自由基介导的1,n-氮迁移反应研究进展

doi:10.6023/cjoc202512013

摘要/Abstract

自由基介导的1,n-氮迁移反应是一种新型的分子骨架修饰策略, 能够高效地实现含氮官能团在分子内的迁移, 因而在精准构建高价值含氮化合物的研究中受到广泛关注. 综述了基于迁移位点差异的三类氮迁移反应, 包括1,2-氮迁移、1,3-氮迁移以及远程氮迁移, 并分别探讨了它们在有机合成中的应用. 最后, 对该领域未来可能的发展方向进行了展望.

关键词: 自由基, 氮迁移, 重排, 不对称迁移

The radical-mediated 1,n-nitrogen migration reaction represents a novel strategy for skeleton rearrangement that enables the efficient intramolecular relocation of nitrogen-containing functional groups. As such, it has attracted considerable attention for the precise synthesis of high-value nitrogen-containing compounds. This review summarizes three types of nitrogen migration reactions classified by the migration site, including 1,2-nitrogen migration, 1,3-nitrogen migration, and remote nitrogen migration, along with their applications in organic synthesis. Furthermore, prospects for future development in this field are discussed.

Key words: radical, nitrogen migration, rearrangement, asymmetric migration

引用此文

陈嘉豪, 占贝贝, 张夏衡. 自由基介导的1,n-氮迁移反应研究进展[J]. 有机化学, 2026, 46(4): 1560-1571.

Jiahao Chen, Beibei Zhan, Xiaheng Zhang. Research Progress in Radical-Mediated 1,n-Nitrogen Migration Reactions[J]. Chinese Journal of Organic Chemistry, 2026, 46(4): 1560-1571.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

图/表 22

图式1. 自由基介导的1,n-氮迁移反应

Scheme 1. Radical-mediated 1,n-nitrogen migration

图式2. 自由基介导的1,2-氮迁移反应

Scheme 2. Radical-mediated 1,2-nitrogen migration

图式3. 铜催化的1,2-氮迁移反应合成α-氨基缩醛

Scheme 3. Copper-catalyzed 1,2-nitrogen migration for a-amino acetals synthesis

图式4. 铜催化三氟甲基化/1,2-氮迁移串联反应

Scheme 4. Copper-catalyzed trifluoromethylation/1,2-nitrogen migration cascade reaction

图式5. 铜催化的氧化环化/1,2-氮迁移串联反应

Scheme 5. Copper-catalyzed oxidative cyclization/1,2-nitrogen migration cascade reaction

图式6. 镍/硼协同催化1,2-氮迁移反应合成β-氨基酸酯

Scheme 6. Nickel/diboron cooperative catalysis for the synthesis of β-amino acid esters via 1,2-nitrogen migration

图式7. 镍催化BCBs开环/1,2-氮迁移串联反应

Scheme 7. Nickel-catalyzed BCBs ring-opening/1,2-nitrogen migration cascade reaction

图式8. 光催化仿生的1,2-氮迁移反应

Scheme 8. Visible-light-induced biomimetic 1,2-nitrogen migration

图式9. 镍催化的不对称交叉偶联/1,2-氮迁移串联反应

Scheme 9. Nickel-catalyzed asymmetric cross-coupling/1,2-nitrogen migration cascade reaction

图式10. 铜催化1,3-氮迁移反应合成吲哚类化合物

Scheme 10. Copper-catalyzed 1,3-nitrogen migration for indole synthesis

图式11. 钌、铁催化的对映选择性1,3-氮迁移反应合成手性α-氨基酸

Scheme 11. Ru or Fe-catalyzed enantioselective 1,3-nitrogen migration to access chiral α-amino acids

图式12. 非血红素铁酶催化的不对称1,3-氮迁移反应合成手性α-氨基酸

Scheme 12. Nonheme Fe 1,3-nitrogen migration for asymmetric chiral α-amino acids synthesis

图式13. 自由基介导的1,4-氮迁移反应

Scheme 13. Radical-mediated 1,4-nitrogen migration

图式14. 基于EDA策略的自由基1,4/5-氮迁移反应合成β(γ)-氨基酮

Scheme 14. Radical 1,4/5-nitrogen migration access to β(γ)-amino ketones via EDA strategy

图式15. 基于1,4-氮迁移的3-烯酸自由基脱羧1,2,3-三官能团化反应

Scheme 15. Radical decarboxylative 1,2,3-trifunctionalization of 3-enoic acids via 1,4-nitrogen migration

图式16. 基于1,4-氮迁移的三组分自由基反应合成β-氨基砜

Scheme 16. Radical three-component reaction for the synthesis of β-amino sulfones via 1,4-nitrogen migration

