Trifluoromethyl Radical-Mediated C(sp3)—H Alkylation Enabled by Photoinduced Thioxanthone Catalysis

doi:10.6023/cjoc202512043

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (4): 1722-1729.DOI: 10.6023/cjoc202512043 Previous Articles Next Articles

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光诱导噻吨酮催化三氟甲基自由基介导的C(sp³)—H键的烷基化

李东生^†, 郑淏文^†, 邓红平^*()

南京农业大学理学院南京 210095

收稿日期:2025-12-28 修回日期:2026-02-10 发布日期:2026-03-13
通讯作者: 邓红平
作者简介:
^†共同第一作者.
基金资助:
国家自然科学基金(21901121)

Trifluoromethyl Radical-Mediated C(sp³)—H Alkylation Enabled by Photoinduced Thioxanthone Catalysis

Dongsheng Li, Haowen Zheng, Hongping Deng^*()

College of Sciences, Nanjing Agricultural University, Nanjing 210095

Received:2025-12-28 Revised:2026-02-10 Published:2026-03-13
Contact: Hongping Deng
About author:
^†These authors contributed equally to this work.
Supported by:
National Natural Science Foundation of China(21901121)

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Abstract

The trifluoromethyl radical is a well-established intermediate in trifluoromethylation reactions. It can also, however, act as a hydrogen atom transfer (HAT) reagent, a property that remains limited studies. A photoinduced, thioxanthone-catalyzed method for the trifluoromethyl radical-mediated C(sp³)—H alkylation was developed. This protocol offers step economy, mild reaction conditions, and operates without stoichiometric external oxidants. Utilizing readily available C(sp³)—H feedstocks, a wide range of acetophenone derivatives were synthesized efficiently. Mechanistic investigations suggest that the reaction proceeds through an energy transfer pathway, sustaining a radical chain mechanism.

Key words: trifluoromethyl radical, thioxantone, C(sp³)—H alkylation, arylvinyl trifluoromethanesulfonate, energy transfer

Cite this article

Dongsheng Li, Haowen Zheng, Hongping Deng. Trifluoromethyl Radical-Mediated C(sp³)—H Alkylation Enabled by Photoinduced Thioxanthone Catalysis[J]. Chinese Journal of Organic Chemistry, 2026, 46(4): 1722-1729.

