Copper-Catalyzed Three-Component Synthesis of Triazoles Containing Thioether Fragments

doi:10.6023/cjoc202512045

Abstract

A new strategy for the synthesis of triazoles compounds containing thioether fragments is established based on the nucleophilic ring-opening reaction of cyclic sulfonium salts. A variety of triazole compounds could be efficiently obtained through a multi- component reaction of cyclic sulfonium salts, TMSN₃, and alkynes. This strategy has the advantages of mild reaction conditions, operational simplicity, good to excellent yields, and good substrate tolerance, providing a convenient new strategy for the construction of sulfur-containing triazole compounds.

Key words: copper catalysis, triazoles, Click reaction, sulfonium salts, nucleophilic ring-opening reaction

Cite this article

Fengkai Yu, Xianjin Zhu, Zihan Xu, Lingyu Shi, Yongjia Shi, Xufeng Li, Daoshan Yang. Copper-Catalyzed Three-Component Synthesis of Triazoles Containing Thioether Fragments[J]. Chinese Journal of Organic Chemistry, 2026, 46(7): 2825-2834.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 6

References 19

[1]	Akter, M.; Rupa, K.; Anbarasan, P. Chem. Rev. 2022, 122, 13108. doi: 10.1021/acs.chemrev.1c00991
[2]	(a) Mohammed, I. R.; Kummetha, G.; Singh, N.; Sharova, G.; Dang, J.; Stevenson, M.; Rana, T. M. J. Med. Chem. 2016, 59, 7677. doi: 10.1021/acs.jmedchem.6b00247 pmid: 21323313
	(b) De Simone, R.; Chini, M, G.; Bruno, I.; Riccio, R.; Mueller, D.; Werz, O.; Bifulco, G. J. Med. Chem. 2011, 54, 1565. doi: 10.1021/jm101238d pmid: 21323313
[3]	Shakeel, F.; Iqbal, M.; Ezzeldin, E. J. Pharm. Pharmacol. 2016, 68, 772. doi: 10.1111/jphp.12550 pmid: 27018771
[4]	Agrahari, A. K.; Bose, P.; Jaiswal, M. K.; Rajkhowa, S.; Singh, A. S.; Hotha, S.; Mishra, N.; Tiwari, V. K. Chem. Rev. 2021, 121, 7638. doi: 10.1021/acs.chemrev.0c00920 pmid: 34165284
[5]	(a) García-Álvarez, J.; Díez, J.; Gimeno, J. Green Chem. 2010, 12, 2127. doi: 10.1039/c0gc00342e
	(b) Pawar, G. M.; Bantu, B.; Weckesser, J.; Blechert, S.; Wurst, K.; Buchmeiser, M. R. Dalton Trans. 2009, 41, 9043.
	(c) Hatit, M. Z. C.; Reichenbach, L. F.; Tobin, J. M.; Vilela, F.; Burley, G. A.; Watson, A. J. B. Nat. Commun. 2018, 9, 4021. doi: 10.1038/s41467-018-06551-0
	(d) Zhang, C.; Zheng, L.; Yan, Q.; Hu, Q.; Jia, F.; Chen, Y. ChemistrySelect. 2018, 3, 10277. doi: 10.1002/slct.v3.37
[6]	Shen, T.; Huang, X.; Liang, Y.-F.; Jiao, N. Org. Lett. 2015, 17, 6186. doi: 10.1021/acs.orglett.5b03179 pmid: 26646089
[7]	Phanindrudu, M.; Tiwari, D. K.; Aravilli, V. K.; Bhardwaj, K. C.; Sabapathi, G.; Likhar, P. R.; Tiwari, D. K. Eur. J. Org. Chem. 2016, 2016, 4629. doi: 10.1002/ejoc.v2016.27
[8]	(a) Ladomenou, K.; Nikolaou, G.; Charalambidis, A. G.; Coutsolelos, R. Coord. Chem. Rev. 2016, 306, 1. doi: 10.1016/j.ccr.2015.06.002
	(b) Lauria, A.; Delisi, A.; Mingoia, F.; Terenzi, A.; Martorana, A.; Barone, G.; Almerico, A. M. Eur. J. Org. Chem. 2014, 2014, 3289. doi: 10.1002/ejoc.v2014.16
	(c) Pappula, U.; Kalyana, V, P.; Roy, U. K. Tetrahedron 2025, 179, 134629. doi: 10.1016/j.tet.2025.134629
	(d) Anand, A.; Kumar, R.; Maity, J.; Maikhuri, V. K. Synth. Commun. 2023, 53, 345. doi: 10.1080/00397911.2023.2174031
	(e) Cao, S.; Guo, H.; Zhong, Z.; Chen, D.; Song, W.; Liu, Y.; Wan, J.-P. Sci. Adv. 2025, 11, eaea4120. doi: 10.1126/sciadv.aea4120
	(f) Mickles, D. T.; Westlund, C.; Marcum, J. S.; Meek, S. J. Org. Lett. 2025, 27, 13886. doi: 10.1021/acs.orglett.5c04436
	(g) Ye, J.; Li, G.; Wan, C.; Wan, J.-P. Org. Chem. Front. 2026, 13, 106. doi: 10.1039/D5QO01206F
[9]	(a) Hao, J.; Lv, Y.; Tian, S.; Ma, C.; Cui, W.; Yue, H.; Wei, W.; Yi, D. Chin. Chem. Lett. 2024, 35, 109513. doi: 10.1016/j.cclet.2024.109513
	(b) Xu, Z.; Wan, J.; Liu, Y. Chin. J. Org. Chem. 2023, 43, 2425 (in Chinese).
