Advances in Trifluoromethoxylation Reactions

doi:10.6023/cjoc202604036

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (9): 3559-3577.DOI: 10.6023/cjoc202604036 Previous Articles Next Articles

ACCOUNT

三氟甲氧基化反应研究进展

马占彩, 汤平平^*()

南开大学化学学院元素有机化学全国重点实验室天津 300071

收稿日期:2026-04-23 修回日期:2026-05-25 发布日期:2026-07-14
通讯作者: 汤平平
基金资助:
国家重点研发计划(2025YFA511100); 国家自然科学基金(21925105); 国家自然科学基金(92156001); 教育部基础和交叉学科突破计划(JYB2025XDXM410); 及天津市自然科学基金(24JCZDJC00700); 及天津市自然科学基金(25ZXZSSS00720)

Advances in Trifluoromethoxylation Reactions

Zhancai Ma, Pingping Tang^*()

State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071

Received:2026-04-23 Revised:2026-05-25 Published:2026-07-14
Contact: Pingping Tang
About author:
Dedicated to the 100th anniversary of the birth of Professor Xikui Jiang.
Supported by:
National Key Research and Development Program of China(2025YFA511100); National Natural Science Foundation of China(21925105); National Natural Science Foundation of China(92156001); Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China(JYB2025XDXM410); Natural Science Foundation of Tianjin(24JCZDJC00700); Natural Science Foundation of Tianjin(25ZXZSSS00720)

Fluorinated organic compounds are playing an increasingly vital role in pharmaceuticals, agrochemicals, and materials science. With superior metabolic stability, moderate lipophilicity, and unique electronic effects, the trifluoromethoxy (OCF₃) group is a highly valued structural motif. In recent years, a variety of innovative synthetic strategies have been developed for the efficient construction of OCF₃-containing organic molecules. Tangʼs group has long been dedicated to the development of novel trifluoromethoxylation reagents and methodologies. The recent progress of Tangʼs group in the field of trifluoromethoxylation reactions achieved between 2021 and 2026 is summarized, with a particular focus on the application of these methods in the synthesis of functional molecules.

Key words: trifluoromethoxylation, trifluoromethyl aryl sulfonate (TFMS), bifunctional N-OCF₃ reagent

Cite this article

Zhancai Ma, Pingping Tang. Advances in Trifluoromethoxylation Reactions[J]. Chinese Journal of Organic Chemistry, 2026, 46(9): 3559-3577.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 19

Figure 1. Representative pharmaceutical and agrochemical molecules containing trifluoromethoxy group

Figure 2. Representative trifluoromethoxylating reagents

Scheme 1. Directing-group-assisted aryl C—H trifluoromethoxylation

Scheme 2. Trifluoromethoxylation of aryl halides

Scheme 3. Trifluoromethoxylation of phenols

Scheme 4. Trifluoromethoxylation of diaryliodonium tetrafluoroborates

Scheme 5. Dibromotrifluoromethoxylation of terminal alkynes

Scheme 6. Enantioselective trifluoromethoxylation of propargyl sulfonates

Scheme 7. Enantioselective trifluoromethoxylation of allylic trichloroacetimidates

Scheme 8. Enantioselective hydrotrifluoromethoxylation of aromatic alkenes

Scheme 9. Trifluoromethoxylation of aziridines

Scheme 10. Dearomative trifluoromethoxylation of indoles

Scheme 11. Trifluoromethoxylation of allenylic trichloroacetimidates

Scheme 12. Bromotrifluoromethoxylation of allenes

Scheme 13. Construction of α‑trifluoromethoxy sulfides via Pummerer rearrangement

Scheme 14. syn-Stereoselective trifluoromethoxylation of bicyclo[1.1.0]butanes

Scheme 15. 1,3-Ditrifluoromethoxylation and 1,3-fluorotrifluoromethoxylation of arylcyclopropanes

Scheme 16. Photoredox amido-trifluoromethoxylation of styrenes

Scheme 17. Advances in trifluoromethoxylation reactions (2021~2026)

