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2025 , Vol. 45 >Issue 4: 1047 - 1096

DOI: https://doi.org/10.6023/cjoc202408019

综述与进展

N-邻位C(sp3)—H键官能团化合成含氮杂环化合物研究进展

  • 范玉兰 ,
  • 邹小颖 ,
  • 朱小青 ,
  • 郑绿茵 ,
  • 郭维
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  • 赣南师范大学化学化工学院 合成药物化学江西重点实验室 江西赣州 341000

收稿日期: 2024-08-15

  修回日期: 2024-09-20

  网络出版日期: 2024-11-08

基金资助

国家自然科学基金(22167002); 国家自然科学基金(22467001)

收起

Progress in N-α-C(sp3)—H Bond Functionalization for the Synthesis of N-Heterocycles

  • Yulan Fan ,
  • Xiaoying Zou ,
  • Xiaoqing Zhu ,
  • Lüyin Zheng ,
  • Wei Guo
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  • Jiangxi Provincial Key Laboratory of Synthetic Pharmaceutical Chemistry, College of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou, Jiangxi 341000
* E-mail: ;

Received date: 2024-08-15

  Revised date: 2024-09-20

  Online published: 2024-11-08

Supported by

National Natural Science Foundation of China(22167002); National Natural Science Foundation of China(22467001)

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摘要

C(sp3)—H键官能团化是当前有机合成领域的研究热点. N-邻位C(sp3)—H键中的氮原子上孤对电子与邻位碳自由基的单占分子轨道(SOMO)中的电子发生离域后, 降低了C(sp3)—H键的解离能, 有利于引入各种亲核试剂或亲偶极试剂, 通过分子间或分子内亲核环化或偶极环化反应得到结构多样的含氮杂环化合物. 按照N-邻位C(sp3)—H键在不同条件下形成亚胺离子、α-氨基烷基自由基和甲亚胺叶立德等三种中间体进行分类, 综述了近年来N-邻位C(sp3)—H键官能团化合成含氮杂环化合物的研究进展, 阐述了可能经历的化学反应历程, 对其应用前景进行了展望.

关键词： N-邻位C(sp3)—H键; 亚胺离子; α-氨基烷基自由基; 甲亚胺叶立德; 含氮杂环化合物

本文引用格式

范玉兰 , 邹小颖 , 朱小青 , 郑绿茵 , 郭维 . N-邻位C(sp3)—H键官能团化合成含氮杂环化合物研究进展[J]. 有机化学, 2025 , 45(4) : 1047 -1096 . DOI: 10.6023/cjoc202408019

Abstract

C(sp3)—H bond functionalization is currently a research hotspot in the field of organic synthesis. The delocalization effect between lone-pair electrons on the nitrogen atom in the N-α-C(sp3)—H bond with the electrons in single occupied molecular orbital (SOMO) of the neighboring carbon radical can reduce the dissociation energy of the C(sp3)—H bond, which facilitates the introduction of various nucleophilic or dipolar reagents into N-α-C(sp3) to provide a variety of nitrogen-contain- ing heterocyclic compounds with diverse structures through intermolecular or intramolecular nucleophilic annulation or dipole cyclization reactions. The research progress in N-α-C(sp3)—H bond functionalization for the synthesis of nitrogen-containing heterocyclic compounds under different conditions through the formation of iminium ions, α-aminoalkyl radicals, and azomethimine ylide intermediates is summarized. The possible reaction processes and their potential applications are discussed.

Key words： N-α-C(sp3)—H bond; iminium ions; α-aminoalkyl radicals; azomethimine ylides; N-heterocycles

