Light-Induced Intramolecular Cyclization through Insertion of N-Tosylhydrazone into C(sp3)—H and C=C Bonds

doi:10.6023/cjoc202601024

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (8): 3180-3188.DOI: 10.6023/cjoc202601024 Previous Articles Next Articles

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光促进N-对甲苯磺酰腙的分子内C(sp³)—H/C=C插入环化反应研究

李金瑞^a, 卫可悦^a, 王花^a^,^b^,^*()

^a 第四军医大学(空军军医大学)药学系化学制药学教研室西安 710032
^b 第四军医大学(空军军医大学)军事医学创新中心西安 710032

收稿日期:2026-01-19 修回日期:2026-03-18 发布日期:2026-05-13
通讯作者: 王花
基金资助:
国家自然科学基金(22201303); 陕西省三秦英才引进计划-青年资助项目

Light-Induced Intramolecular Cyclization through Insertion of N-Tosylhydrazone into C(sp³)—H and C=C Bonds

Jinrui Li^a, Keyue Wei^a, Hua Wang^a^,^b^,^*()

^a Department of Chemistry, School of Pharmacy, The Fourth Military Medical University (Air Force Medical University), Xi'an 710032
^b Military Medical Innovation Center, The Fourth Military Medical University (Air Force Medical University), Xi'an 710032

Received:2026-01-19 Revised:2026-03-18 Published:2026-05-13
Contact: Hua Wang
Supported by:
National Natural Science Foundation of China(22201303); Sanqin Talents Introduction Program of Shaanxi Province-Youth Project

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Abstract

A light-promoted, transition-metal-free intramolecular C(sp³)—H/C=C insertion cyclization of N-tosylhydrazones has been developed. Using cesium carbonate as the base, the reaction proceeds under mild conditions via photoexcited hydrazone anions to generate highly reactive alkyl diazo intermediates. This enables highly selective insertion into both intramolecular C(sp³)—H bonds and C=C double bonds, efficiently constructing over 20 differently substituted [4.1.0]-fused bicyclic and benzofuran frameworks with yields up to 85%. The strategy exhibits broad functional group tolerance and scalability to gram-scale. Mechanistic studies indicate that the formation of photoexcited hydrazone anions is the key step in the reaction pathway.

Key words: N-tosylhydrazone, photoexcited anion, insertion into C(sp³)—H bond, insertion into C=C bond, intramolecular cyclization

Cite this article

Jinrui Li, Keyue Wei, Hua Wang. Light-Induced Intramolecular Cyclization through Insertion of N-Tosylhydrazone into C(sp³)—H and C=C Bonds[J]. Chinese Journal of Organic Chemistry, 2026, 46(8): 3180-3188.

