Advances in Visible-Light Induced Trifluoromethylation with Trifluoroacetic Acid and Its Anhydride as Inexpensive and Effective Trifluoromethylation Reagents

doi:10.6023/cjoc202603009

Abstract

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)

Cite this article

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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Fig. & Tab. 20

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Scheme 15. LMCT-mediated decarboxylation

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

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

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

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

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

References 65

[1]	Alonso, C.; de Marigorta, E. M.; Rubiales, G.; Palacios, F. Chem. Rev. 2015, 115, 1847. doi: 10.1021/cr500368h
[2]	Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320. doi: 10.1039/B610213C
[3]	Zhang, J.; Jin, C. F.; Zhang, Y. J. Chin. J. Org. Chem. 2014, 34, 662 (in Chinese).
	(张霁, 金传飞, 张英俊, 有机化学, 2014, 34, 662.) doi: 10.6023/cjoc201310039
[4]	Müller, K.; Diederich, C. F. F. Science 2007, 317, 1881. doi: 10.1126/science.1131943 pmid: 17901324
[5]	Qing, F. L.; Liu, X. Y.; Ma, J. A.; Shen, Q. L.; Song, Q. L.; Tang, P. P. CCS Chem. 2022, 4, 2518. doi: 10.31635/ccschem.022.202201935
[6]	Liu, M. J.; Cai, Y. L.; Shi, R. C.; He, Y. M.; He, P. P.; Sun, Y. J.; Gao, X. F.; Hong, L. C.; Yao, S. Y.; Bao, Z. B.; Yang, Q. W.; Ren, Q. L.; Zhang, Z. G. Sci. Sin. Chim 2025, 55, 2828. doi: 10.1360/SSC-2025-0089
[7]	Koike, T. Asian J. Org. Chem. 2020, 9, 529. doi: 10.1002/ajoc.v9.4
[8]	Li, M.; Xue, X. S.; Cheng, J. P. Acc. Chem. Res. 2020, 53, 182. doi: 10.1021/acs.accounts.9b00393
[9]	Jia, H.; Haring, A. P.; Berger, F.; Zhang, L.; Ritter, T. J. Am. Chem. Soc. 2021, 143, 7623. doi: 10.1021/jacs.1c02606
[10]	Liu, S.; Zhou, J.; Yu, L.; Liu, Y. L.; Huang, Y. G.; Ouyang, Y.; Liu, G. K.; Xu, X. H.; Shibata, N. Chem. Rev. 2025, 125, 4603. doi: 10.1021/acs.chemrev.4c00661
[11]	He, W. M.; Wu, Z. L.; Yang, Z.; Yi, R. N.; He, W. B. Chin. J. Org. Chem. 2025, 45, 3534 (in Chinese). doi: 10.6023/cjoc202506034
	(何卫保, 易荣楠, 杨梓, 伍智林, 何卫民, 有机化学, 2025, 45, 3534.)
[12]	Tan, F. F.; Li, Z. C. Front. Chem. 2025, 13, 1602003. doi: 10.3389/fchem.2025.1602003
[13]	Tamaki, S.; Kusamoto, T.; Tsurugi, H. ChemCatChem 2025, 17, e202402106.
[14]	Lin, J.; Li, Z.; Kan, J.; Huang, S. J.; Su, W. P.; Li, Y. D. Nat. Commun. 2017, 8, 14353. doi: 10.1038/ncomms14353
[15]	Chen, Y. X.; He, Y. C.; Gao, Y.; Xue, J. K.; Qu, W.; Xuan, J.; Mo, Y. M. Scienece 2024, 384, 670.
[16]	Qi, J.; Xu, J. H.; Ang, H. T.; Wang, B. B.; Gupta, N. K.; Dubbaka, S. R.; O’Neill,, P.; Mao, X. W.; Lum, Y. W.; Wu, J. J. Am. Chem. Soc. 2023, 145, 24965. doi: 10.1021/jacs.3c10148
[17]	Motornov, V.; Trienes, S.; Resta, S.; Oliveira, J. C. A.; Lin, Z. P.; Liu, Z.; von Münchow, T.; Stückl, C.; Ackermann, L. Angew. Chem., Int. Ed. 2025, 64, e202504143.
