REVIEW

Advances in Trifluoromethoxylation Reactions

  • Ma Zhancai ,
  • Tang Pingping
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  • aState Key Laboratory and Institute of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300071

Received date: 2026-04-23

  Revised date: 2026-05-25

  Online published: 2026-07-14

Supported by

National Key Research and Development Program of China (No. 2025YFA151110), the NFSC (21925105 and 92156001), Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China (JYB2025XDXM410), the Natural Science Foundation of Tianjin (grant no. 24JCZDJC00700, 25ZXZSSS00720).

Abstract

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. Our research group has long been dedicated to the development of novel trifluoromethoxylation reagents and methodologies. This review summarizes our recent progress in the field of trifluoromethoxylation reactions achieved between 2021 and 2026, with a particular focus on the application of these methods in the synthesis of functional molecules.

Cite this article

Ma Zhancai , Tang Pingping . Advances in Trifluoromethoxylation Reactions[J]. Chinese Journal of Organic Chemistry, 0 : 202604036 -202604036 . DOI: 10.6023/cjoc202604036

References

[1] (a) Kalita S. J.; Qi J.; Xiao L.; Saha D.; Huang Y. Y.; Shibata N. Chem. Rev. 2025, 125, 8477-8654.
(b) Zhang C.; Yan K.; Fu C.; Peng H.; Hawker C. J.; Whittaker, A. K. Chem Rev. 2022, 122, 167-208.
(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, 4678-4742.
[2] (a) Leo, A.; Hansch, C.; Elkins, D.Chem. Rev. 1971, 71, 525-616.
(b) Hansch C.; Leo A.; Taft, R. W. Chem. Rev. 1991, 91, 165-195.
[3] (a) Federsel D.; Herrmann A.; Christen D.; Sander S.; Willner H.; Oberhammer, H. J. Mol. Struct. 2001, 567-568, 127-136.
(b) Klocker J.; Karpfen A.; Wolschann, P. Chem. Phys. Lett. 2003, 367, 566-575.
(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, 6043-6066.
[4] (a) Manteau, B.; Pazenok, S.; Vors, J. P.; Leroux, F. R.J. Fluorine Chem. 2010, 131, 140-158.
(b) Landelle, G.; Panossian, A.; Leroux, R. F.Curr. Top. Med. Chem. 2014, 14, 941-951.
(c) Chen Y.; Zhang A. F.; Wang W. X.; Zhang Y.; Gao, T. C. Ann. Appl. Biol. 2012, 161, 247-254.
(d) Meanwell, N. A. J. Med. Chem. 2018, 61, 5822-5880.
[5] (a) Besset T.; Jubault P.; Pannecoucke X.; Poisson, T. Org. Chem. Front. 2016, 3, 1004-1010.
(b) Yagupol'skii, L. M. Dokl. Akad. Nauk. SSSR. 1955, 105, 100-102.
(c) Mathey F.; Bensoam J.; Tetrahedron Lett. 1973, 25, 2253-2256.
(d) Kuroboshi M.; Kanie K.; Hiyama, T. Adv. Synth. Catal. 2001, 343, 235-250.
(e) Shimizu M.; Hiyama, T. Angew. Chem., Int. Ed. 2005, 44, 214-231.
[6] (a) Si, Y. F.; Tang, P. P. Chin. J. Chem. 2023, 41, 2179-2196.
(b) Zheng W.; Liu F. X.; Zhao H. Q.; Xu Y.; Chen N.; Liu, Y. J. Chin. J. Org. Chem. 2024, 44, 3321-3334.
[7] (a) Noftle, R. E.; Cady, G. H. Inorg. Chem. 1965, 4, 1010-1012.
(b) Ran, L. Y.; Zhang, C. P. Chin. J. Org. Chem. 2022, 42, 2045-2054.
[8] Kolomeitsev A. A.; Vorobyev M.; Gillandt H. Tetrahedron Lett. 2008, 49, 449-454.
[9] Marrec O.; Billard T.; Vors J. P.; Pazenok S.; Langlois, B. R. Adv. Synth. Catal. 2010, 352, 2831-2837.