References 42

[1]	(a) Kalita, S. J.; Qi, J.; Xiao, L.; Saha, D.; Huang, Y. Y.; Shibata, N. Chem. Rev. 2025, 125, 8477. doi: 10.1021/acs.chemrev.5c00177
	(b) Zhang, C.; Yan, K.; Fu, C.; Peng, H.; Hawker, C. J.; Whittaker, A. K. Chem. Rev. 2022, 122, 167. doi: 10.1021/acs.chemrev.1c00632
	(c) Han, J.; Kiss, L.; Mei, H.; Remete, A. M.; Ponikvar-Svet, M.; Sedgwick, D. M.; Roman, R.; Fustero, S.; Moriwaki, H.; Soloshonok, V. A. Chem. Rev. 2021, 121, 4678. doi: 10.1021/acs.chemrev.0c01263
[2]	(a) Leo, A.; Hansch, C.; Elkins, D. Chem. Rev. 1971, 71, 525. doi: 10.1021/cr60274a001
	(b) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165. doi: 10.1021/cr00002a004
[3]	(a) Federsel, D.; Herrmann, A.; Christen, D.; Sander, S.; Willner, H.; Oberhammer, H. J. Mol. Struct. 2001, 567-568, 127. doi: 10.1016/S0022-2860(01)00541-5
	(b) Klocker, J.; Karpfen, A.; Wolschann, P. Chem. Phys. Lett. 2003, 367, 566. doi: 10.1016/S0009-2614(02)01786-4
	(c) Manteau, B.; Genix,, P.; Brelot, L.; Vors, J. P.; Pazenok, S.; Giornal, F.; Leuenberger, C.; Leroux, F. R. Eur. J. Org. Chem. 2010, 2010, 6043. doi: 10.1002/ejoc.v2010:31
[4]	(a) Manteau, B.; Pazenok, S.; Vors, J. P.; Leroux, F. R. J. Fluorine Chem. 2010, 131, 140. doi: 10.1016/j.jfluchem.2009.09.009
	(b) Landelle, G.; Panossian, A.; Leroux, R. F. Curr. Top. Med. Chem. 2014, 14, 941. doi: 10.2174/1568026614666140202210016
	(c) Chen, Y.; Zhang, A. F.; Wang, W. X.; Zhang, Y.; Gao, T. C. Ann. Appl. Biol. 2012, 161, 247. doi: 10.1111/aab.2012.161.issue-3
	(d) Meanwell, N. A. J. Med. Chem. 2018, 61, 5822. doi: 10.1021/acs.jmedchem.7b01788
[5]	(a) Besset, T.; Jubault,, P.; Pannecoucke, X.; Poisson, T. Org. Chem. Front. 2016, 3, 1004. doi: 10.1039/C6QO00164E
	(b) Yagupol'skii, L. M. Dokl. Akad. Nauk SSSR 1955, 105, 100.
	(c) Mathey, F.; Bensoam, J. Tetrahedron Lett. 1973, 25, 2253. doi: 10.1016/S0040-4039(01)80225-2
	(d) Kuroboshi, M.; Kanie, K.; Hiyama, T. Adv. Synth. Catal. 2001, 343, 235. doi: 10.1002/(ISSN)1615-4169
	(e) Shimizu, M.; Hiyama, T. Angew. Chem., Int. Ed. 2005, 44, 214. doi: 10.1002/anie.v44:2
[6]	(a) Si, Y. F.; Tang, P. P. Chin. J. Chem. 2023, 41, 2179. doi: 10.1002/cjoc.v41.17
	(b) Zheng, W.; Liu, F. X.; Zhao, H. Q.; Xu, Y.; Chen, N.; Liu, Y. J. Chin. J. Org. Chem. 2024, 44, 3321 (in Chinese). doi: 10.6023/cjoc202403011
	(郑威, 刘凤雪, 赵红琼, 许颖, 陈宁, 刘颖杰, 有机化学, 2024, 44, 3321.) doi: 10.6023/cjoc202403011
[7]	(a) Noftle, R. E.; Cady, G. H. Inorg. Chem. 1965, 4, 1010. doi: 10.1021/ic50029a019
	(b) Ran, L. Y.; Zhang, C. P. Chin. J. Org. Chem. 2022, 42, 2045 (in Chinese). doi: 10.6023/cjoc202202025
	(冉龙玉, 张成潘, 有机化学, 2022, 42, 2045.) doi: 10.6023/cjoc202202025