[18]	Liang, T.; Neumann, C. N.; Ritter, T. Angew. Chem., Int. Ed. 2013, 52, 8214. doi: 10.1002/anie.v52.32
[19]	Studer, A. Angew. Chem., Int. Ed. 2012, 51, 8950 doi: 10.1002/anie.v51.36
[20]	Garwood, J. J. A.; Chen, A. D.; Nagib, D. A. J. Am. Chem. Soc. 2024, 146, 28034.
[21]	Xiao, H. W.; Zhang, Z. Z.; Fang, Y. W.; Zhu, L.; Li, C. Z. Chem. Soc. Rev. 2021, 50, 6308. doi: 10.1039/D1CS00200G
[22]	Li, L.; Mu, X.; Liu, W.; Wang, Y.; Mi, Z.; Li, C. J. J. Am. Chem. Soc. 2016, 138, 5809. doi: 10.1021/jacs.6b02782
[23]	Lu, B.; Zhang, Z. H.; Jiang, M.; Liang, D.; He, Z. W.; Bao, F. S.; Xiao, W. J.; Chen, J. R. Angew. Chem., Int. Ed. 2023, 62, e202309460.
[24]	Wu, S.; Wu, X. X.; Wang, D.; Zhu, C. Angew. Chem., Int. Ed. 2019, 58, 1499. doi: 10.1002/anie.v58.5
[25]	Zhang, Z. Z.; Zhu, L.; Li, C. Z. Chin. J. Chem. 2019, 37, 452. doi: 10.1002/cjoc.v37.5
[26]	Xu, P.; Fan, W. Z.; Chen, P. H.; Liu, G. S. J. Am. Chem. Soc. 2022, 144, 13468. doi: 10.1021/jacs.2c06432
[27]	Li, Z. L.; Li, C. Y.; Ding, Y.; Huo, H. H. Coord. Chem. Rev. 2022, 460.
[28]	Gu, Q. S.; Li, Z. L.; Liu, X. Y. Acc. Chem. Res. 2020, 53, 170. doi: 10.1021/acs.accounts.9b00381
[29]	Song, L. L.; Cai, L. C.; Gong, L.; Van der Eycken, E. V. Chem. Soc. Rev. 2023, 52, 2358. doi: 10.1039/D2CS00734G
[30]	Lin, J. S.; Dong, X. Y.; Li, T. T.; Jiang, N. C.; Tan, B.; Liu, X. Y. J. Am. Chem. Soc. 2016, 138, 9357. doi: 10.1021/jacs.6b04077
[31]	Depecker, C.; Marzouk, H.; Trevin, S.; Devynckb, J. New J. Chem. 1999, 23, 739. doi: 10.1039/a901305i
[32]	Zhang, W. G.; Zou, Z. L.; Wang, Y. H.; Wang, Y.; Liang, Y.; Wu, Z. G.; Zheng, Y. X.; Pan, Y. Angew. Chem., Int. Ed. 2019, 58, 624. doi: 10.1002/anie.v58.2
[33]	Wu, X. X.; Zhu, C. Acc. Chem. Res. 2020, 53, 1620. doi: 10.1021/acs.accounts.0c00306
[34]	Majhi, J.; Dhungana, R. K.; Renteria-Gomez, A.; Sharique, M.; Li, L. B.; Dong, W. Z.; Gutierrez, O.; Molander, G. A. J. Am. Chem. Soc. 2022, 144, 15871. doi: 10.1021/jacs.2c07170
[35]	Patra, T.; Bellotti,, P.; Strieth-Kalthoff, F.; Glorius, F. Angew. Chem., Int. Ed. 2020, 59, 3172. doi: 10.1002/anie.v59.8
[36]	Zheng, Y.; Liao, Z. H.; Xie, Z. Z.; Chen, H. B.; Chen, K.; Xiang, H. Y.; Yang, H. Org. Lett. 2023, 25, 2129. doi: 10.1021/acs.orglett.3c00577 pmid: 36943094
[37]	Zhang, W. G.; Zou, Z. L.; Zhao, W. X.; Lu, S.; Wu, Z. G.; Huang, M. J.; Wang, X. C.; Wang, Y.; Liang, Y.; Zhu, Y.; Zheng, Y. X.; Pan, Y. Nat. Commun. 2020, 11, 2572. doi: 10.1038/s41467-020-16477-1
[38]	Huang, M. J.; Ma, J. W.; Zou, Z. L.; Li, H. Y.; Liu, J. Y.; Kong, L. Y.; Pan, Y.; Zhang, W. G.; Liang, Y.; Wang, Y. Chem. Sci. 2022, 13, 11312. doi: 10.1039/D2SC03989C
[39]	Zhang, M.; Lin, J.-H.; Xiao, J.-C. Org. Lett. 2021, 23, 6079. doi: 10.1021/acs.orglett.1c02146
[40]	Wang, Z.; Lin, J. H.; Xiao, J. C. Org. Lett. 2024, 26, 1980. doi: 10.1021/acs.orglett.4c00447
[41]	Yang, B.; Yu, D. H.; Xu, X. H.; Qing, F. L. ACS Catal. 2018, 8, 2839. doi: 10.1021/acscatal.7b03990
[42]	Kuehl, N. J.; Taylor, M. T. J. Am. Chem. Soc. 2023, 145, 22878. doi: 10.1021/jacs.3c08098