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References 12

[1]	(a) Corey, E. J. Angew. Chem., Int. Ed. 2002, 41, 1650.
	(b) Newman, D. J.; Cragg, G. M. J. Nat. Prod. 2016, 79, 62.
	(c) Ebner, C.; Carreira, E. M. Chem. Rev. 2017, 117, 11651.
	(d) Greiner, L.; Pahl, C. A.; Heinzke, A. L. B. J. Med. Chem. 2025, 68, 14137.
[2]	(a) Eftekhari-Sis, B.; Zirak, M. Chem. Rev. 2015, 115, 151.
	(b) Kwiecień H. Prog. Heterocycl. Chem. 2021, 33, 175.
	(c) Zhang, X.; Bi, W.; Cao, Z. Molecules 2024, 29, 5458.
[3]	(a) Xia, Y.; Qiu, D.; Wang, J. Chem. Rev. 2017, 117, 13810.
	(b) He, Y.; Huang, Z.; Wu, K. Chem. Soc. Rev. 2022, 51, 2759.
	(c) D’yakonov, V. A.; Trapeznikova, O. A.; Meijere, A. Chem. Rev. 2014, 114, 5775.
	(d) Liu, Z.; Liu, L. Acta Chim. Sinica 2025, 83, 1025 (in Chinese).
	(刘郅勍, 刘柳, 化学学报, 2025, 83, 1025.)
[4]	(a) Kirmse, W.; Ozkir, I. S. J. Am. Chem. Soc. 1992, 114, 7590.
	(b) Kirmse, W.; Oezkir, I. S.; Schnitzler, D. J. Am. Chem. Soc. 1993, 115, 792.
[5]	(a) Maas, G. Chem. Soc. Rev. 2004, 33, 183.
	(b) Zhu, D.; Chen, L. F.; Fan, H. L. Chem. Soc. Rev. 2020, 49, 908.
	(c) Mato, M.; Franchino, A.; Garcı́a-Morales, C. Chem. Rev. 2021, 121, 8613.
	(d) Pan, Y.; Wang, Y.; Karmakar, S. Org. Chem. Front. 2024, 11, 3777.
	(e) Yang, Z.; Stivanin, M. L.; Jurberg, I. D. Chem. Soc. Rev. 2020, 49, 6833.
[6]	(a) Liu, Z.; Raveendra, K.; Wang, B. F. Org. Chem. Front. 2019, 6, 121.
	(b) Liu, Z.; Cao, S.; Yu, W. Chem 2020, 6, 2110.
	(c) Liu, Z.; Wang, H.; Sivaguru, P. Nat. Commun. 2022, 13, 1674.
[7]	(a) Zhang, Y.; Han, X.; Li, D.; Wang, D. ACS Cent. Sci. 2025, 11, 742.
	(b) Zhang, Y.; Li, Q.; Wang, P. Green Chem. 2024, 26, 4600.
[8]	(a) Hirai, K.; Itoh, T.; Tomioka, H. Chem. Rev. 2009, 109, 3275.
	(b) Zhang, Z.; Gevorgyan, V. Chem. Rev. 2024, 124, 7214.
	(c) Zhang, X.; Sivaguru, P.; Pan, Y. Chem. Rev. 2025, 125, 1049.
	(d) Yang, Y.; Liu, S.; Li, S. Angew. Chem., Int. Ed. 2023, 62, e202214519.
	(e) Xia, D.; Wu, R.; Wang, J.; Han, X. ACS Catal. 2023, 13, 9806.
	(f) George, V.; König, B. Chem. Commun. 2023, 59, 11835.
	(g) Li, Q.; Wang, D.; Wang, J. Sci China:Chem, 2025, 68: 1937.
[9]	(a) Wang, H.; Wang, S.; George, V. Angew. Chem., Int. Ed. 2022, 61, e202211578.
	(b) Pointner, F. L.; Poll, J.; Taskinen, E. K. Chem.-Eur. J. 2025, 3, e202500133.
[10]	Cheung, W.-H.; Zheng, S.-L.; Yu, W.-Y. Org. Lett. 2003, 5, 2535.
[11]	(a) Zhu, Y.; Zhang, J.; Zhang, Y. Chin. Chem. Lett. 2024, 35, 109573.
	(b) Zhao, H.; Zong, Y.; Sun, Y. Org. Lett. 2024, 26, 1739.
	(b) Yang, J.; Zhao, Y.; Shi, L. Chin. J. Org. Chem. 2025, 45, 559 (in Chinese).
	(杨俊峰, 赵艳秋, 时磊, 有机化学, 2025, 45, 559.)
	(d) Xie, R.; Xie, F.; Sun, R. Chin. J. Org. Chem. 2025, 45, 2913 (in Chinese).
	(解人杰, 谢复开, 孙然, 有机化学, 2025, 45, 2913.)
[12]	Taber, D. F.; Guo, P. J. Org. Chem. 2008, 73, 9479.