图式17. 可见光诱导的N-烷基苯甲酰胺N-α C(sp3)—H胺化反应

Scheme 17. Visible-light-induced N-α C(sp3)—H amination of N-alkyl benzamides

图式18. 钌催化的对映选择性1,6-氮迁移反应合成手性γ-氨甲基-γ-内酯

Scheme 18. Ru-catalyzed enantioselective 1,6-nitrogen migration to access chiral γ-aminomethyl-γ-lactones

图式19. 基于1,6-氮迁移的磺酰胺远程C(sp3)—H叠氮化反应

Scheme 19. Remote C(sp3)—H azidation of sulfamoyl azides via 1,6-nitrogen migration

图式20. 可见光诱导的碳胺化/1,4-氮迁移串联反应

Scheme 20. Visible-light-induced carboamination/1,4-nitrogen migration cascade reaction

图式21. 基于能量转移策略的1,4-氮迁移反应合成环氧化物

Scheme 21. EnT-enabled 1,4-nitrogen migration for epoxide synthesis

图式22. 可见光诱导的烷基胺化/1,5-氮迁移串联反应

Scheme 22. Visible-light-induced alkylamination/1,5-nitrogen migration cascade reaction

参考文献 77

[1]	Moyano, A.; El-Hamdouni, N.; Atlamsani, A. Chem.-Eur. J. 2010, 16, 5260.
[2]	Song, Z.-L.; Fan, C.-A.; Tu, Y.-Q. Chem. Rev. 2011, 111, 7523.
[3]	Zhang, X.-M.; Tu, Y.-Q.; Zhang, F.-M.; Chen, Z.-H.; Wang, S.-H. Chem. Soc. Rev. 2017, 46, 2272.
[4]	Wu, H.; Wang, Q.; Zhu, J. Eur. J. Org. Chem. 2019, 2019, 1964.
[5]	Du, Y.; Li, S.; Cheng, S.; Jia, H.; Wang, Z.; Han, L.; Zhu, N. Acta Chim. Sinica 2026, 84, 93 (in Chinese).
	(杜云哲, 李曙懿, 程思柳, 贾慧劼, 王政, 韩利民, 竺宁, 化学学报, 2026, 84, 93.)
[6]	Studer, A.; Bossart, M. Tetrahedron 2001, 57, 9649.
[7]	Chen, Z.-M.; Zhang, X.-M.; Tu, Y.-Q. Chem. Soc. Rev. 2015, 44, 5220.
[8]	Wu, X.; Zhu, C. Acc. Chem. Res. 2020, 53, 1620.
[9]	Wu, X.; Ma, Z.; Feng, T.; Zhu, C. Chem. Soc. Rev. 2021, 50, 11577.
[10]	Allen, A. R.; Noten, E. A.; Stephenson, C. R. J. Chem. Rev. 2022, 122, 2695.
[11]	Chen, Y.-S.; Cao, Z.; Wu, X.-X.; Zhu, C. Sci. Sinica Chim. 2023, 53, 289 (in Chinese).
	(陈亚苏, 曹柱, 吴新鑫, 朱晨, 中国科学: 化学, 2023, 53, 289.)
[12]	He, C.; Zhou, Y.; Duan, X.; Liu, L. Chin. J. Org. Chem. 2025, 45, 1478 (in Chinese).
	(贺重隆, 周有康, 段新华, 刘乐, 有机化学, 2025, 45, 1478.)
[13]	Chen, F.; Cao, Z.; Zhu, C. Chem. Commun. 2024, 60, 14912.
[14]	Matsuo, B.; Granados, A.; Majhi, J.; Sharique, M.; Levitre, G.; Molander, G. A. ACS Org. Inorg. Au 2022, 2, 435.
[15]	Jiang, X.-M.; Liu, X.-R.; Chen, A.; Zou, X.-Z.; Ge, J.-F.; Gao, D.-W. Eur. J. Org. Chem. 2022, e202101463.
[16]	Zhang, Y.; Zhou, G.; Liu, S.; Shen, X. Chem. Soc. Rev. 2025, 54, 1870.
[17]	Chen, F.; Cao, Z.; Zhu, C. Angew. Chem. Int. Ed. 2025, 64, e202424667.
[18]	Zhao, G.; Mukherjee, U.; Yao, W.; Ngai, M.-Y. Acc. Chem. Res. 2025, 58, 1815.
[19]	Chirpich, T. P.; Zappia, V.; Costilow, R. N.; Barker, H. A. J. Biol. Chem. 1970, 245, 1778.
[20]	Ding, L.; Fan, Y.; Lu, H. Chem. Soc. Rev. 2025, 54, 8145.
[21]	Han, O.; Frey, P. A. J. Am. Chem. Soc. 1990, 112, 8982.
[22]	Ballinger, M. D.; Reed, G. H.; Frey, P. A. Biochemistry 1992, 31, 949.