参考文献

[1]
(a) Chugh, A.; Kumar, A.; Verma, A.; Kumar, S.; Kumar, P. Med. Chem. Res. 2020, 29, 1723.
[1]
(b) Kumari, S.; Maddeboina, K.; Bachu, R. D.; Boddu, S. H. S.; Trippier, P. C.; Tiwari, A. K. Drug Discovery Today 2022, 27, 103322.
[1]
(c) Mermer, A.; Keles, T.; Sirin, Y. Bioorg. Chem. 2021, 114, 105076.
[2]
(a) Vitaku, E.; Smith, D. T.; Njardarson, J. T. J. Med. Chem. 2014, 57, 10257.
[2]
(b) Heravi, M. M.; Zadsirjan, V. RSC Adv. 2020, 10, 44247.
[3]
(a) Freund, R.; Zaremba, O.; Arnauts, G.; Ameloot, R.; Skorupskii, G.; Dincǎ, M.; Bavykina, A.; Gascon, J.; Ejsmont, A.; Goscianska, J.; Kalmutzki, M.; L?chelt, U.; Ploetz, E.; Diercks, C. S.; Wuttke, S. Angew. Chem. Int. Ed. 2021, 60, 23975.
[3]
(b) Zhang, Q.; Jiang, S.; Lv, T.; Peng, Y.; Pang, H. Adv. Mater. 2023, 35, 2305532.
[3]
(c) Zheng, L.; Deng, L.; Zhong, Y.; Wang, Y.; Guo, W.; Fan, X. Parasitol. Res. 2021, 120, 3355.
[4]
(a) Zheng, L.; Tao, K.; Guo, W. Adv. Synth. Catal. 2021, 363, 62.
[4]
(b) Guo, W.; Zhao, M.; Tan, W.; Zheng, L.; Tao, K.; Fan, X. Org. Chem. Front. 2019, 6, 2120.
[5]
(a) Godula, K.; Sames, D. Science 2006, 312, 67.
[5]
(b) Bergman, R. G. Nature 2007, 446, 391.
[5]
(c) Li, J.-Z.; Mei, L.; Yu, X.-C.; Wang, L.-T.; Cai, X.-E.; Li, T.; Wei, W.-T. Org. Chem. Front. 2022, 9, 5726.
[6]
Zhu, Z.; Xiao, L.; Xie, Z.; Le, Z. Chin. J. Org. Chem. 2019, 39, 2345 (in Chinese).
[6]
(祝志强, 肖利金, 谢宗波, 乐长高, 有机化学, 2019, 39, 2345.)
[7]
Luo, Y. R. Handbook of Bond Dissociation Energy in Organic Compound, CRC Press, Boca Raton, 2002.
[8]
(a) Hou, W.; Jia, X. Chin. J. Org. Chem. 2018, 38, 999 (in Chinese).
[8]
(侯文涛, 贾晓东, 有机化学, 2018, 38, 999.)
[8]
(b) Liu, S.; Zhao, Z.; Wang, Y. Chem.-Eur. J. 2019, 25, 2423.
[8]
(c) Tashrifi, Z.; Khanaposhtani, M. M.; Larijani, B.; Mahdavi, M. Asian J. Org. Chem. 2021, 10, 2421.
[9]
(a) Hu, J.; Wang, J.; Nguyen, T. H.; Zheng, N. Beilstein J. Org. Chem. 2013, 9, 1977.
[9]
(b) Hoffmann, N. J. Phys. Org. Chem. 2015, 28, 121.
[9]
(c) Bao, X.; Jiang, W.; Liang, J.; Huo, C. Org. Chem. Front. 2020, 7, 2107.
[9]
(d) Kratena, N.; Marinic, B.; Donohoe, T. J. Chem. Sci. 2022, 13, 14213.
[10]
(a) Wolan, A.; Kowalska-Six, J. A.; Rajerison, H.; Césario, M.; Cordier, M.; Six, Y. Tetrahedron 2018, 74, 5248.
[10]
(b) Cui, H.-L. Org. Biomol. Chem. 2022, 20, 2779.
[10]
(c) Jacobs, J.; Van Hende, E.; Claessens, S.; De Kimpe, N. Curr. Org. Chem. 2011, 15, 1340.
[11]
Liu, P.; Li, Y.; Wang, H.; Wang, Z.; Hu, X. Tetrahedron Lett. 2012, 53, 6654.
[12]