	(徐忠荣, 万结平, 刘云云, 有机化学, 2023, 43, 2425.) doi: 10.6023/cjoc202212035
	(c) Yang, D.; Yan, Q.; Zhu, E.; Lv, J.; He, W.-M. Chin. Chem. Lett. 2022, 33, 1798. doi: 10.1016/j.cclet.2021.09.068
	(d) Xu, H.; Li, X.; Ma, J.; Zuo, J.; Song, X.; Lv, J.; Yang, D. Chin. Chem. Lett. 2023, 34, 108403. doi: 10.1016/j.cclet.2023.108403
	(e) Niu, T.; Liu, J.; Wu, X.; Zhu, C. Chin. J. Chem. 2020, 38, 803. doi: 10.1002/cjoc.v38.8
	(f) Wang, Z.; Gan, L.; Song, Z.; Liu, Y.; Wan, J.-P. Chin. J. Chem. 2024, 42, 3041. doi: 10.1002/cjoc.v42.23
	(g) Wang, D.; Wang, J; Ma, C.; Jiang, Y.; Yu, B. Chin. J. Org. Chem. 2022, 42, 4024 (in Chinese). doi: 10.6023/cjoc202208039
	(王丹凤, 汪瑾, 马春华, 姜玉钦, 於兵, 有机化学, 2022, 42, 4024.) doi: 10.6023/cjoc202208039
	(h) Wang, Z.; Chen, Y.; Zhu, C. Chin. J. Chem. 2025, 43, 437. doi: 10.1002/cjoc.v43.4
	(i) Wu, Y.; Chen, J.-Y.; Ning, J.; Jiang, X.; Deng, J.; Deng, Y.; Xu, R.; He, W.-M. Green Chem. 2021, 23, 3950. doi: 10.1039/D1GC00562F
	(j) Gui, Q.-W.; Wang, B.-B.; Zhu, S.; Li, F.-L.; Zhu, M.-X.; Yi, M.; Yu, J.-L.; Wu, Z.-L.; He, W.-M. Green Chem. 2021, 23, 4430. doi: 10.1039/D1GC01017D
	(k) Wen, Y.-C.; Hou, J.-C.; Zhou, Q.; Wang, S.-H.; Jiang, J.; Yang, Z.; Zhu, H.-T.; Wang, Z.-L.; He, W.-M. Chin. Chem. Lett. 2025, 36, 111795. doi: 10.1016/j.cclet.2025.111795
	(l) Zhang, Y.; Tang, Y.; Zhou, Y.-Y. Chin. J. Org. Chem. 2025, 45, 1 (in Chinese). doi: 10.6023/cjoc202407043
	(张业飞, 唐勇, 周友运, 有机化学, 2025, 45, 1.) doi: 10.6023/cjoc202407043
	(m) Yue, B.; Wu, X.; Zhu, C. Chin. J. Org. Chem. 2022, 42, 458 (in Chinese). doi: 10.6023/cjoc202108027
	(乐柏佟, 吴新鑫, 朱晨, 有机化学, 2022, 42, 458.) doi: 10.6023/cjoc202108027
[10]	(a) Tian, Z.-Y.; Wang, S.-M.; Jia, S.-J.; Song, H.-X. Org. Lett. 2017, 19, 5454. doi: 10.1021/acs.orglett.7b02764 pmid: 34588919
	(b) Nenaidenko, V. G.; Balenkova, E. S. Russ. J. Org. Chem. 2003, 39, 291. doi: 10.1023/A:1025525327399 pmid: 34588919
	(c) Mondal, M.; Chen, S.; Kerrigan, N. J. Mol. 2018, 23, 738. pmid: 34588919
	(d) Kafuta, K.; Rugen, C. J.; Heilmann, T.; Liu, T.; Golz, C.; Alcarazo, M. Eur. J. Org. Chem. 2021, 2021, 4038. doi: 10.1002/ejoc.202100323 pmid: 34588919
	(e) Šiaučiulis, M.; Ahlsten, N.; Pulis, A. P.; Procter, D. J. Angew. Chem., Int. Ed. 2019, 58, 8779. doi: 10.1002/anie.v58.26 pmid: 34588919
	(f) Kaiser, D.; Klose, I.; Oost, R.; Neuhaus, J.; Maulide, N. Chem. Rev. 2019, 119, 8701. doi: 10.1021/acs.chemrev.9b00111 pmid: 34588919
	(g) Berger, F.; Plutschack, M. B.; Riegger, J.; Yu, W.; Speicher, S.; Ho, M.; Frank, N.; Ritter, T. Nature 2019, 567, 223. doi: 10.1038/s41586-019-0982-0 pmid: 34588919
[11]	Srogl, J.; Allred, G D.; Liebeskind, L S. J. Am. Chem. Soc. 1997, 119, 12376. doi: 10.1021/ja9726926
[12]	Chen, H.; Shang, X.; Jiang, N.; Zhou, Q.; Tang, K.-W.; Zhong, L.-J.; Liu, Y. Org. Chem. Front. 2025, 12, 1498. doi: 10.1039/D4QO01740D
[13]	Cui, W.; Li, X.; Guo, G.; Song, X.; Lv, J.; Yang, D. Org. Lett. 2022, 24, 5391. doi: 10.1021/acs.orglett.2c02078
[14]	(a) Humbrías-Martín, J.; Garrido-González, J. J.; Medrano-Uribe, K.; Pelosi, G.; Laze, L.; Dell’Amico, L. ACS Catal. 2025, 15, 6507. doi: 10.1021/acscatal.5c01231 pmid: 40270886
	(b) Jiang, N.; Chen, H.; Liu, Y.; Zhong, L.-J. Chem. Commun. 2025, 61, 11971. doi: 10.1039/D5CC02517F pmid: 40270886
	(c) Zhu, X.; Song, X.; Li, X.; Wang, F.; Lv, J.; Jiang, M.; Yang, D. Adv. Synth. Catal. 2022, 364, 4384. doi: 10.1002/adsc.v364.24 pmid: 40270886
	(d) Cui, W.; Guo, G.; Wang, Y.; Song, X.; Lv, J.; Yang, D. Chem. Commun. 2023, 59, 6367. doi: 10.1039/D3CC01056B pmid: 40270886
	(e) Li, X.; Jiang, M.; Zuo, J.; Song, X.; Lv, J.; Yang, D. Sci. China Chem. 2023, 66, 791. pmid: 40270886
	(f) Zhang, Y.; Bao, Z.-P.; Kuai, C.-S.; Wu, X.-F. J. Catal. 2023, 426, 1. doi: 10.1016/j.jcat.2023.06.039 pmid: 40270886