Entry	Base (Dosage/equiv.)	Solvent (V/mL)	Time/h	Yield^b/%
1	Cs₂CO₃ (3.0)	MeCN (1)	20	35
2	K₂CO₃ (3.0)	MeCN (1)	20	12
3	K₃PO₄ (3.0)	MeCN (1)	20	15
4	Et₃N (3.0)	MeCN (1)	20	Trace
5	DBU (3.0)	MeCN (1)	20	Trace
6	Cs₂CO₃ (3.0)	DMF (1)	20	Trace
7	Cs₂CO₃ (3.0)	THF (1)	20	66
8	Cs₂CO₃ (3.0)	DCM (1)	20	52
9	Cs₂CO₃ (3.0)	EA (1)	20	65
10	Cs₂CO₃ (3.0)	Toluene (1)	20	85
11	Cs₂CO₃ (3.0)	PhCl (1)	20	84
12	Cs₂CO₃ (3.0)	Hexane (1)	20	30
13	Cs₂CO₃ (3.0)	MTBE (1)	20	71
14	Cs₂CO₃ (1.0)	Toluene (1)	20	67
15	Cs₂CO₃ (2.0)	Toluene (1)	20	80
16	Cs₂CO₃ (4.0)	Toluene (1)	20	82
17	Cs₂CO₃ (3.0)	Toluene (2)	20	79
18	Cs₂CO₃ (3.0)	Toluene (0.5)	20	76
19^c	Cs₂CO₃ (3.0)	Toluene (1)	20	60
20^d	Cs₂CO₃ (3.0)	Toluene (1)	30	65
21	Cs₂CO₃ (3.0)	Toluene (1)	12	63
22	Cs₂CO₃ (3.0)	Toluene (1)	30	83
23^e	Cs₂CO₃ (3.0)	Toluene (1)	20	n.d.
24	—	Toluene (1)	30	n.d.

Entry	Base (Dosage/equiv.)	Solvent (V/mL)	Time/h	Yield^b/%
1	Cs₂CO₃ (3.0)	MeCN (1)	20	35
2	K₂CO₃ (3.0)	MeCN (1)	20	12
3	K₃PO₄ (3.0)	MeCN (1)	20	15
4	Et₃N (3.0)	MeCN (1)	20	Trace
5	DBU (3.0)	MeCN (1)	20	Trace
6	Cs₂CO₃ (3.0)	DMF (1)	20	Trace
7	Cs₂CO₃ (3.0)	THF (1)	20	66
8	Cs₂CO₃ (3.0)	DCM (1)	20	52
9	Cs₂CO₃ (3.0)	EA (1)	20	65
10	Cs₂CO₃ (3.0)	Toluene (1)	20	85
11	Cs₂CO₃ (3.0)	PhCl (1)	20	84
12	Cs₂CO₃ (3.0)	Hexane (1)	20	30
13	Cs₂CO₃ (3.0)	MTBE (1)	20	71
14	Cs₂CO₃ (1.0)	Toluene (1)	20	67
15	Cs₂CO₃ (2.0)	Toluene (1)	20	80
16	Cs₂CO₃ (4.0)	Toluene (1)	20	82
17	Cs₂CO₃ (3.0)	Toluene (2)	20	79
18	Cs₂CO₃ (3.0)	Toluene (0.5)	20	76
19^c	Cs₂CO₃ (3.0)	Toluene (1)	20	60
20^d	Cs₂CO₃ (3.0)	Toluene (1)	30	65
21	Cs₂CO₃ (3.0)	Toluene (1)	12	63
22	Cs₂CO₃ (3.0)	Toluene (1)	30	83
23^e	Cs₂CO₃ (3.0)	Toluene (1)	20	n.d.
24	—	Toluene (1)	30	n.d.