[8]	Kolomeitsev, A. A.; Vorobyev, M.; Gillandt, H. Tetrahedron Lett. 2008, 49, 449. doi: 10.1016/j.tetlet.2007.11.105
[9]	Marrec, O.; Billard, T.; Vors, J. P.; Pazenok, S.; Langlois, B. R. Adv. Synth. Catal. 2010, 352, 2831. doi: 10.1002/adsc.v352:16
[10]	Zhang, C. P.; Vicic, D. A. Organometallics 2012, 31, 7812. doi: 10.1021/om3002747
[11]	Chen, S. X.; Huang, Y. J.; Fang, X.; Li, H. L.; Zhang, Z. X.; Hor, T. S. A.; Weng, Z. Q. Dalton Trans. 2015, 44, 19682. doi: 10.1039/C5DT02078F
[12]	(a) Koller, R.; Huchet, Q.; Battaglia,, P.; Welch, J. M.; Togni, A. Chem. Commun. 2009, 5993.
	(b) Guo, S.; Cong, F.; Guo, R.; Wang, L.; Tang, P. P. Nat. Chem. 2017, 9, 546. doi: 10.1038/nchem.2711
[13]	Zhou, M.; Ni, C. F.; Zeng, Y. W.; Hu, J. B. J. Am. Chem. Soc. 2018, 140, 6801. doi: 10.1021/jacs.8b04000 pmid: 29787259
[14]	Chen, D. Q.; Lu, L.; Shen, Q. L. Org. Chem. Front. 2019, 6, 1801. doi: 10.1039/C9QO00278B
[15]	Li, Y.; Yang, Y.; Xin, J. R.; Tang, P. P. Nat. Commun. 2020, 11, 755. doi: 10.1038/s41467-020-14598-1 pmid: 32029731
[16]	Newton, J. J.; Jelier, B. J.; Meanwell, M.; Martin, R. E.; Britton, R.; Friesen, C. M. Org. Lett. 2020, 22, 1785. doi: 10.1021/acs.orglett.0c00099
[17]	Lu, Z. C.; Kumon, T.; Hammond, G. B.; Umemoto, T. Angew. Chem., Int. Ed. 2021, 60, 16171. doi: 10.1002/anie.202104975 pmid: 34010513
[18]	(a) Duran-Camacho, G.; Ferguson, D. M.; Kampf, J. W.; Bland, D. C.; Sanford, M. S. Org. Lett. 2021, 23, 5138. doi: 10.1021/acs.orglett.1c01664
	(b) Bonnefoy, C.; Chefdeville, E.; Panosian, A.; Hanquet, G.; Leroux, F. R.; Toulgoat, F.; Billard, T. Chem.-Eur. J. 2021, 27, 15986. doi: 10.1002/chem.v27.64
[19]	Yuan, W. J.; Tong, C. L.; Xu, X. H.; Qing, F. L. J. Org. Chem. 2023, 88, 4434. doi: 10.1021/acs.joc.2c03031
[20]	Chen, D. Q.; Luo, Y. R.; Lu, L.; Shen, Q. L. Organometallics. 2024, 43, 3132.
[21]	Zhang, K. X.; Zhao, M. X.; Guo, J. X.; Luan, Y. X.; Tang, P. P. CCS Chem. 2026, 8, 1276. doi: 10.31635/ccschem.025.202506759
[22]	Kellogg, K. B.; Cady, G. H. J. Am. Chem. Soc. 1948, 70, 3986. doi: 10.1021/ja01192a006
[23]	(a) Porter, R. S.; Cady, G. H. J. Am. Chem. Soc. 1957, 79, 5628. doi: 10.1021/ja01578a013
	(b) Roberts, H. L. J. Chem. Soc. 1964, 4538.
[24]	(a) Zheng, W. J.; Morales-Rivera, C. A.; Lee, J. W.; Liu, P.; Ngai, M.-Y. Angew. Chem., Int. Ed. 2018, 57, 9645. doi: 10.1002/anie.v57.31
	(b) Zheng, W. J.; Lee, J. W.; Morales-Rivera, C. A.; Liu, P.; Ngai, M.-Y. Angew. Chem., Int. Ed. 2018, 57, 13795. doi: 10.1002/anie.v57.42
[25]	Jelier, B. J.; Tripet, P. F.; Pietrasiak, E.; Franzoni, I.; Jeschke, G.; Togni, A. Angew. Chem., Int. Ed. 2018, 57, 13784. doi: 10.1002/anie.v57.42