	(g) Liu, X.; Li, X.; Wang, L.; Shi, Y.; Lv, J.; Yang, D. Org. Chem. Front. 2024, 11, 2195. doi: 10.1039/D3QO02009F pmid: 40270886
	(h) Liu, X.-Q.; Fan, J.-H.; Tang, K.-W.; Zhong, L.-J.; Liu, Y. Adv. Synth. Catal. 2024, 366, 3868. doi: 10.1002/adsc.v366.18 pmid: 40270886
	(i) Liu, X.-Q.; Chen, H.; Fan, J.-H.; Tang, K.-W.; Zhong, L.-J.; Liu, Y. Org. Lett. 2024, 26, 7650. doi: 10.1021/acs.orglett.4c02759 pmid: 40270886
	(j) Zhong, L.-J.; Liu, X.-Q.; Huang, P.-F.; Tang, K.-W.; Zhou, Q.; Liu, Y. J. Org. Chem. 2025, 90, 15880. doi: 10.1021/acs.joc.5c02286 pmid: 40270886
[15]	(a) Zou, L.-H.; Liu, B.; Wang, C.; Shao, Z.; Zhou, J.; Shao, A.; Wen, J. Org. Chem. Front. 2022, 9, 3231. doi: 10.1039/D2QO00434H pmid: 40956070
	(b) Wang, N.; Jia, Y.; Qin, H.; Jiang, Z.-x.; Yang, Z. Org. Lett. 2020, 22, 7378. doi: 10.1021/acs.orglett.0c02747 pmid: 40956070
	(c) He, Y.; Huang, Z.; Ma, J.; Lin, J.; Zhou, Y.-G.; Yu, Z. Adv. Synth. Catal. 2022, 364, 3023. doi: 10.1002/adsc.v364.17 pmid: 40956070
	(d) Zhou, J.; Wang, Z.; Xu, H.; Su, M.; Wen, J. Org. Biomol. Chem. 2024, 22, 2953. doi: 10.1039/D4OB00203B pmid: 40956070
	(e) Wang, Z.; Su, M.; Xu, H.; Zhou, J.; Wen, J. Adv. Synth. Catal. 2024, 366, 2264. doi: 10.1002/adsc.v366.10 pmid: 40956070
	(f) Yang, L.-H.; Chen, L.; Li, B.; Jin, Y.-X.; Liu, Y.; Peng, S.; Xie, L.-Y. Org. Chem. Front. 2024, 11, 5731. doi: 10.1039/D4QO01417K pmid: 40956070
	(g) Yang, L.-H.; Liu, X.-S.; Liu, C.; Wang, S.-Y.; Xie, L.-Y. J. Org. Chem. 2024, 89, 12668. doi: 10.1021/acs.joc.4c01621 pmid: 40956070
	(h) Yang, L.; Shu, J.; Liu, Y.; Jin, Y.-X.; Chen, S. S.; Huang, W.; Xu, X.-Q.; Xie, L.-Y. J. Org. Chem. 2024, 89, 15248. doi: 10.1021/acs.joc.4c02063 pmid: 40956070
	(i) Peng, S.; Tang, L.; Meng, N.-D.; Peng, H.-Y.; Yao, W.-S.; Tang, S.-S.; Yang, L.-H.; Xie, L.-Y. Tetrahedron 2025, 185, 134816. doi: 10.1016/j.tet.2025.134816 pmid: 40956070
	(j) Shu, J.; Huang, W.; Chen, S.-S.; Yang, L.-H.; Xie, L.-Y. Org. Biomol. Chem. 2025, 23, 8392. doi: 10.1039/D5OB00961H pmid: 40956070
	(k) Zheng, S.; Xu, W.; Zhu, L.; Lei, J.; Xiong, B. J. Org. Chem. 2025, 90, 13525. doi: 10.1021/acs.joc.5c01465 pmid: 40956070
	(l) Li, M.; Ma, J.; Wang, L.; Wu, K.; Zhou, Y.-G.; Yu, Z. J. Org. Chem. 2025, 90, 9593. doi: 10.1021/acs.joc.5c01085 pmid: 40956070
[16]	Wang, Z.; Shao, Z.; Wang, C.; Wen, J. J. Org. Chem. 2024, 89, 3084. doi: 10.1021/acs.joc.3c02546
[17]	Qian, C.-W.; Xiang, W.; Gu, M.-Q. Chem. Eur. J. 2025, 31, e202403990. doi: 10.1002/chem.v31.8
[18]	Yang, L.; Yang, Q.-Z.; Shu, J.; Liu, Y.; Jin, Y.-X.; Liu, Q.; Xie, L.-Y. J. Org. Chem. 2025, 90, 8189. doi: 10.1021/acs.joc.5c00562 pmid: 40491381
[19]	(a) Ma, J.; Li, X.; Chen, Y.; Shi, Y.; Song, X.; Lv, J.; Yang, D. Chin. J. Chem. 2024, 42, 1637. doi: 10.1002/cjoc.v42.14
	(b) Li, J.; Chen, C.; Dong, Y.; Lv, J.; Peng, J.-M.; Jiang, Y.-Y.; Yang, D. Chin. Chem. Lett. 2024, 35, 109732. doi: 10.1016/j.cclet.2024.109732
	(c) Li, X.; Li, X.; Cui, W.; Wu, Q.; Wang, L.; Lv, J.; Yang, D. Org. Lett. 2023, 25, 3260. doi: 10.1021/acs.orglett.3c00990
	(d) Wu, Q.; Li, X.; Lv, J.; Shi, Y.; Yang, D. Org. Lett. 2025, 27, 7703. doi: 10.1021/acs.orglett.5c02449
	(e) Feng, K.; Li, X.; Lv, J.; Shi, Y.; Yang, D. Chin. J. Chem. 2025, 43, 3003. doi: 10.1002/cjoc.v43.22
	(f) Guo, G.; Li, X.; Ma, J.; Shi, Y.; Lv, J.; Yang, D. Chin. Chem. Lett. 2024, 26, 110024.
	(g) Ji, S.; Li, X.; Wang, Y.; Zhang, D.; Lv, J.; Shi, Y.; Yang, D. Org. Lett. 2025, 27, 7892. doi: 10.1021/acs.orglett.5c02202
	(h) Wu, Q.; Yang, D. Chin. J. Org. Chem. 2024, 44, 3571 (in Chinese). doi: 10.6023/cjoc202400058
	(吴启龙, 杨道山, 有机化学, 2024, 44, 3571.) doi: 10.6023/cjoc202400058
	(i) Xu, Hao.; Zhang, J.; Zuo, J.; Wang, F.; Lv, J.; Hun, X.; Yang, D. Chin. J. Org. Chem. 2022, 42, 4037 (in Chinese). doi: 10.6023/cjoc202209004
	(徐浩, 张杰, 左峻泽, 王丰晓, 吕健, 混旭, 杨道山, 有机化学, 2022, 42, 4037.) doi: 10.6023/cjoc202209004

