Tetrabutylammonium Fluoride-Promoted Hydrothiolation of α-(Trifluoromethyl)styrenes with Thiophenols

doi:10.6023/cjoc202512026

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (6): 2346-2357.DOI: 10.6023/cjoc202512026 Previous Articles Next Articles

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四丁基氟化铵促进的α-(三氟甲基)苯乙烯与硫酚的氢硫醇化反应

张美^†, 陈嫚^†, 陈雨, 姚秋丽, 王安俊^*()

遵义医科大学药学院贵州省化学药物创制全省重点实验室贵州遵义 563000

收稿日期:2025-12-19 修回日期:2026-02-14 发布日期:2026-04-20
作者简介:
^† 共同第一作者
基金资助:
遵义市科技计划(遵市科合HZ字[2023]169号); 贵州省科技计划项目(黔科平台人才[2021]1350-005号); 贵州省科学技术厅(黔科合平台人才-CXTD[2022]012)

Tetrabutylammonium Fluoride-Promoted Hydrothiolation of α-(Trifluoromethyl)styrenes with Thiophenols

Mei Zhang, Man Chen, Yu Chen, Qiuli Yao, Anjun Wang^*()

Guizhou Provincial Key Laboratory of Innovation and Manufacturing for Pharmaceuticals, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000

Received:2025-12-19 Revised:2026-02-14 Published:2026-04-20
Contact: * E-mail: zmcwwwaj1976@163.com
About author:
^† These authors contributed equally to this work.
Supported by:
Zunyi City Science and Technology Plan Project (Zun City Kehe HZ character [2023]169); Guizhou Province Science and Technology Plan Project (Guizhou Science Platform talent [2021]1350-005); Science and Technology Department of Guizhou Province (QKHPTRC-CXTD[2022]-012)

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Abstract

The trifluoromethyl and thioether groups are widely employed in the design of drug molecules. A hydrothiolation reaction of α-(trifluoromethyl)styrenes with thiophenols under solvent-free conditions is reported, which is promoted by tetrabutylammonium fluoride [TBAF, 1 mol/L in tetrahydrofuran (THF)]. This strategy features simple operation, mild reaction conditions, excellent functional group tolerance, and high chemoselectivity. The method demonstrates high atom economy, affording the target products in up to 95% yield, thus providing a concise and efficient alternative approach for the synthesis of β-trifluoromethyl thioethers.

Key words: tetrabutylammonium fluoride (TBAF), hydrothiolation reaction, α-(trifluoromethyl) styrene, β-trifluoromethyl thioethers

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Mei Zhang, Man Chen, Yu Chen, Qiuli Yao, Anjun Wang. Tetrabutylammonium Fluoride-Promoted Hydrothiolation of α-(Trifluoromethyl)styrenes with Thiophenols[J]. Chinese Journal of Organic Chemistry, 2026, 46(6): 2346-2357.

