内烯烃烯丙基选择性C—H键胺化反应研究进展

doi:10.6023/cjoc202407007

摘要/Abstract

近年来, 内烯烃的烯丙基C—H键胺化反应发展迅速, 该类反应通过C—H键活化的方式高效地将氮源引入内烯烃的烯丙基位点构筑C—N键, 从而合成具有重要生物活性和药物前体的含氮化合物. 由于内烯烃活性较低, 并且在反应过程中存在化学选择性、区域选择性和立体选择性等多重挑战, 因此内烯烃的选择性烯丙基C—H键胺化反应一直是有机化学家的热门研究方向. 该综述主要介绍了近年来部分选择性内烯烃烯丙基C—H键胺化反应, 根据区分不同烯丙基C—H键的方法进行分类, 总结了该领域的研究进展及该反应在合成生物活性分子中的应用潜力.

关键词: 内烯烃, 烯丙基, 胺化反应

In recent years, the allylic C—H amination of internal olefins has undergone rapid development. This reaction introduces nitrogen sources into the allylic positions of internal olefins via C—H activation efficiently to form new C—N bonds, thereby synthesizing nitrogen-containing compounds with significant biological activity and pharmaceutical potential. Given the relatively low reactivity of internal olefins and the challenges of chemoselectivity, regioselectivity and stereoselectivity during the reaction, the allylic C—H amination of internal olefins has been a great challenge for organic chemists. This review primarily covers the selective allylic C—H amination of internal olefins in recent years, categorizing the methods based on the mechanism of distinguishing different allylic C—H bonds to achieve selective amination, and summarizes the research progress in this field and its potential applications in synthesizing biologically active molecules.

Key words: internal olefin, allylic, amination

引用此文

厍远, 张书宇, 王乐. 内烯烃烯丙基选择性C—H键胺化反应研究进展[J]. 有机化学, 2025, 45(2): 531-545.

Yuan She, Shuyu Zhang, Le Wang. Advances in Selective Allylic C—H Amination of Internal Olefins[J]. Chinese Journal of Organic Chemistry, 2025, 45(2): 531-545.

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

分享此文

图/表 34

图式1. 常见的烯丙基C—H键胺化反应

Scheme 1. Common allylic C—H amination reactions

图式2. Cp*IrIII催化的分子间烯丙基C—H键胺化反应

Scheme 2. Cp*IrIII-catalyzed intermolecular allylic C—H amination

图式3. Cp*IrIII催化分子间烯丙基C—H键胺化反应底物拓展

Scheme 3. Substrate scope expansion for Cp*IrIII-catalyzed intermolecular allylic C—H amination

图式4. Cp*IrIII催化的分子间烯丙基C—H键胺化反应机理

Scheme 4. Mechanistic study of Cp*IrIII-catalyzed intermolecular allylic C—H amination

图式5. 平面构型的手性茚基铑催化剂选择性催化烯丙基C—H键胺化反应

Scheme 5. A planar chiral rhodium indenyl catalyst for selective allylic C—H amination

图式6. 手性茚基铑催化烯丙基C—H键胺化反应底物拓展

Scheme 6. Substrate scope expansion for the chiral rhodium indenyl catalyst for selective allylic C—H amination

图式7. 手性茚基铑催化的烯丙基C—H键胺化反应机理

Scheme 7. Mechanism of chiral indenyl-rhodium-catalyzed allylic C—H amination reaction

图式8. 通过1JCH的差值(Δ1JCH)对C—H键的选择性胺化进行预测

Scheme 8. Predicting selective C—H amination using the difference in 1JCH (Δ1JCH)

图式9. 1,1-二取代烯烃及内烯烃类化合物的底物拓展

Scheme 9. Substrate scope expansion of 1,1-disubstituted and internal olefin compounds

图式10. 乙烯硅烷和乙烯硼酸酯的烯丙基C—H键胺化反应

Scheme 10. Allylic C—H amination reaction of vinylsilanes and vinylboronates

图式11. 乙烯硅烷和乙烯硼酸酯的烯丙基C—H胺化反应底物拓展

Scheme 11. Substrate scope expansion for the allylic C—H amination reaction targeting vinylsilanes and vinylboronates

图式12. 乙烯硅烷和乙烯硼酸酯的烯丙基C—H胺化反应催化循环机理

Scheme 12. Catalytic cycle mechanism for the allylic C—H amination reaction of vinylsilanes and vinylboronates