Entry	Catalyst	Base	Solvent	T/℃	Yield^b/%
1	CuI	Et₃N	THF	r.t.	25
2	CuI	Na₂CO₃	THF	r.t.	NR
3	CuI	t-BuONa	THF	r.t.	NR
4	CuI	DIPEA	THF	r.t.	15
5	CuI	Triphenylmine	THF	r.t.	NR
6	CuI	Pyrrolidine	THF	r.t.	10
7	CuI	DBU	THF	r.t.	NR
8^c	CuI	Et₃N	Other solvents instead of Et₃N	r.t.	0~20
9	CuI	Et₃N	Et₃N	r.t.	46
10	CuCl	Et₃N	Et₃N	r.t.	36
11	CuOAc	Et₃N	Et₃N	r.t.	37
12	Cu₂O	Et₃N	Et₃N	r.t.	25
13	CuSO₄	Et₃N	Et₃N	r.t.	NR
14	CuSO₄	NaAsc	MeOH	40	NR
15	CuI	Et₃N	Et₃N	0	NR
16	CuI	Et₃N	Et₃N	40	72
17	CuI	Et₃N	Et₃N	60	NR
18 ^d	CuI	Et₃N	Et₃N	40	66
19 ^e	CuI	Et₃N	Et₃N	40	57