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[1]	(a) Shah, P.; Westwell, A. D. J. Enzyme Inhib. Med. Chem. 2007, 22, 527. doi: 10.1080/14756360701425014 pmid: 26751274
	(b) Müller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881. doi: 10.1126/science.1131943 pmid: 26751274
	(c) Kirk, K. L. Org. Process Res. Dev. 2008, 12, 305. doi: 10.1021/op700134j pmid: 26751274
	(d) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320. doi: 10.1039/B610213C pmid: 26751274
	(e) Wang, J.; Sánchez-Roselló, M.; Aceña, J. L.; del Pozo, C.; Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Chem. Rev. 2014, 114, 2432. doi: 10.1021/cr4002879 pmid: 26751274
	(f) Alonso, C.; Martínez de Marigorta, E.; Rubiales, G.; Palacios, F. Chem. Rev. 2015, 115, 1847. doi: 10.1021/cr500368h pmid: 26751274
	(g) Preshlock, S.; Tredwell, M.; Gouverneur, V. Chem. Rev. 2016, 116, 719. doi: 10.1021/acs.chemrev.5b00493 pmid: 26751274
	(h) Johnson, B. M.; Shu, Y.-Z.; Zhuo, X.; Humphreys, W. G. J. Med. Chem. 2020, 63, 6315. doi: 10.1021/acs.jmedchem.9b01877 pmid: 26751274
[2]	(a) Koike, T.; Akita, M. Acc. Chem. Res. 2016, 49, 1937. doi: 10.1021/acs.accounts.6b00268 pmid: 30983333
	(b) Shen, H.; Liu, Z.; Zhang, P.; Tan, X.; Zhang, Z.; Li, C. J. Am. Chem. Soc. 2017, 139, 9843. doi: 10.1021/jacs.7b06044 pmid: 30983333
	(c) Gao, X.; Xiao, Y.-L.; Wan, X.; Zhang, X. Angew. Chem., Int. Ed. 2018, 57, 3187. doi: 10.1002/anie.v57.12 pmid: 30983333
	(d) Kornfilt, D. J. P.; MacMillan, D. W. C. J. Am. Chem. Soc. 2019, 141, 6853. doi: 10.1021/jacs.9b03024 pmid: 30983333
	(e) Bhaskaran, R. P.; Babu, B. P. Adv. Synth. Catal. 2020, 362, 5219. doi: 10.1002/adsc.v362.23 pmid: 30983333
	(f) Barata-Vallejo, S.; Postigo, A. Chem.-Eur. J. 2020, 26, 11065. doi: 10.1002/chem.v26.49 pmid: 30983333
	(g) Kisukuri, C. M.; Fernandes, V. A.; Delgado, J. A. C.; Häring, A. P.; Paixão, M. W.; Waldvogel, S. R. Chem. Rec. 2021, 21, 2502. doi: 10.1002/tcr.v21.9 pmid: 30983333
	(h) Choi, G.; Lee, G. S.; Park, B.; Kim, D.; Hong, S. H. Angew. Chem., Int. Ed. 2021, 60, 5467. doi: 10.1002/anie.v60.10 pmid: 30983333
	(i) Xiao, H.; Zhang, Z.; Fang, Y.; Zhu, L.; Li, C. Chem. Soc. Rev. 2021, 50, 6308. doi: 10.1039/D1CS00200G pmid: 30983333
	(j) Nair, P. P. R.; Philip, M.; Anilkumar, G. Catal. Sci. Technol. 2021, 11, 6317. doi: 10.1039/D1CY01254A pmid: 30983333
	(k) Saranya, P. V.; Anilkumar, G.; Vaishak, T. B.; Soumya, P. K. Catal. Sci. Technol. 2021, 11, 4690. doi: 10.1039/D1CY00499A pmid: 30983333
	(l) Guo, W.; Cheng, L.; Ma, G.; Tong, W.; Wu, F. Org. Lett. 2022, 24, 1796. doi: 10.1021/acs.orglett.2c00148 pmid: 30983333
	(m) Guo, P.; Tao, M.; Xu, W.-W.; Wang, A.-J.; Li, W.; Yao, Q.; Tong, J.; He, C.-Y. Org. Lett. 2022, 24, 2143. doi: 10.1021/acs.orglett.2c00425 pmid: 30983333
	(n) Guo, P.; Pu, G.; Wang, G.; Zeng, L.-Y.; Li, W.-P.; Li, X.; Zhou, P.-P.; He, C.-Y. Org. Lett. 2024, 26, 3097. doi: 10.1021/acs.orglett.4c00717 pmid: 30983333
	(o) Zhao, W.-W.; Zhang, Y.; Li, X.; Wang, L.; Liu, S.; Chen, J.; He, Y.; Xu, T. Angew. Chem., Int. Ed. 2024, 63, e202318887. pmid: 30983333