[23]	Ballinger, M. D.; Frey, P. A.; Reed, G. H. Biochemistry 1992, 31, 10782.
[24]	Wetmore, S. D.; Smith, D. M.; Radom, L. J. Am. Chem. Soc. 2001, 123, 8678.
[25]	Frey, P. A. Annu. Rev. Biochem. 2001, 70, 121.
[26]	Handa, S.; Rose, C. J. Tetrahedron Lett. 2004, 45, 8643.
[27]	Tian, J.-S.; Loh, T.-P. Angew. Chem. Int. Ed. 2010, 49, 8417.
[28]	Egami, H.; Kawamura, S.; Miyazaki, A.; Sodeoka, M. Angew. Chem. Int. Ed. 2013, 52, 7841.
[29]	Zhao, M.-N.; Zhang, Z.-J.; Ren, Z.-H.; Yang, D.-S.; Guan, Z.-H. Org. Lett. 2018, 20, 3088.
[30]	Hong, Y.; Liao, Z.-C.; Chen, J.-J.; Liu, J.; Liu, Y.-L.; Li, J.-H.; Sun, Q.; Chen, S.-L.; Wang, S.-W.; Tang, S. ACS Catal. 2024, 14, 5491.
[31]	Singha, T.; Bapat, N. A.; Mishra, S. K.; Hari, D. P. Org. Lett. 2024, 26, 6396.
[32]	Xia, P.-F.; Zhou, J.; Yuan, J.; Zeng, R.; Liu, Y.; Tang, K.-W.; Fan, J.-H. Org. Lett. 2024, 26, 6486.
[33]	Li, X.-Y.; Xiao, M.-Q.; Zhou, L.-J.; Zhang, J.-Q.; Zhao, M.-Y.; Wang, S.-W.; Tang, S. Chem. Commun. 2025, 61, 13473.
[34]	Fan, W.; Cui, Y.; Zhan, B.; Chen, Y.; Bao, L.; Liang, Y.; Zhang, X. Nat. Chem. 2025, 17, 941.
[35]	Ren, X.; Qiao, Y.; Zhou, B.; Liu, S.; Huang, Y. Nat. Synth. 2025, 4, 1232.
[36]	Liao, Z.; Li, Z.; Xiao, M.; Deng, Y.; Ma, Z.; Zhou, L.; Dai, G.; Li, X.; Wang, S.; Chen, S.; Li, J.; Tang, S. Nat. Commun. 2025, 16, 7218.
[37]	Wu, Z.; Ren, R.; Zhu, C. Angew. Chem., Int. Ed. 2016, 55, 10821.
[38]	Wu, Z.; Wang, D.; Liu, Y.; Huan, L.; Zhu, C. J. Am. Chem. Soc. 2017, 139, 1388.
[39]	Li, Y.; Wang, R.; Wang, T.; Cheng, X.-F.; Zhou, X.; Fei, F.; Wang, X.-S. Angew. Chem. Int. Ed. 2017, 56, 15436.
[40]	Blaskovich, M. A. T. J. Med. Chem. 2016, 59, 10807.
[41]	Mei, H.; Han, J.; White, S.; Graham, D. J.; Izawa, K.; Sato, T.; Fustero, S.; Meanwell, N. A.; Soloshonok, V. A. Chem.-Eur. J. 2020, 26, 11349.
[42]	Cheng, Z.; Kuru, E.; Sachdeva, A.; Vendrell, M. Nat. Rev. Chem. 2020, 4, 275.
[43]	Ye, C.-X.; Shen, X.; Chen, S.; Meggers, E. Nat. Chem. 2022, 14, 566.
[44]	Zhou, B.; Ye, C.-X.; Meggers, E. Eur. J. Org. Chem. 2023, 26, e202300296.
[45]	Yin, K.; Meggers, E. Synthesis 2024, 56, 2670.
[46]	Zhao, L.-P.; Liu, H.; Mai, B. K.; Zhang, Y.; Cheng, L.; Liu, P.; Yang, Y. Nat. Chem. Biol. 2025, 21, 1773.
[47]	Yang, Y.; Shi, S.-L.; Niu, D.; Liu, P.; Buchwald, S. L. Science 2015, 349, 62.
[48]	Lin, K.; Zhao, L.-P.; Wang, S.; Liu, H.; Zhang, Y.; Mai, B. K.; Liu, P.; Yang, Y. ChemRxiv 2025, doi: 10.26434/chemrxiv-2025-bvbtn.
[49]	Lin, K.; Zhao, L.-P.; Wang, S.; Liu, H.; Zhang, Y.; Mai, B. K.; Liu, P.; Yang, Y. Angew. Chem. Int. Ed. 2026, 65, e202524718.
[50]	Cheng, M.; Li, T.; Gan, Y.; Zhang, W.; Chen, X.; Zhao, Q. Angew. Chem. Int. Ed. 2026, 65, e202515741.