Huo, C.; Yuan, Y.; Chen, F.; Tang, J.; Wang, Y. Org. Lett. 2015, 17, 4208.
[13]
Sengoden, M.; Bhowmick, A.; Punniyamurthy, T. Org. Lett. 2017, 19, 158.
[14]
Li, H.; Huang, S.; Wang, Y.; Huo, C. Org. Lett. 2018, 20, 92.
[15]
Basavaiah, D.; Lingaiah, B.; Reddy, G. C.; Sahu, B. C. Eur. J. Org. Chem. 2016, 2016, 2398.
[16]
Wang, W.; Sun, J.; Hu, H.; Liu, Y. Org. Biomol. Chem. 2018, 16, 1651.
[17]
Regalla, V. R.; Addada, R. R.; Chatterjee, A. Tetrahedron Lett. 2018, 59, 4161.
[18]
Xie, Z.; Li, F.; Niu, L.; Li, H.; Zheng, J.; Han, R.; Ju, Z.; Li, S.; Li, D. Org. Biomol. Chem. 2020, 18, 6889.
[19]
Huo, C.; Yuan, Y.; Wu, M.; Jia, X.; Wang, X.; Chen, F.; Tang, J. Angew. Chem. Int. Ed. 2014, 53, 13544.
[20]
Huang, S.; Bao, X.; Fu, Y.; Zhang, Y.; Quan, Z.; Huo, C. Asian J. Org. Chem. 2020, 9, 925.
[21]
Deb, M. L.; Borpatra, P. J.; Baruah, P. K. Green Chem. 2019, 21, 69.
[22]
Karjee, P.; Sarkar, T.; Kar, S.; Punniyamurthy, T. J. Org. Chem. 2020, 85, 8261.
[23]
Mao, W.; Zhao, H.; Zhang, M. Chem. Commun. 2022, 58, 4380.
[24]
Hu, B.; Dong, W.; Feng, Z.; Gao, X.; Gao, H.; Xie, X.; Zhang, Z. Asian J. Org. Chem. 2016, 5, 1467-1470.
[25]
Zhang, Y.; Li, S.; Zhu, Y.; Yang, X.; Zhou, H.; Li, Y. J. Org. Chem. 2020, 85, 6261.
[26]
Wang, J.; Li, L.; Guo, Y.; Li, S.; Wang, S.; Li, Y.; Zhang, Y. Org. Biomol. Chem. 2020, 18, 8179.
[27]
Luo, K.; Zhao, Y.; Tang, Z.; Li, W.; Lin, J.; Jin, Y. Org. Lett. 2022, 24, 6335.
[28]
Borpatra, P. J.; Deb, M. L.; Baruah, P. K. Tetrahedron Lett. 2017, 58, 4006.
[29]
Wang, L.; Ma, T.; Qiao, M.; Wu, Q.; Shi, D.; Xiao, W. Synthesis 2019, 51, 522.
[30]
Vijay, M.; Kumar, S. V.; Satheesh, V.; Ananthappan, P.; Srivastava, H. K.; Ellairaja, S.; Vasantha, V. S.; Punniyamurthy, T. Org. Lett. 2019, 21, 7649.
[31]
Yu, D.; Liu, Y.; Che, C.-M. Org. Chem. Front. 2022, 9, 2779.
[32]
Sakai, N.; Matsumoto, S.; Ogiwara, Y. Tetrahedron Lett. 2016, 57, 5449.
[33]
Ma, X.; Zhu, Y.; Lü, S.; Zhang, L.; Luo, L.; Jia, X. Tetrahedron Lett. 2016, 57, 1528.
[34]
Jia, X.; Li, P.; Shao, Y.; Yuan, Y.; Hou, W; Liu, X.; Zhang, X.; Ji, H. Chem.-Asian J. 2017, 12, 1719.
[35]
Zhang, X.; Li, P.; Yuan, Y.; Jia, X. Chin. J. Org. Chem. 2018, 38, 2435 (in Chinese).
[35]
(张学文, 李鹏飞, 袁宇, 贾晓东, 有机化学, 2018, 38, 2435.)
[36]
Wei, W.-T.; Teng, F.; Li, Y.; Song, R.-J.; Li, J.-H. Org. Lett. 2019, 21, 6285.
[37]
Hwang, J. Y.; Ji, A. Y.; Lee, S. H.; Kang, E. J. Org. Lett. 2020, 22, 16.
[38]
Yuan, Y.; Zhang, S.; Sun, Z.; Su, Y.; Ma, Q.; Yuan, Y.; Jia, X. Org. Lett. 2020, 22, 6294.
[39]
