吲哚氮杂环作为自由基受体在串联环化反应中的研究进展

doi:10.6023/cjoc202107012

摘要/Abstract

含吲哚骨架衍生物因其具有多样的生物活性, 广泛应用于生物活性分子的合成与修饰, 特别是在药物化学、农药化学领域中. 近年来, 高效的吲哚环合成与后官能化反应已成为热门的研究主题, 例如吲哚的不对称去芳构化反应构建螺环衍生物. 不饱和烃的自由基串联反应一直是有机化学的一个重要研究分支, 含吲哚母体的不饱和烃串联环化反应已经成为吲哚骨架修饰的一种重要途径. 因此, 综述了吲哚骨架中氮杂环作为自由基受体在不饱和烃串联环化反应中的研究进展, 并对反应设计、机理研究、研究展望等给予评述.

关键词: 吲哚, 自由基, 串联环化反应, 不饱键, 双官能化

Indole skeleton has been widely utilized in the synthesis and late-stage modification of biologically active compounds, especially in the fields of medicines and pesticides. In recent years, constructing spiro compounds by asymmetric dearomatization of indoles has become extremely promising. Meanwhile, the radical tandem reaction of unsaturated bonds has been a significant branch of organic chemistry, and this methodology has become a crucial approach to modify the indole skeleton. Therefore, the recent progress in the field of radical cascade reaction of unsaturated hydrocarbon using nitrogen heterocycle in indoles as radical acceptors is summarized. Besides, the reaction design, mechanism and prospects of this field are also discussed.

Key words: indole, radical, cascade cyclization reactions, unsaturated bonds, difunctionalization

引用此文

王弯弯, 张明明, 杨文超, 杨小虎. 吲哚氮杂环作为自由基受体在串联环化反应中的研究进展[J]. 有机化学, 2022, 42(1): 75-84.

Wanwan Wang, Mingming Zhang, Wenchao Yang, Xiaohu Yang. Research Progress in Radical Cascade Reaction Using Nitrogen Heterocycle in Indoles as Radical Acceptors[J]. Chinese Journal of Organic Chemistry, 2022, 42(1): 75-84.

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

分享此文

图/表 20

图式1. 官能化吲哚参与的自由基反应

Scheme 1. Functionalized indoles involved free radical reactions

图式2. 异腈参与的自由基反应

Scheme 2. Isocyanides involved free radical reactions

图式3. 吲哚的自由基串联与去芳构化反应

Scheme 3. Radical cascade and dearomatization of indoles

图式4. 吲哚的自由基串联与去芳构化反应

Scheme 4. Radical cascade and dearomatization of indoles

图式5. 异腈的自由基串联反应

Scheme 5. Radical cascade reaction of isocyanide

图式6. N-炔丙基吲哚与酰氯的光催化串联环化反应

Scheme 6. Visible light-catalyzed cascade radical cyclization of N-propargylindoles with acyl chlorides

图式7. N-炔丙基吲哚与α-酮酸的串联环化反应

Scheme 7. Cascade cyclization of N-propargylindoles with α-keto acids

图式8. 炔酮的三氟甲基化与吲哚的去芳构化螺环化

Scheme 8. Trifluoromethylation of ynones coupled with dearomatizing spirocyclization of indoles

图式9. 烯烃的磷酰化与环化反应

Scheme 9. Phosphinoylation and cyclization of alkenes

图式10. 烯烃的磷酰化与环化反应

Scheme 10. Phosphinoylation and cyclization of alkenes

图式11. 炔烃的磷酰化与环化反应

Scheme 11. phosphinoylation and cyclization of alkynes

图式12. 炔烃的磷酰化与环化反应

Scheme 12. Phosphinoylation and cyclization of alkynes

图式13. 炔烃的砜基化与环化反应

Scheme 13. Sulfonylation and cyclization of alkynes

图式14. N-炔丙基吲哚的砜化与环化反应

Scheme 14. Sulfonylation and cyclization of N-propargylindoles

图式15. 炔烃的硫醚化与环化反应

Scheme 15. Thioetherification and cyclization of alkynes

图式16. N-炔丙基吲哚的砜化、环化以及1,2-芳基迁移反应

Scheme 16. Sulfonylation, cyclization and 1,2-aryl migration of N-propargylindoles