	(p) Liu, L.-J.; Tian, M.-Y.; Lang, Z.-Y.; Wang, Y.-L.; He, C.-Y.; Chen, Y.-Z.; Han, W.-Y. Angew. Chem., Int. Ed. 2025, 64, e202501966. pmid: 30983333
	(q) Tian, M.-Y.; Shao, Y.-C.; Zhao, W.-W.; Lang, Z.-Y.; Zhao, J.-F.; Lu, Y.-J.; He, C.-Y.; Chen, Y.-Z.; Han, W.-Y. Sci. China Chem. 2025, 68, 5754. doi: 10.1007/s11426-025-2728-6 pmid: 30983333
	(r) Zhang, H.; Xiao, L.; Guo, H.; Pu, G.; Zhang, Y.; Liang, J.; Wang, P.; Yao, Q.; He, C.-Y. Org. Lett. 2025, 27, 13655. doi: 10.1021/acs.orglett.5c04618 pmid: 30983333
[3]	(a) Jacob, C. Nat. Prod. Rep. 2006, 23, 851. doi: 10.1039/b609523m
	(b) Clayden, J.; MacLellan, P. Beilstein J. Org. Chem. 2011, 7, 582. doi: 10.3762/bjoc.7.68
	(c) Scott, K. A.; Njardarson, J. T. Top. Curr. Chem. 2018, 376, 5.
	(d) Wang, N.; Saidhareddy, P.; Jiang, X. Nat. Prod. Rep. 2020, 37, 246. doi: 10.1039/C8NP00093J
	(e) Hai, Y.; Wei, M.-Y.; Wang, C.-Y.; Gu, Y.-C.; Shao, C.-L. Mar. Life Sci. Technol. 2021, 3, 488. doi: 10.1007/s42995-021-00101-2
	(f) Yang, B.; Yang, Z.-D.; Ma, K.-Z.; Guo, W.-L.; Zhang, T.-H.; Zhao, T.-K. Phytochemistry 2023, 209, 113613. doi: 10.1016/j.phytochem.2023.113613
	(g) Chen, X.; Li, B. Curr. Opin. Chem. Biol. 2023, 76, 102377. doi: 10.1016/j.cbpa.2023.102377
[4]	Dakhama, A.; Gelfand, E. W.; Han, J.; Jia, Y.; Takeda, K.; Shiraishi, Y.; Okamoto, M. Am. J. Respir. Crit. Care Med. 2010, 182, 455. doi: 10.1164/rccm.200912-1811OC
[5]	Mor-Ochomogo, M.; Lohans, C. T. M. J. RSC Med. Chem. 2021, 12, 1623. doi: 10.1039/D1MD00200G
[6]	(a) Qin, F.; Wang, Q.; Zhang, C.; Fang, C.; Zhang, L.; Chen, H.; Zhang, M.; Cheng, F. Infect. Drug Resist. 2018, 11, 1893. doi: 10.2147/IDR pmid: 29846682
	(b) Hacioglu, M.; Guzel, C. B.; Savage, P. B.; Tan, A. S. B. Med. Mycol. 2019, 57, 291. doi: 10.1093/mmy/myy023 pmid: 29846682
[7]	Vela, P.; Llama, E.; Santos, A.; Ochoa, B. Tetrahedron 2005, 61, 6580. doi: 10.1016/j.tet.2005.04.048
[8]	(a) Aruoma, O. I.; Halliwell, B.; Hoey, B. M.; Butler, J. Redox Rep. 2004, 9, 167. doi: 10.1179/135100004225005174 pmid: 26200936
	(b) Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly, D. J.; Meanwell, N. A. J. Med. Chem. 2015, 58, 8315. doi: 10.1021/acs.jmedchem.5b00258 pmid: 26200936
[9]	(a) Feng, M.; Tang, B.; Liang, S. H.; Jiang, X. Curr. Top. Med. Chem. 2016, 16, 1200. doi: 10.2174/1568026615666150915111741 pmid: 25117183
	(b) Johansson, S.; Read, J.; Oliver, S.; Steinberg, M.; Li, Y.; Lisbon, E.; Mathews, D.; Leese, P. T.; Martin, P. Clin. Pharmacokinet. 2014, 53, 837. doi: 10.1007/s40262-014-0161-2 pmid: 25117183
[10]	(a) Robinson, D. J.; Davies, L.; McGuire, N.; Khouzam, M.; Brunner, P. Chem. Chem. Phys. 2000, 2, 1523. doi: 10.1039/a907605k pmid: 31675240
	(b) Dong, H. K.; Kim, A. L.; Lee, J. Org. Lett. 2018, 20, 764. doi: 10.1021/acs.orglett.7b03901 pmid: 31675240
	(c) Kupwade, R. V.; Patil, S. B.; Ramesh, S.; Sharma, A.; Yadav, A.; Mehra, R.; Sharma, S.; Pandey, A.; Singh, R.; Gupta, P. J. Chem. Rev. 2019, 1, 99. doi: 10.33945/SAMI/JCR pmid: 31675240
	(d) Cheng, Z.; Liu, X.; Zhang, H.; Wang, L.; Zhang, Y.; Wang, Z.; Zeng, X. Org. Lett. 2019, 21, 8925. doi: 10.1021/acs.orglett.9b03192 pmid: 31675240