Jia, X.; Wang, Y.; Peng, F.; Huo, C.; Yu, L.; Liu, J.; Wang, X. Adv. Synth. Catal. 2014, 356, 1210.
[40]
Lü, S.; Zhu, Y.; Ma, X.; Jia, X. Adv. Synth. Catal. 2016, 358, 1004.
[41]
Jia, X.; Zhu, Y.; Yuan, Y.; Zhang, X.; Lü, S.; Zhang, L.; Luo, L. ACS Catal. 2016, 6, 6033.
[42]
Luo, L.; Zhao, X.; Zhang, L.; Yuan, Y.; Lü, S.; Jia, X. Tetrahedron Lett. 2016, 57, 5830.
[43]
Jia, X.; Lü, S.; Yuan, Y.; Zhang, X.; Zhang, L.; Luo, L. Org. Biomol. Chem. 2017, 15, 2931.
[44]
Ji, H.; Zhu, Y.; Shao, Y.; Liu, J.; Yuan, Y.; Jia, X. J. Org. Chem. 2017, 82, 9859.
[45]
Luo, Z.; Han, X.; Liu, C.; Liu, Q.; Li, R.; Liu, P.; Xu, X. Synthesis 2020, 52, 1067.
[46]
Nakajima, K.; Kitagawa, M.; Ashida, Y.; Miyake, Y.; Nishibayashi, Y. Chem. Commun. 2014, 50, 8900.
[47]
Hou, H.; Zhu, S.; Pan, F.; Rueping, M. Org. Lett. 2014, 16, 2872.
[48]
Liang, Z.; Xu, S.; Tian, W.; Zhang, R. Beilstein J. Org. Chem. 2015, 11, 425.
[49]
Hsu, C.-W.; Sundén, H. Org. Lett. 2018, 20, 2051.
[50]
Yang, X.-L.; Guo, J.-D.; Lei, T.; Chen, B.; Tung, C.-H.; Wu, L.-Z. Org. Lett. 2018, 20, 2916.
[51]
Yuan, X.; Wu, X.; Dong, S.; Wu, G.; Ye, J. Org. Biomol. Chem. 2016, 14, 7447.
[52]
Zhao, Y.; Chen, J.-R.; Xiao, W.-J. Org. Lett. 2016, 18, 6304.
[53]
Liu, J.; Xie, J.; Zhu, C. Org. Chem. Front. 2017, 4, 2433.
[54]
Natarajan, P.; Chuskit, D.; Priya Green Chem. 2019, 21, 4406.
[55]
Gao, Z.-H.; Xia, Z.-H.; Dai, L.; Ye, S. Adv. Synth. Catal. 2020, 362, 1819.
[56]
Zhang, Y.; Jiang, W.; Bao, X.; Qiu, Y.; Yuan, Y.; Yang, C.; Huo, C. Chin. J. Chem. 2021, 39, 3238.
[57]
Wang, H.-T.; Lu, C.-D. Tetrahedron Lett. 2013, 54, 3015.
[58]
Chen, X.-H.; Pan, Y.-Y.; Wang, W.-X.; Cui, H.-L. Synlett 2022, 33, 1645.
[59]
Sugimoto, K.; Yamamoto, N.; Tominaga, D.; Matsuya, Y. Org. Lett. 2015, 17, 1320.
[60]
Motornov, V. A.; Tabolin, A. A.; Nelyubina, Y. V.; Nenajdenko, V, G.; Ioffe, S. L. Org. Biomol. Chem. 2019, 17, 1442.
[61]
Motornov, V. A.; Tabolin, A. A.; Ioffe, S. L. New J. Chem. 2022, 46, 4134.
[62]
Miao, C.-B.; Qiang, X.-Q.; Xu, X.; Song, X.-Q.; Zhou, S.-Q.; Lyu, X.; Yang, H.-T. Org. Lett. 2022, 24, 3828.
[63]
Huang, H.-M.; Li, Y.-J.; Ye, Q.; Yu, W.-B.; Han, L.; Jia, J.-H.; Gao, J.-R. J. Org. Chem. 2014, 79, 1084.
[64]
Huang, H.-M.; Huang, F.; Li, Y.-J.; Jia, J.-H.; Ye, Q.; Han, L.; Gao, J.-R. RSC Adv. 2014, 4, 27250.
[65]
Yang, Z.; Lu, N.; Wei, Z.; Cao, J.; Liang, D.; Duan, H.; Lin, Y. J. Org. Chem. 2016, 81, 11950.
[66]
Huang, H.-M.; Gao, J.-R.; Ye, Q.; Yu, W.-B.; Sheng, W.-J.; Li, Y.-J. RSC Adv. 2014, 4, 15526.
[67]