[26]	Guo, L.; Fang, R. J.; Liu, Y.; Zhao, Z. B.; Ye, N. C.; Deng, Z. J.; Altaf, M. B.; Tang, P. P. Org. Biomol. Chem. 2025, 23, 9336. doi: 10.1039/D5OB01162K
[27]	Zhou, J. Y.; Chen, L. H.; Miao, Z. A. Li, J. J.; Luan, Y. X.; Chen, L.; Tang, P. P. J. Am. Chem. Soc. 2025, 147, 38979. doi: 10.1021/jacs.5c11167
[28]	Zhou, J. Y.; Li, J. Y.; Su, C. J.; Luan, Y. X.; Huang, Q. Y.; Tang, P. P. J. Am. Chem. Soc. 2026, 148, 8087. doi: 10.1021/jacs.6c00511
[29]	Li, J. J.; Zhao, M. X.; Huang, Q. Y.; Tang, P. P. J. Org. Chem. 2026, 91, 3031. doi: 10.1021/acs.joc.5c03177
[30]	Wang, F.; Guo, Y. C.; Zhang, Y. T.; Tang, P. P. ACS Catal. 2021, 11, 3218. doi: 10.1021/acscatal.1c00090
[31]	Altaf, M. B.; Zhao, M. X.; Guo, L.; Luan, Y. X.; Tang, P. P. J. Org. Chem. 2025, 90, 10748. doi: 10.1021/acs.joc.5c01052
[32]	Altaf, M. B.; Huang, Q. Y.; Tang, P. P. Org. Chem. Front. 2026, 13, 2817. doi: 10.1039/D6QO00025H
[33]	Hou, Y. D.; Zhang, Z.; Sun, X. Y.; Yang, Z.; Luan, Y. X.; Tang, P. P. Angew. Chem., Int. Ed. 2023, 62, e202218919. doi: 10.1002/anie.v62.18
[34]	Wang, L. Y.; Si, Y. F.; Luan, Y. X.; Tang, P. P. CCS Chem. 2024, 6, 1885. doi: 10.31635/ccschem.024.202404011
[35]	Si, Y. F.; Liu, Y. T.; Zhou, F.; Fang, L.; Wu, K.; Luan, Y. X.; Chen, L.; Tang, P. P. Angew. Chem., Int. Ed. 2025, 64, e202501680. doi: 10.1002/anie.v64.24
[36]	Xin, J. R.; Deng, X. Y.; Tang, P. P. Org. Lett. 2022, 24, 881. doi: 10.1021/acs.orglett.1c04226
[37]	Deng, Z. J.; Meng, L. D.; Bing, X.; Niu, S. X.; Zhang, X. F.; Peng, J. Q.; Luan, Y. X.; Chen, L.; Tang, P. P. J. Am. Chem. Soc. 2024, 146, 2325. doi: 10.1021/jacs.3c11653
[38]	Hou, Y. D.; Luo, Y. C.; Tang, P. P. Org. Lett. 2024, 26, 9764. doi: 10.1021/acs.orglett.4c03676
[39]	Liu, R. Hou, Y. D.; Tang, P. P. Org. Chem. Front. 2025, 12, 3960. doi: 10.1039/D4QO02426E
[40]	Zhao, M. X.; Zhou, Z. Y.; Tang, P. P. Org. Biomol. Chem. 2025, 23, 6127. doi: 10.1039/D5OB00673B
[41]	Yang, P. F.; Chen, S. H.; Lu, J. X.; Ning, P. F.; Zhao, W. Q.; Luan, Y. X.; Chen, L.; Xu, X. F.; Tang, P. P. Org. Lett. 2025, 27, 7679. doi: 10.1021/acs.orglett.5c02396
[42]	Zhou, F.; Fang, L.; Si, Y. F.; Huang, Q. Y.; Tang, P. P. Org. Lett. 2026, 28, 224. doi: 10.1021/acs.orglett.5c04608

三氟甲氧基化反应研究进展

Advances in Trifluoromethoxylation Reactions

RichHTML

PDF

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 19

References 42

Related Articles 2

Recommended Articles

Metrics

Comments

[1]	Longyu Ran, Chengpan Zhang. An Overview of the Reactions with Trifluoromethyl Trifluoromethanesulfonate [J]. Chinese Journal of Organic Chemistry, 2022, 42(7): 2045-2054.
[2]	Wang Feng, Tang Pingping. Recent Advances in Trifluoromethoxylation Reactions [J]. Chinese Journal of Organic Chemistry, 2020, 40(7): 1805-1813.