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References 16

[1]	(a) Böhm, H.-J.; Banner, D.; Bendels, S.; Kansy, M.; Kuhn, B.; Müller, K.; Obst-Sander, U.; Stahl, M. ChemBioChem 2004, 5, 637.
	(b) Hagmann, W. K. J. Med. Chem. 2008, 51, 4359.
	(c) Novás, M.; Matos, M. J. Molecules 2025, 30, 3009.
[2]	(a) Merino, E.; Nevado, C. Chem. Soc. Rev. 2014, 43, 6598.
	(b) Charpentier, J.; Früh, N.; Togni, A. Chem. Rev. 2015, 115, 650.
	(c) Yang, X.; Wu, T.; Phipps, R. J.; Toste, F. D. Chem. Rev. 2015, 115, 826.
	(d) Alonso, C.; de Marigorta, E. M.; Rubiales, G.; Palacios, F. Chem. Rev. 2015, 115, 1847.
	(e) Mandal, D.; Maji, S.; Pal, T.; Sinha, S. K.; Maiti, D. Chem. Commun. 2022, 58, 10442.
	(f) Wang, M.; Xi, W.; Wu, H.; Bai, D. Chin. J. Org. Chem. 2025, 45, 516 (in Chinese).
	(王曼曼, 习文慧, 吴昊, 白大昌, 有机化学, 2025, 45, 516.)
	(g) Huang, G.; Xue, X.-S. Acta Chim. Sinica 2024, 82, 132 (in Chinese).
	(黄广龙, 薛小松, 化学学报, 2024, 82, 132.)
	(h) Li, S.; Lu, J.; Liu, J.; Jiang, L.; Yi, W. Acta Chim. Sinica 2024, 82, 110 (in Chinese).
	(李珊, 路俊欣, 刘杰, 蒋绿齐, 易文斌, 化学学报, 2024, 82, 110.)
[3]	(a) Studer, A. Angew. Chem., Int. Ed. 2012, 51, 8950.
	(b) Wang, X.; Zhang, Y.; Wang, J. Sci. Sin. Chim. 2012, 42, 1417.
	(c) Koike, T.; Akita, M. Top. Catal. 2014, 57, 967.
	(d) Xiao, H.; Zhang, Z.; Fang, Y.; Zhu, L.; Li, C. Chem. Soc. Rev. 2021, 50, 6308.
	(e) Lin, D.; Coe, M.; Krishnamurti, V.; Ispizua-Rodriguez, X.; Prakash, G. K. S. Chem. Rec. 2023, 23, e202300104.
	(f) Zhang, L.; Li, Y.; Huang, D.; Wu, J. Asian J. Org. Chem. 2025, 14, e00550.
[4]	(a) Wang, D.; Mück-Lichtenfeld, W.; Studer, A. J. Am. Chem. Soc. 2019, 141, 14126.
	(b) Wang, D.; Mück-Lichtenfeld, W.; Studer, A. J. Am. Chem. Soc. 2020, 142, 9119.
[5]	(a) Cao, H.; Tang, X.; Tang, H.; Yuan, Y.; Wu, J. Chem. Catal. 2021, 1, 523.
	(b) Capaldo, L.; Ravelli, D.; Fagnoni, M. Chem. Rev. 2022, 122, 1875.
[6]	(a) Stompor, M.; Dancewicz, K.; Gabryś B.; Anioł M. J. Agric. Food Chem. 2015, 63, 6749.
	(b) Miller, D. K.; Lever, J. R.; Rodvelt, K. R.; Baskett, J. A.; Will, M. J.; Kracke, G. R. Drug Alcohol Depend. 2007, 89, 282.
	(c) Kudo, S.; Ishizaki, T. Clin. Pharmacokinet. 1999, 37, 435.
[7]	(a) Ji, J.; Liu, P.; Sun, P. Chem. Commun. 2015, 51, 7546.
	(b) Hua, Z.; Tang, Y.; Zhang, S.; Li, X.; Du, X.; Xu, X. Synlett 2015, 26, 2557.
	(c) Ji, P.-Y.; Liu, Y.-F.; Xu, J.-W.; Luo, W.-P.; Liu, Q.; Guo, C.-C. J. Org. Chem. 2017, 82, 2965.
	(d) Li, J.; Li, J.; Yuan, S.; Zhang, Q.; Li, D. Asian J. Org. Chem. 2019, 8, 1842.
	(e) Mou, D.; Li, Q.; Du, Z. ChemistrySelect 2023, 8, e202203486.
	(f) Das, K. M.; Pal, A.; Surya T, L.; Roy, L.; Thakur, A. Chem.-Eur. J. 2024, 30, e202303776.
[8]	Lee, J. Y.; Lim, K.-C.; Meng, X.; Kim, S. Synlett 2010, 11, 1647.
[9]	(a) Li, D.-S.; Liu, T.; Hong, Y.; Cao, C.-L.; Wu, J.; Deng, H.-P. ACS Catal. 2022, 12, 4473.
	(b) Dong, M.-Y.; Han, C.-Y.; Li, D.-S.; Hong, Y.; Liu, F.; Deng, H.-P. ACS Catal. 2022, 12, 9533.
	(c) Cao, C.-L.; Zhang, G.-X.; Xue, F.; Deng, H.-P. Org. Chem. Front. 2022, 9, 959.
	(d) Hong, Y.; Dong, M.-Y.; Li, D.-S.; Deng, H.-P. Org. Lett. 2022, 24, 7677.
	(e) Chen, P.-F.; Li, D.-S.; Ou, W.-T.; Xue, F.; Deng, H.-P. Org. Lett. 2023, 25, 6184.
	(f) Zhang, G.-X.; Li, D.-S.; Chen, A.-F.; Xue, F.; Deng, H.-P. Adv. Synth. Catal. 2023, 365, 4604.
	(g) Hong, Y.; Deng, H.-P. ChemPhotoChem 2024, 9, e202400282.
	(h) Hong, Y.; Deng, H.-P. Chin. J. Org. Chem. 2025, 45, 1569 (in Chinese).
	(洪洋, 邓红平, 有机化学, 2025, 45, 1569.)
	(i) Li, D.-S.; Zhang, G.-X.; Qian, H.; Xue, F.; Deng, H.-P. Adv. Synth. Catal. 2025, 367, e202500314.
[10]	(a) Liu, S.; Jie, J.; Yu, J.; Yang, X. Adv. Synth. Catal. 2018, 360, 267.
	(b) Wang, H.; Bellotti, P.; Zhang, X.; Paulisch, T. O.; Glorius, F. Chem 2021, 7, 3412.
	(c) Feng, Q.; Fu, Y.; Zheng, Y.; Liao, S.; Huang, S. Org. Lett. 2022, 24, 3702.
	(d) Xiang, P.; Sun, K.; Shi, A.; An, J.; Chen, X.; Qu, L.; Yu, B. Green Chem. 2025, 27, 1820.
[11]	Liu, Z.; Long, J.; Xiao, X.; Lin, J.-H.; Zheng, X.; Xiao, J.-C.; Cao, Y.-C. Chin. Chem. Lett. 2019, 30, 714.
[12]	(a) Tan, Y.; Wu, X.; Han, Y.-P.; Zhang, Y.; Zhang, H.-Y.; Zhao, J. J. Org. Chem. 2022, 87, 8551.
	(b) Zhang, D.-L.; Le, Z.-G.; Li, Q.; Xie, Z.-B.; Yang, W.-W.; Zhu, Z.-Q. Chem. Commun. 2024, 60, 2958.
	(c) Huang, X.-L.; Zhang, D.-L.; Li, Q.; Xie, Z.-B.; Le, Z.-G.; Zhu, Z.-Q. Org. Lett. 2024, 26, 3727.
[13]	(a) Zhou, Q.-Q.; Zou, Y.-Q.; Lu, L.-Q.; Xiao, W.-J. Angew. Chem., Int. Ed. 2019, 58, 1586.
	(b) Strieth-Kalthoff, F.; Glorius, F. Chem 2020, 6, 1888.
	(c) Großkopf, J.; Kratz, T.; Rigotti, T.; Bach, T. Chem. Rev. 2022, 122, 1626.
[14]	(a) Roberts, B. P. Chem. Soc. Rev. 1999, 28, 25.
	(b) Garwood, J. J. A.; Chen, A. D.; Nagib, D. A. J. Am. Chem. Soc. 2024, 146, 28034.
[15]	Kawamoto, T.; Hisayuki, M.; Kamimura, A. Chem. Lett. 2024, 53, upae072.
[16]	(a) Zhu, K.; Ohtani, T.; Tripathi, C. B.; Uraguchi, D.; Ooi, T. Chem. Lett. 2019, 48, 715.
	(b) Raviola, C.; Ravelli, D. Synlett 2019, 30, 803.
	(c) Grover, J.; Prakash, G.; Teja, C.; Lahiri, G. K.; Maiti, D. Green Chem. 2023, 25, 3431.