Zhu, Z.; Seidel, D. Org. Lett. 2017, 19, 2841.
[68]
Zheng, K.; Zhuang, S.; You, M.; Shu, W.; Wu, A.; Wu, Y. ChemistrySelect 2017, 2, 10762.
[69]
Zheng, K.-L.; You, M.-Q.; Shu, W.-M.; Wu, Y.-D.; Wu, A.-X. Org. Lett. 2017, 19, 2262.
[70]
Vyasamudri, S.; Yang, D.-Y. J. Org. Chem. 2019, 84, 3662.
[71]
Wang, K.-K.; Li, Y.-L.; Wang, Z.-Y.; Ma, X.; Mei, Y.-L.; Zhang, S.-S.; Chen, R. J. Heterocycl. Chem. 2020, 57, 1456.
[72]
Li, F.; Chen, J.; Hou, Y.; Li, Y.; Wu, X.-Y.; Tong, X. Org. Lett. 2015, 17, 5376.
[73]
Jadala, C.; Reddy, V. G.; Krishna, N. H.; Shankaraiah, N.; Kamal, A. Org. Biomol. Chem. 2020, 18, 8694.
[74]
Hou, X.; Zhou, S.; Li, Y.; Guo, M.; Zhao, W.; Tang, X.; Wang, G. Org. Lett. 2020, 22, 9313.
[75]
Aksenov, A. V.; Arutiunov, N. A.; Kirilov, N. K.; Aksenov, D. A.; Grishin, I. Y.; Aksenov, N. A.; Wang, H.; Du, L.; Betancourt, T.; Pelly, S. C.; Kornienko, A.; Rubin, M. Org. Biomol. Chem. 2021, 19, 7234.
[76]
Yang, L.-M.; Zhang, Y.-Y.; Deng, J.-T.; Ma, A.-J.; Zhang, X.-Z.; Zhang, S.-Y.; Peng, J.-B. Asian J. Org. Chem. 2021, 10, 1679.
[77]
Izmest'ev, A. N.; Motornov, V. A.; Vinogradov, D. B.; Ioffe, S. L.; Kravchenko, A. N.; Gazieva, G. A. Org. Chem. Front. 2022, 9, 4998.
[78]
Zhang, X.; Wang, X.; Jiao, C.; Zhao, J.; Liu, X.; Zhang, G. Org. Chem. Front. 2022, 9, 5516.
[79]
Wang, Q.; Yuan, T.; Liu, Q.; Xu, Y.; Xie, G.; Lv, X.; Ding, S.; Wang, X.; Li, C. Chem. Commun. 2019, 55, 8398.
[80]
Kumar, R.; Banerjee, P. J. Org. Chem. 2021, 86, 16104.
[81]
Koohgard, M.; Hosseini-Sarvari, M. J. Photochem. Photobiol. A 2021, 404, 112877.
[82]
Zheng, L.; Zou, X.; Yang, X.; Deng, L.; Guo, W. Adv. Synth. Catal. 2023, 365, 3629.
[83]
Mailloux, M. J.; Fleming, G. S.; Kumta, S. S.; Beeler, A. B. Org. Lett. 2021, 23, 525.
[84]
Qu, Z.; Zhang, F.; Deng, G.-J.; Huang, H. Org. Lett. 2019, 21, 8239.
[85]
Wang, D.; Xiao, F.; Zhang, F.; Huang, H.; Deng, G.-J. Chin. J. Chem. 2021, 39, 87.
[86]
Kadu, V. D.; Khadul, S. P.; Kothe, G. J.; Mali, G. A. Asian J. Org. Chem. 2022, 11, e202200162.
[87]
Camats, M.; Favier, I.; Mallet-Ladeira, S.; Pla, D.; Gómez, M. Org. Biomol. Chem. 2022, 20, 219.
[88]
Kadu, V. D.; Sankala, N. C.; Hublikar, M. G.; Bansode, S. I.; Bhosale, R. B. Synthesis 2024, 56, 2277.
[89]
Wang, K.; Sun, Y.; Li, B.; Zhang, X.; Fan, X. Org. Lett. 2024, 26, 3091.
[90]
Shen, J.; Cai, D.; Kuai, C.; Liu, Y.; Wei, M.; Cheng, G.; Cui, X. J. Org. Chem. 2015, 80, 6584.
[91]
Qin, Q.; Yu, S. Org. Lett. 2015, 17, 1894.
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