[1]	Yanru Lin, Qian Zhou, Jinghao Qin, Dewei Song, Fangfang Song, Yuanyuan Gao, Huan Bao, Fei Li, Heng Jiang, Lantao Liu. Palladium-Catalyzed Intramolecular Heck/Amination of Unactivated Alkenes for the Synthesis of Spiroindolines [J]. Chinese Journal of Organic Chemistry, 2026, 46(8): 3139-3146.
[2]	Yumeng He, Fengyuan Zhou, Nan Jiang, Yuqi Zhang, Jijiang Wang, Haojie Ma. Iodine-Catalyzed Intramolecular Cyclization for the Synthesis of 2-Hydroxy-indolin-3-ones [J]. Chinese Journal of Organic Chemistry, 2026, 46(3): 961-967.
[3]	Xu Zhang, Peisen Zou, Xiaoqing Liu, Hongyan Bi, Dongliang Mo. Recent Progress in Gold-Catalyzed Intramolecular Cyclization of Alkynes and Its Applications [J]. Chinese Journal of Organic Chemistry, 2025, 45(10): 3755-3776.
[4]	Lizhi Zhang, Yongjian Liao, Ning Chen, Lei Huang, Min Zhou. Cyclization and Coupling Reactions Promoted by Potassium tert-Butoxide [J]. Chinese Journal of Organic Chemistry, 2022, 42(7): 1950-1959.
[5]	Jiazhuang Wang, Liguo Teng, Shaoqi Xiong, Tiebo Xiao, Yubo Jiang. Rh-Catalyzed gem-Difluoroallylation of N-Tosylhydrazones [J]. Chinese Journal of Organic Chemistry, 2022, 42(11): 3658-3667.
[6]	Yongxin Chen, Xin Guo, Yafeng Liu, Xueying Yang, Baohua Chen. Synthesis of 1,2,4-Triazolo[4,3-a]pyridines by I₂-Catalyzed Oxidative Coupling of 2-Aminopyridines with N-Tosylhydrazones [J]. Chinese Journal of Organic Chemistry, 2022, 42(11): 3863-3869.
[7]	Song Huayue, Liu Lin, Xie Xingang. Asymmetric Total Synthesis of the Possible Structure 1b of 15-Oxopuupehenoic Acid [J]. Chinese Journal of Organic Chemistry, 2020, 40(10): 3420-3425.
[8]	Chen Xuebing, Bai Hairui, Huang Chao. Concise Synthesis of Quinolinone Derivatives [J]. Chin. J. Org. Chem., 2017, 37(4): 881-888.
[9]	Jia Changqing, Su Wangcang, Xu Yanjun, Liu Jiping, Qin Zhaohai. Synthesis, Structure Characterization and Fungicidal Activity of 1,3-Disubstituted-1H-1,2,4-triazole-5-amines [J]. Chin. J. Org. Chem., 2016, 36(4): 830-837.
[10]	Bian Qinglong, Xu Sheng, Duan Weiliang. Base-Promoted Intramolecular Cyclization Reactions of Hexafluoro-isopropyl α,β-Alkenyl Sulfonates [J]. Chin. J. Org. Chem., 2015, 35(11): 2321-2325.
[11]	LUO Pei-Song, SHANG Ri-Yuan, ZHONG Beng, LI Jin-Heng. Progress in the Synthesis of Nitrogen-containing Heterocycles by In-tramolecular Cyclization of Alkynes [J]. Chin. J. Org. Chem., 2009, 29(12): 1924-1937.
[12]	MA Yuan*, YIN Wei, ZHAO Yu-Fen. Progress in Synthesis of 1-Indanones [J]. Chin. J. Org. Chem., 2008, 28(01): 37-43.
[13]	HUANG Li,ZHOU Ya-Ju,YE De-Yong*. Diastereoselectivity in Epoxidation of Allylic and Homoallylic Amidocycloalkenes of Varied Size [J]. Chin. J. Org. Chem., 2006, 26(03): 379-382.

光促进N-对甲苯磺酰腙的分子内C(sp³)—H/C=C插入环化反应研究

Light-Induced Intramolecular Cyclization through Insertion of N-Tosylhydrazone into C(sp³)—H and C=C Bonds

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光促进N-对甲苯磺酰腙的分子内C(sp3)—H/C=C插入环化反应研究