Entry	Photocatalyst	Base (x/equiv.)	Solvent	Yield^a/%
1	PC1	KOH (2.5)	THF	74
2	PC2	KOH (2.5)	THF	0
3	PC3	KOH (2.5)	THF	82
4	PC3	NaOH (2.5)	THF	0
5	PC3	K₂CO₃(2.5)	THF	10
6	PC3	KOAc 2.5)	THF	10
7	PC3	KOH (2.0)	THF	78
8	PC3	KOH (3.0)	THF	82
9^b	PC3	KOH (2.5)	THF	87
10^b^,^c	PC3	KOH (2.5)	EA	80
11^b^,^c	PC3	KOH (2.5)	MeCN	0
12^b^,^c	PC3	KOH (2.5)	DCM	0
13^b^,^d	PC3	KOH (2.5)	THF	70
14^b	PC3	—	THF	0
15^b^,^e	PC3	KOH (2.5)	THF	0
16^b	—	KOH (2.5)	THF	0
17^b^,^f	—	KOH (2.5)	THF	50

Entry	Photocatalyst	Base (x/equiv.)	Solvent	Yield^a/%
1	PC1	KOH (2.5)	THF	74
2	PC2	KOH (2.5)	THF	0
3	PC3	KOH (2.5)	THF	82
4	PC3	NaOH (2.5)	THF	0
5	PC3	K₂CO₃(2.5)	THF	10
6	PC3	KOAc 2.5)	THF	10
7	PC3	KOH (2.0)	THF	78
8	PC3	KOH (3.0)	THF	82
9^b	PC3	KOH (2.5)	THF	87
10^b^,^c	PC3	KOH (2.5)	EA	80
11^b^,^c	PC3	KOH (2.5)	MeCN	0
12^b^,^c	PC3	KOH (2.5)	DCM	0
13^b^,^d	PC3	KOH (2.5)	THF	70
14^b	PC3	—	THF	0
15^b^,^e	PC3	KOH (2.5)	THF	0
16^b	—	KOH (2.5)	THF	0
17^b^,^f	—	KOH (2.5)	THF	50

光诱导噻吨酮催化三氟甲基自由基介导的C(sp³)—H键的烷基化

Trifluoromethyl Radical-Mediated C(sp³)—H Alkylation Enabled by Photoinduced Thioxanthone Catalysis

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光诱导噻吨酮催化三氟甲基自由基介导的C(sp3)—H键的烷基化