[51]	Yuan, T.; Zhang, M.; Cheng, L.; Zheng, X.; Jiang, S.; Huang, X.; Xiao, H. J. Am. Chem. Soc. 2025, 147, 44041.
[52]	Chen, Q.; Yu, J.; Li, S.; Wang, C.; Zheng, P.; Pan, H.-J. ChemCatChem 2025, 17, e00901.
[53]	Viswanathan, R.; Mutnick, D.; Johnston, J. N. J. Am. Chem. Soc. 2003, 125, 7266.
[54]	Wei, D.; Liu, T.; He, Y.; Wei, B.; Pan, J.; Zhang, J.; Jiao, N.; Han, B. Angew. Chem. Int. Ed. 2021, 60, 26308.
[55]	Lima, C. G. S.; Lima, T. Duarte, M.; Jurberg, I. D.; Paixão, M. W. ACS Catal. 2016, 6, 1389.
[56]	Postigo, A. Eur. J. Org. Chem. 2018, 6391.
[57]	Crisenza, G. E. M.; Mazzarella, D.; Melchiorre, P. J. Am. Chem. Soc. 2020, 142, 5461.
[58]	Liu, T.-M.; Xu, C.-Y.; Wang, Z.-S.; Gao, C.-H.; Li, Z.-H.; Han, B. ChemRxiv 2022, doi: 10.26434/chemrxiv-2022-vz567.
[59]	Zhang, Z.; Wang, J.; Yu, M.; Ye, S.; Wu, J. Org. Lett. 2023, 25, 304.
[60]	Li, L.-H.; Gu, X.-T.; Shi, M.; Wei, Y. Chem. Sci. 2022, 13, 12851.
[61]	Nie, X.; Ritter, C. W.; Hemming, M.; Ivlev, S. I.; Xie, X.; Chen, S.; Meggers, E. Angew. Chem. Int. Ed. 2023, 62, e202314398.
[62]	Li, J.; Zhong, S.; Zhou, P.; Li, X.; Xie, D.; Cai, Y.; Xia, Y. Org. Lett. 2024, 26, 3519.
[63]	Hu, S.-P.; Gao, C.-H.; Liu, T.-M.; Miao, B.-Y.; Wang, H.-C.; Yu, W.; Han, B. Angew. Chem. Int. Ed. 2024, 63, e202400168.
[64]	Teng, X.; Yu, T.; Shi, J.; Huang, H.; Wang, R.; Peng, W.; Sun, K.; Yang, S.; Wang, X. Adv. Synth. Catal. 2023, 365, 3211.
[65]	Wolff, M. E. Chem. Rev. 1963, 63, 55.
[66]	Liu, X.; Wang, L.; Zhang, M.; Tian, S.-K. Org. Lett. 2025, 27, 6743.
[67]	Wang, Q.-Z.; Zheng, Y.; Wu, W.-T.; Huang, H.-M. J. Am. Chem. Soc. 2025, 147, 16248.
[68]	Strieth-Kalthoff, F.; James, M. J.; Teders, M.; Pitzer, L.; Glorius, F. Chem. Soc. Rev. 2018, 47, 7190.
[69]	Zhou, Q.-Q.; Zou, Y.-Q.; Lu, L.-Q.; Xiao, W.-J. Angew. Chem. Int. Ed. 2019, 58, 1586.
[70]	Großkopf, J.; Kratz, T.; Rigotti, T.; Bach, T. Chem. Rev. 2022, 122, 1626.
[71]	Dutta, S.; Erchinger, J. E.; Strieth-Kalthoff, F.; Kleinmans, R.; Glorius, F. Chem. Soc. Rev. 2024, 53, 1068.
[72]	Liu, T.-M.; Zhu, L.-Y.; Qi, M.-H.; Li, S.-J.; Wang, X.-J.; Xu, J.-R.; Han, B. Chem. Sci. 2025, 16, 14811.
[73]	Chen, D.-N.; Qin, L.-L.; Luo, D.-J.; Lv, Y.; Yang, H.-Y.; Ye, D.-D.; Xia, P.-J. Org. Lett. 2025, 27, 5744.
[74]	Zhang, K.; Wang, M.; Jiang, Q.; Dong, B.; Duan, X.-H.; Liu, L. Sci. China Chem. 2026, 69, 858.
[75]	Strieth-Kalthoff, F.; Glorius, F. Chem 2020, 6, 1888.
[76]	Neveselý, T.; Wienhold, M.; Molloy, J. J.; Gilmour, R. Chem. Rev. 2022, 122, 2650.
[77]	Corpas, J.; Mauleón, P.; Arrayás, R. G.; Carretero, J. C. Adv. Synth. Catal. 2022, 364, 1348.