	(e) Cetina-Mancilla, E.; Pérez, J. A.; González, D.; Rodríguez, P.; López, M. A.; Sánchez, R. Eur. Polym. J. 2023, 184, 111800. doi: 10.1016/j.eurpolymj.2022.111800 pmid: 31675240
	(f) Wu, X.; Hou, G.; Zhang, J.; Li, Y.; Wang, Z.; Chen, L.; Yang, H. Org. Lett. 2024, 26, 5917. doi: 10.1021/acs.orglett.4c01808 pmid: 31675240
	(g) Xiang, M.; Zhang, T.; Li, W.; Ding, Y.; Chen, J.; Hu, C.; Yan, Z.; Xu, Z. J. Catal. 2025, 442, 115905. doi: 10.1016/j.jcat.2024.115905 pmid: 31675240
[11]	(a) Feng, X.-T.; Ren, J.-X.; Gao, X.; Min, Q.-Q.; Zhang, X. Angew. Chem., Int. Ed. 2022, 61, e202210103.
	(b) Gao, X.; Ren, X.; Deng, W.; Zhang, X. Chin. J. Chem. 2023, 41, 3521. doi: 10.1002/cjoc.v41.24
	(c) Feng, X.-T.; Min, Q.-Q.; Zeng, X.; Zhao, H.-Y.; Zhang, X. ACS Catal. 2024, 14, 5879. doi: 10.1021/acscatal.4c00281
	(d) Ren, J.-X.; Zhou, M.; Feng, X.-T.; Zhao, H.-Y.; Fu, X.-P.; Zhang, X. Chem. Sci. 2024 15, 10002. doi: 10.1039/D4SC02681K
	(e) Qu, M.-X.; Zhang, J.; Zhao, H.-Y.; Zhang, X. Eur. J. Org. Chem. 2025, 28, 2500625.
	(f) Deng, W.; Geng, S.; Zhao, H.-Y.; Zhang, X. ACS Catal. 2025, 15, 14627. doi: 10.1021/acscatal.5c04127
	(g) Feng, X.-T.; Min, Q.-Q.; Zhang, S.-Y.; Zhao, H.-Y.; Zhang, X. Chem. Sci. 2025, 16, 16552. doi: 10.1039/D5SC05409E
[12]	Yang, Y.-Z.; Lv, G.-F.; Hu, M.; Li, Y.; Li, J.-H. Chin. Chem. Lett. 2023, 34, 108590. doi: 10.1016/j.cclet.2023.108590
[13]	Hang, Z.; Xu, T.; Ju, C.; Gao, C.; Loh, T.-P.; Xie, P. Green Synth. Catal. 2025, 10.1016/j.gresc.2025.03.002.
[14]	Li, L.; Yang, G.; Xiong, T.; Duan, T.; Wang, J.; Wang, X. Chin. Chem. Lett. 2025, 36, 111374. doi: 10.1016/j.cclet.2025.111374
[15]	Lu, W.; Li, W.; Zhou, Y.; Xie, Y.; Chen, W. Chin. Chem. Lett. 2022, 33, 4865. doi: 10.1016/j.cclet.2022.02.061
[16]	(a) Pu, G.; Song, S.-Y.; Yang, J.; Guo, P.; Jia, J.; Liu, P.; Li, X.; Liu, P.; He, C.-Y. Org. Chem. Front. 2024, 11, 3320. doi: 10.1039/D4QO00484A pmid: 39902849
	(b) Chen, M.; Wang, C.; Xie, L.; Mao, T.; Xiao, L.; Wang, Z.; Han, W.-Y.; Liu, P.; Jia, J. Org. Biomol. Chem. 2025, 23, 2445. doi: 10.1039/d4ob01950d pmid: 39902849
[17]	Deng, Y.; Huang, J.; Qian, Y.; Sun, Z.; Huang, Q.; Cao, S. Chem. Asian J. 2024, 19, e202400698.
[18]	Huang, M.-Z.; Xiao, L.-X.; Zhang, X.-G.; Song, X.-F.; Tu, H.-Y. Org. Lett. 2025, 27, 7137. doi: 10.1021/acs.orglett.5c02053
[19]	Zeng, Q.; Liu, Y.; He, J.; Deng, Y.; Zheng, P.; Sun, Z.; Cao, S. Org. Biomol. Chem. 2023, 21, 4982. doi: 10.1039/D3OB00681F
[20]	Zhu, X.; Xie, Z.; Chen, X.; Mu, M.; Wu, H.; Sun, M.; Yang, J.; Wang, L.; Wang, Z. J. Org. Chem. 2024, 89, 14940. doi: 10.1021/acs.joc.4c01684

四丁基氟化铵促进的α-(三氟甲基)苯乙烯与硫酚的氢硫醇化反应

Tetrabutylammonium Fluoride-Promoted Hydrothiolation of α-(Trifluoromethyl)styrenes with Thiophenols

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Entry	Base (x equiv.)	Time/h	Atmosphere	Yield/%
1	K₂CO₃ (0.5)	12	Ar	—
2	Et₃N (0.5)	12	Ar	—
3	KF (0.5)	12	Ar	—
4	CsF ( 0.5)	12	Ar	—
5	TMAF (0.5)	12	Ar	Trace
6^c	TBAF•3H₂O (0.5)	12	Ar	90
7	TBAF•3H₂O (0.5)	12	Ar	91
8	TBAF (0.5)	12	Ar	95 (91)
9	DBN (0.5)	12	Ar	89
10	DBU (0.5)	12	Ar	92
11	TBAF (1.0 )	12	Ar	86
12	TBAF (0.4)	12	Ar	90
13	TBAF (0.3)	12	Ar	91
14	TBAF (0.2)	12	Ar	89
15	TBAF (0.1)	12	Ar	45
16	—	12	Ar	—
17	TBAF (0.5)	10	Ar	79
18	TBAF (0.5)	12	Air	61