄斌, 许展图, 陈静, 苏伟平, 朱晨. 可见光诱导三氟甲基化研究进展: 三氟乙酸与三氟乙酸酐作为廉价高效的三氟甲基化试剂[J]. 有机化学, 2026, 46(9): 3461-3479.

Bin Huang, Zhantu Xu, Jing Chen, Weiping Su, Chen Zhu. Advances in Visible-Light Induced Trifluoromethylation with Trifluoroacetic Acid and Its Anhydride as Inexpensive and Effective Trifluoromethylation Reagents[J]. Chinese Journal of Organic Chemistry, 2026, 46(9): 3461-3479.

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图/表 20

图式1. 预合成三氟甲基肟酯NHBC酯和脂肪烯烃的光诱导的氢三氟甲基化和芳香迁移反应

Scheme 1. Photoinduced hydrotrifluoromethylation and aryl migration reaction with NHBC ester

图式2. 预合成双功能试剂二苯甲酮肟酯实现的光催化的烯烃的亚氨三氟甲基化

Scheme 2. Photocatalytic imino-trifluoromethylation with alkene via pre-synthesized bifunctional oxime esters

图3. 预合成咪唑鎓磺酸盐IMDN-SO2CF3实现的光诱导的烯烃氟烷基硼化和吡啶苄基位的三氟甲基化

Scheme 3. Photoinduced fluorocarboborylation and C(sp3)—H trifluoromethylation of azines via pre-synthesized imidazolium sulfonatereagent IMDN-Tf

图式4. 预合成三氟甲磺酸吡啶盐TFSP实现的光诱导的烯烃双官能化反应

Scheme 4. Photoinduced difunctionalizations of alkenes via pre-synthesized trifluoromethylsulfonyl-pyridinium salt TFSP

图式5. 预合成全氟芳香三氟乙酸碘盐的光氧化还原脱羧以实现芳香族化合物的三氟甲基化

Scheme 5. Photoredox decarboxylation of pre-synthesized perfluoroarene iodine(III) trifluoroacetates for trifluoromethylation of (hetero)arenes

图式6. 预合成阳离子芳香磺酸酯作为可见光引发的自由基光笼实现生物分子的快速三氟甲基化

Scheme 6. Rapid biomolecular trifluoromethylation using pre-synthesized cationic aromatic sulfonate esters as visible-light-triggered radical photocages

图式7. 吡啶氮氧化合物原位活化三氟乙酸酐实现的光氧化还原脱羧三氟甲基化

Scheme 7. Photoredox decarboxylation of trifluoroacetic anhydride for trifluoromethylation using pyridine N-oxide as in-situ activator

图式8. 吡啶氮氧化合物参与构建EDA复合物实现的三氟乙酸酐光氧化还原脱羧三氟甲基化

Scheme 8. Photoredox decarboxylation of trifluoroacetic anhydride for trifluoromethylation using EDA complex derived from pyridine N-oxide acceptor via EDA mechanism

图式9. 丙酮肟三氟乙酸酯的极性反转实现的光催化芳香化合物三氟甲基化和烯烃的氧化三氟甲基化

Scheme 9. Photocatalytic trifluoromethylation of (hetero)arenes and oxy-trifluoromethylation of alkene enabled by the acid-triggered reactivity umpolung of acetoxime esters

图式10. 二苯基亚砜原位活化三氟乙酸光氧化还原脱羧实现的三氟甲基化

Scheme 10. Photoredox decarboxylation of trifluoroacetic acid for trifluoromethylation using diaryl sulfoxide as activator

图式11. 吡啶原位活化三氟甲磺酸酐实现的光催化三氟甲基化

Scheme 11. Photocatalytic trifluoromethylation using pyridine in-situ activating trifluoromethanesulfonic anhydride

图式12. 膦原位活化三氟甲磺酸酐实现的对惰性烯烃和炔烃的光催化氢三氟甲硫基化

Scheme 12. Photocatalytic hydrotrifluoromethylthiolation of unactivated alkenes and alkynes using phosphine in-situ activating trifluoro-methanesulfonic anhydride

图式13. 吡啶原位活化三氟甲磺酸酐实现的光催化吡啶三氟甲基化

Scheme 13. Photocatalytic trifluoromethylative pyridylation of alkenes using pyridine in-situ activating triflic anhydride

图式14. 无活化试剂参与的光催化三氟乙酸酐实现的三氟甲基化

Scheme 14. Photocatalytic trifluoromethylation using trifluoroacetic anhydride with absence of activator

图式15. 由LMCT介导的脱羧过程

Scheme 15. LMCT-mediated decarboxylation

图式16. 布朗酸解锁LMCT的铁催化三氟甲基化

Scheme 16. Iron photocatalytic trifluoromethylation via Brønsted acid-unlocked LMCT

图式17. 双配体铁光催化烯烃的氯化/氟化三氟甲基化

Scheme 17. Dual ligand-enabled iron photocatalysis for chloro/fluoro-polyhaloalkylation of alkenes

图式18. 光诱导的铁催化LMCT脱羧过程实现氟烷基化的喹诺酮的合成

Scheme 18. Photo-induced synthesis of fluoroalkylated quinolinones via iron-catalyzed LMCT decarboxylation process

图式19. 铁LMCT催化机制实现的三氟乙酸直接脱羧

Scheme 19. Direct decarboxylation of trifluoroacetates enabled by iron catalyzed LMCT

图式20. 银盐的LMCT介导的光电催化三氟甲基化

Scheme 20. Electrophotocatalytic trifluoromethylation by LMCT excitation of Ag(II) trifluoromethyl carboxylates

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