Entry	Catalyst	Base	Solvent	T/℃	Yield^b/%
1	CuI	Et₃N	THF	r.t.	25
2	CuI	Na₂CO₃	THF	r.t.	NR
3	CuI	t-BuONa	THF	r.t.	NR
4	CuI	DIPEA	THF	r.t.	15
5	CuI	Triphenylmine	THF	r.t.	NR
6	CuI	Pyrrolidine	THF	r.t.	10
7	CuI	DBU	THF	r.t.	NR
8^c	CuI	Et₃N	Other solvents instead of Et₃N	r.t.	0~20
9	CuI	Et₃N	Et₃N	r.t.	46
10	CuCl	Et₃N	Et₃N	r.t.	36
11	CuOAc	Et₃N	Et₃N	r.t.	37
12	Cu₂O	Et₃N	Et₃N	r.t.	25
13	CuSO₄	Et₃N	Et₃N	r.t.	NR
14	CuSO₄	NaAsc	MeOH	40	NR
15	CuI	Et₃N	Et₃N	0	NR
16	CuI	Et₃N	Et₃N	40	72
17	CuI	Et₃N	Et₃N	60	NR
18 ^d	CuI	Et₃N	Et₃N	40	66
19 ^e	CuI	Et₃N	Et₃N	40	57

铜催化三组分反应合成含硫醚片段的三氮唑类化合物