[43]	Rustin, G. J.; Agarwal, V.; Dalton, P. I.; Jiang, Z. H.; Liu, Z.; Najor, I. G.; Heydari, B.; Heydari, B.; Kuehl, N. J.; Kumirov, V.; Taylor, M. T.; Gustafson, J. L. Org. Lett. 2025, 27, 13504. doi: 10.1021/acs.orglett.5c04296
[44]	Beatty, J. W.; Douglas, J. J.; Cole, K. P.; Stephenson, C. R. Nat. Commun. 2015, 6, 7919. doi: 10.1038/ncomms8919 pmid: 26258541
[45]	Lewis, S. E.; Wilhelmy, B. E.; Leibfarth, F. A. Chem. Sci. 2019, 10, 6270. doi: 10.1039/C9SC01425J
[46]	Qi, X. K.; Zhang, H.; Pan, Z. T.; Liang, R. B.; Zhu, C. M.; Li, J. H.; Tong, Q. X.; Gao, X. W.; Wu, L. Z.; Zhong, J. J. Chem. Commun. 2019, 55, 10848. doi: 10.1039/C9CC04977K
[47]	Ravetz, B. D.; Tay, N. E. S.; Joe, C. L.; Sezen-Edmonds, M.; Schmidt, M. A.; Tan, Y. C.; Janey, J. M.; Eastgate, M. D.; Rovis, T. ACS Cent. Sci. 2020, 6, 2053. doi: 10.1021/acscentsci.0c00948
[48]	McClain, E. J.; Monos, T. M.; Mori, M.; Beatty, J. W.; Stephenson, C. R. J. ACS Catal. 2020, 10, 12636. doi: 10.1021/acscatal.0c03837
[49]	Hu, Q.; Yu, W. L.; Luo, Y. C.; Hu, X. Q.; Xu, P. F. J. Org. Chem. 2022, 87, 1493. doi: 10.1021/acs.joc.1c02889
[50]	Zhang, M.; Chen, J.; Huang, S. J.; Xu, B. P.; Lin, J.; Su, W. P. Chem Catal. 2022, 2, 1793.
[51]	Yin, D. H.; Su, D. Q.; Jin, J. Cell Rep. Phys. Sci. 2020, 1, 100141.
[52]	Ouyang, Y.; Xu, X. H.; Qing, F. L. Angew. Chem., Int. Ed. 2018, 57, 1.
[53]	Ouyang, Y.; Xu, X. H.; Qing, F. L. Angew. Chem., Int. Ed. 2019, 58, 18508. doi: 10.1002/anie.201911323 pmid: 31612551
[54]	Lee, K.; Lee, S.; Kim, N.; Kim, S.; Hong, S. Angew. Chem., Int. Ed. 2020, 59, 13379. doi: 10.1002/anie.v59.32
[55]	Zhang, K.; Rombach, D.; Notel, N. Y.; Jeschke, G.; Katayev, D. Angew. Chem., Int. Ed. 2021, 60, 22487. doi: 10.1002/anie.202109235 pmid: 34289531
[56]	Song, Y.; Zheng, B. H.; Yang, S.; Li, Y. F.; Liu, Q.; Pan, L. Org. Lett. 2023, 25, 2372. doi: 10.1021/acs.orglett.3c00890 pmid: 36971301
[57]	Zou, L. Q.; Zhao, H. Y.; Wang, X. M.; Dong, J.; Yang, C. G.; Sun, W. Q.; Xu, J. B.; Fan, B. M. Eur. J. Org. Chem. 2024, 27, e202400056.
[58]	Yang, Y. Y.; Huang, X. X.; Jin, Y. Chem. Commun. 2025, 61, 1944. doi: 10.1039/D4CC06099G
[59]	Juliá, F. ChemCatChem 2022, 14, e202200916.
[60]	Poznyak, A. L.; Pavlovski, V. I. Angew. Chem., Int. Ed. 1988, 27, 789. doi: 10.1002/anie.v27:6
[61]	Jiang, X. Y.; Lan, Y.; Hao, Y. D.; Jiang, K.; He, J.; Zhu, J.; Jia, S. Q.; Song, J. S.; Li, S. J.; Niu, L. B. Nat. Commun. 2024, 15, 6115. doi: 10.1038/s41467-024-50507-6
[62]	Han, W. R.; Zhao, Z. Y.; Jiang, K.; Lan, Y.; Yu, X. H.; Jiang, X. Y.; Yang, W.; Wei, D. H.; Li, S. J.; Niu, L. B. Chem. Sci. 2024, 15, 19936. doi: 10.1039/D4SC04038D
[63]	Song, Z. H.; Guo, L.; Yang, C.; Xia, W. J. Org. Chem. Front. 2024, 11, 4436. doi: 10.1039/D4QO00707G
[64]	Fernández‐García, S.; Chantzakou, V. O.; Juliá‐Hernández, F. Angew. Chem., Int. Ed. 2023, 63, e202311984.
[65]	Campbell, B. M.; Gordon, J. B.; Raguram, E. R.; Gonzalez, M. I.; Reynolds, K. G.; Nava, M.; Nocera, D. G. Science 2024, 383, 279. doi: 10.1126/science.adk4919 pmid: 38096334

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