图式13. 利用β-硅效应促进的烯丙基硅烷分子间C—H键胺化反应

Scheme 13. Intermolecular C—H amination of allylsilanes promoted by the β-silicon effect

图式14. β-硅效应促进的烯丙基硅烷分子间C—H键胺化反应底物拓展

Scheme 14. Substrate scope expansion for intermolecular C—H amination of allylsilanes promoted by the β-silicon effect

图式15. β-硅效应促进烯丙基硅烷分子间C—H键胺化的反应机理

Scheme 15. Mechanism of intermolecular C—H amination of allylsilanes promoted by the β-silicon effect

图式16. B(MIDA)导向的烯丙基/炔丙基选择性C—H键胺化反应

Scheme 16. B(MIDA) directed selective allylic/propargylic C—H amination reaction

图式17. B(MIDA)导向的烯丙基选择性C—H键胺化反应底物拓展

Scheme 17. Substrate scope expansion for B(MIDA) directed allylic selective C—H amination reaction

图式18. B(MIDA)导向的烯丙基选择性C—H键胺化反应机理研究

Scheme 18. Mechanistic study of B(MIDA) directed allylic selective C—H amination reaction

图式19. 8-氨基喹啉导向的未活化内烯烃的烯丙基C—H键胺化反应

Scheme 19. 8-Aminoquinoline directed allylic C—H amination of inactivated internal olefins

图式20. 8-氨基喹啉导向的未活化内烯烃的烯丙基C—H键胺化反应底物拓展

Scheme 20. Substrate scope expansion for 8-aminoquinoline directed allylic C—H amination of inactivated internal olefins

图式21. 8-氨基喹啉导向的未活化内烯烃的烯丙基C—H键胺化反应可能的反应机理

Scheme 21. Plausible mechanism for 8-aminoquinoline directed allylic C—H amination of inactivated internal olefins

图式22. 可持续锰催化剂[MnIII(ClPc)]作用于后期选择性烯丙基C—H键胺化反应

Scheme 22. Sustainable manganese catalyst [MnIII(ClPc)] for late-stage selective allylic C—H amination

图式23. 可持续锰催化剂[MnIII(ClPc)]选择性C—H键胺化反应底物拓展

Scheme 23. Substrate scope expansion for sustainable manganese catalyst [MnIII(ClPc)] for late-stage selective C—H amination

图式24. 可持续锰催化剂[MnIII(ClPc)]选择性烯丙基C—H键胺化反应机理

Scheme 24. Mechanism of allylic selective C—H amination reaction with sustainable manganese catalyst [MnIII(ClPc)]

图式25. 空间差异和立体电子差异对可持续锰催化剂[MnIII(ClPc)]胺化位点的影响

Scheme 25. Influence of steric and stereoelectronic differences on amination sites with sustainable manganese catalyst

图式26. 铑(II)催化的烯丙基1,3-二胺化反应

Scheme 26. Rhodium(II)-catalyzed allylic 1,3-diamination reaction

图式27. 铑(II)催化烯丙基1,3-二胺化反应的底物拓展

Scheme 27. Substrate scope expansion for rhodium(II)-catalyzed allylic 1,3-diamination reaction

图式28. 铑(II)催化的烯丙基1,3-二胺化机理实验

Scheme 28. Experimental investigation of rhodium(II)-catalyzed allylic 1,3-diamination mechanism

图式29. 铑(II)催化的内烯烯丙基1,3-二胺化反应机理

Scheme 29. Mechanism of rhodium(II)-catalyzed internal olefins allylic 1,3-diamination reaction

图式30. 基于蓝光诱导的Pd(0/I/II)催化烯丙基C—H键胺化反应

Scheme 30. Blue-light-induced Pd(0/I/II)-catalyzed allylic C—H amination

图式31. 基于蓝光诱导的Pd(0/I/II)催化烯丙基C—H键胺化反应过程

Scheme 31. Blue-light-induced Pd(0/I/II)-catalyzed allylic C—H amination process

图式32. Pd(0/I/II)催化烯丙基C—H键胺化潜在的副反应以及自由基前体优化

Scheme 32. Potential side reactions and radical precursors optimization in Pd(0/I/II)-catalyzed allylic C—H amination