[10] Zhang C. P.; Vicic D. A. Organometallics. 2012, 31, 7812-7815.
[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, 19682-19686.
[12] (a) Koller, R.; Huchet, Q.; Battaglia, P.; Welch, J. M.; Togni, A.Chem. Commun. 2009, 5993-5995.
(b) Guo S.; Cong F.; Guo R.; Wang L.; Tang, P. P. Nature. Chem. 2017, 9, 546-551.
[13] Zhou M.; Ni C. F.; Zeng Y. W.; Hu, J. B. J. Am. Chem. Soc. 2018, 140, 6801-6805.
[14] Chen D. Q.; Lu L.; Shen, Q. L. Org. Chem. Front. 2019, 6, 1801-1806.
[15] Li Y.; Yang Y.; Xin J. R.; Tang, P. P. Nat. Commun. 2020, 11, 755-761.
[16] Newton J. J.; Jelier B. J.; Meanwell M.; Martin R. E.; Britton R.; Friesen, C. M. Org. Lett. 2020, 22, 1785-1790.
[17] Lu Z. C.; Kumon T.; Hammond G. B.; Umemoto, T. Angew. Chem. Int. Ed. 2021, 60, 16171-16177.
[18] (a) Duran-Camacho, G.; Ferguson, D. M.; Kampf, J. W.; Bland, D. C.; Sanford, M. S.Org. Lett. 2021, 23, 5138-5142.
(b) Bonnefoy, C.; Chefdeville, E.; Panosian, A.; Hanquet, G.; Leroux, F. R.; Toulgoat, F.; Billard, T.Chem. Eur. J. 2021, 27, 15986-15991.
[19] Yuan, W. J.; Tong, C. L.; Xu, X. H.; Qing, F. L.J. Org. Chem. 2023, 88, 4434-4441.
[20] Chen D. Q.; Luo Y. R.; Lu L.; Shen Q. L. Organometallics. 2024, 43, 3132-3136.
[21] Zhang K. X.; Zhao M. X.; Guo J. X.; Luan Y. X.; Tang, P. P. CCS Chem. 2026, 8, 1276-1283.
[22] Kellogg K. B.; Cady, G. H. J. Am. Chem. Soc. 1948, 70, 3986-3990.
[23] (a) Porter R. S.; Cady, G. H. J. Am. Chem. Soc. 1957, 79, 5628-5631.
(b) Roberts, H. L.J. Chem. Soc. 1964, 4538-4540.
[24] (a) Zheng, W. J.; Morales-Rivera, C. A.; Lee, J. W.; Liu, P.; Ngai, M.-Y.Angew. Chem. Int. Ed. 2018, 57, 9645-9649.
(b) Zheng W. J.; Lee J. W.; Morales-Rivera C. A.; Liu P.; Ngai, M.-Y. Angew. Chem. Int. Ed. 2018, 57, 13795-13799.
[25] Jelier B. J.; Tripet P. F.; Pietrasiak E.; Franzoni I.; Jeschke G.; Togni, A. Angew. Chem. Int. Ed. 2018, 57, 13784-13789.
[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, 9336-9340.
[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, 38979-38986.
[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, 8087-8094.
[29] Li J. J.; Zhao M. X.; Huang Q. Y.; Tang, P. P. J. Org. Chem. 2026, 91, 3031-3036.
[30] Wang F.; Guo Y. C.; Zhang Y. T.; Tang, P. P. ACS Catal. 2021, 11, 3218-3223.
[31] Altaf M. B.; Zhao M. X.; Guo L.; Luan Y. X.; Tang, P. P. J. Org. Chem. 2025, 90, 10748-10755.
[32] Altaf, M. B.; Huang, Q. Y.; Tang, P. P.Org. Chem. Front. 2026, 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.
[34] Wang L. Y.; Si Y. F.; Luan Y. X.; Tang, P. P. CCS Chem. 2024, 6, 1885-1894.
[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.
[36] Xin J. R.; Deng X. Y.; Tang, P. P. Org. Lett. 2022, 24, 881-885.
[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, 2325-2332.
[38] Hou, Y. D.; Luo, Y. C.; Tang, P. P.Org. Lett. 2024, 26, 9764-9768.
[39] Liu, R. Hou, Y. D.; Tang, P. P. Org. Chem. Front. 2025, 12, 3960-3964.
[40] Zhao, M. X.; Zhou, Z. Y.; Tang, P. P.Org. Biomol. Chem. 2025, 23, 6127-6132.
[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, 7679-7684.
[42] Zhou F.; Fang L.; Si Y. F.; Huang Q. Y.; Tang, P. P. Org. Lett. 2026, 28, 224-228.
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