图式33. 基于蓝光诱导的Pd(0/I/II)催化烯丙基C—H键胺化反应底物拓展

Scheme 33. Substrate scope expansion for blue-light-induced Pd(0/I/II)-catalyzed allylic C—H amination

图式34. 基于蓝光诱导的Pd(0/I/II)催化立体选择性C—H键胺化反应

Scheme 34. Blue-light-induced Pd(0/I/II)-catalyzed stereoselective C—H amination

参考文献 21

[1]	Vitaku, E.; Smith, D. T.; Njardarson, J. T. J. Med. Chem. 2014, 57, 10257. doi: 10.1021/jm501100b pmid: 25255204
[2]	Brown, D. G.; Boström, J. J. Med. Chem. 2016, 59, 4443. doi: 10.1021/acs.jmedchem.5b01409 pmid: 26571338
[3]	Park, Y.; Kim, Y.; Chang, S. Chem. Rev. 2017, 117, 9247.
[4]	Wender, P. A.; Verma, V. A.; Paxton, T. J.; Pillow, T. H. Acc. Chem. Res. 2008, 41, 40.
[5]	Trost, B. M.; Hansmann, M. M.; Thaisrivongs, D. A. Angew. Chem., Int. Ed. 2012, 51, 4950.
[6]	Davies, H. M. L.; Mortona, D. Chem. Soc. Rev. 2011, 40, 1857. doi: 10.1039/c0cs00217h pmid: 21359404
[7]	Cernak, T.; Dykstra, K. D.; Tyagarajan, S.; Vachalb, P.; Krskab, S. W. Chem. Soc. Rev. 2016, 45, 546. doi: 10.1039/c5cs00628g pmid: 26507237
[8]	Pàmies. O.; Margalef. J. S.; Judge. E.; Guiry. P. J.; Moberg. C.; Pericas. M. A. Chem. Rev. 2021, 121, 4373. doi: 10.1021/acs.chemrev.0c00736 pmid: 33739109
[9]	Burman, J. S.; Harris, R. J.; Farr, C. M. B.; Bacsa, J.; Blakey, S. B. ACS Catal. 2019, 9, 5474. doi: 10.1021/acscatal.9b01338
[10]	Bayeh, L.; Tambar, U. K. ACS Catal. 2017, 7, 8533.
[11]	Bayeh, L.; Le, P.; Tambar, U. K. Nature 2017, 547, 196.
[12]	Knecht, T.; Mondal, S.; Ye, J.-H.; Das, M.; Glorius, F. Angew. Chem., Int. Ed. 2019, 58, 7117.
[13]	Farr, C. M. B.; Kazerouni, A. M.; Park, B.; Poff, C. D.; Won, J.; Sharp, K. R.; Baik, M. H.; Blakey, S. B. J. Am. Chem. Soc. 2020, 142, 13996.
[14]	Lei, H.; Rovis, T. Nat. Chem. 2020, 12, 725.
[15]	Maloney, T. P.; Berman, J. L.; Michael, F. E. Angew. Chem., Int. Ed. 2022, 61, e202210109.
[16]	Lin, S.; Liu, Y.; Gao, K.-Y.; Chen, Z.-H.; Qian, J.; Liu, X.-B.; Li, Q.; Wang, H. ACS Catal. 2024, 14, 8865.
[17]	Liu, Y.; Chen, Z.-H.; Li, Y.; Qian, J.; Li, Q.-J.; Wang, H.-G. J. Am. Chem. Soc. 2022, 144, 14380.
[18]	Wang, L.; Wang, C.-L.; Li, Z.-H.; Lian, P.-F.; Kang, J.-C.; Zhou J.; Hao, Y.; Liu, R.-X.; Bai, H.-Y.; Zhang, S.-Y. Nat. Commun. 2024, 15, 1483. doi: 10.1038/s41467-024-45875-y pmid: 38374064
[19]	Ide, T.; Feng, K.; Dixon, C. F.; Teng, D.; Clark, J. R.; Han, W.; Wendell, C. I.; Koch, V.; White, M. C. J. Am. Chem. Soc. 2021, 143, 14969.
[20]	Yang, B.; Liu, X.; Yu, A.; Yang, Q.; Wang, Y. ACS Catal. 2022, 12, 13411.
[21]	Cheung, K. P. S.; Fang, J.; Mukherjee, K.; Mihranyan, A.; Gevorgyan, V. Science 2022, 378, 1207.