图式17. N-炔丙基吲哚的硫醚化与环化反应

Scheme 17. Cascade thioetherification and cyclization of N-propargylindoles

图式18. 炔酮的硫醚化与吲哚的去芳构化螺环化

Scheme 18. Thioetherification of ynones coupled with dearomatizing spirocyclization of indoles

图式19. 炔酮的硒醚化与吲哚去芳构化螺环化

Scheme 19. Selenoetherification of ynones coupled with dearomatizing spirocyclization of indoles

图式20. 炔烃的串联环化合成磺酰化的吲哚[1,2-a]-喹啉衍生物

Scheme 20. Cascade cyclization of alkynes to access sulfonated indolo[1,2-a]-quinolones

参考文献 25

[1]	(a) Oishi, S.; Watanabe, T.; Sawada, J.; Asai, A.; Ohno, H.; Fujii, N. J. Med. Chem. 2010, 53, 5054. doi: 10.1021/jm100476d pmid: 24053617
	(b) Mahmoud, M. M.; Ali, H. I.; Ahn, K. H.; Damaraju, A.; Samala, S.; Pulipati, V. K.; Kolluru, S.; Kendall, D. A.; Lu, D. J. Med. Chem. 2013, 56, 7965. doi: 10.1021/jm4009828 pmid: 24053617
[2]	(a) Xiao, Z.; Wang, L.; Wei, J.; Ran, C.; Liang, S.; Shang, J.; Chen, G.-Y.; Zheng, C. Chem. Commun. 2020, 56, 4164. doi: 10.1039/D0CC00451K
	(b) Wang, D., https://mp.weixin.qq.com/s/U8FVSkdON-eKo7rUcu7kQw.
	(c) Shi, Z.; Nie, K.; Liu, C.; Zhang, M.; Zhang, W. Chin. J. Org. Chem. 2020, 40, 327. (in Chinese) doi: 10.6023/cjoc201907047
	(施展, 聂克睿, 刘畅, 张明智, 章维华, 有机化学, 2020, 40, 327.) doi: 10.6023/cjoc201907047
[3]	(a) Huang, G.; Yin, B. Adv. Synth. Catal. 2019, 361, 405. doi: 10.1002/adsc.v361.3
	(b) Lü, S.; Zhang, G.; Chen, J.; Gao, W. Adv. Synth. Catal. 2020, 362, 462. doi: 10.1002/adsc.v362.3
[4]	(a) Yang, W.-C.; Feng, J.-G.; Wu, L.; Zhang, Y.-Q. Adv. Synth. Catal. 2019, 361, 1700. doi: 10.1002/adsc.v361.8
	(b) Yang, W.-C.; Zhang, M.-M.; Feng, J.-G. Adv. Synth. Catal. 2020, 362, 4446. doi: 10.1002/adsc.v362.21
	(c) Shang, T.; Lu, L.; Cao, Z.; Liu, Y.; He, W.; Yu, B. Chem. Commun. 2019, 55, 5408. doi: 10.1039/C9CC01047E
	(d) Wu, Y.; Chen, J.-Y.; Li, Q.; Wei, W.-T. Chin. J. Org. Chem. 2020, 40, 589. (in Chinese) doi: 10.6023/cjoc201909032
	(吴燕, 陈锦杨, 李强, 魏文廷, 有机化学, 2020, 40, 589.) doi: 10.6023/cjoc201909032
	(e) Zhang, M.; Shen, L.; Dong, S.; Li, B.; Meng, F.; Si, W.; Yang, W. Eur. J. Org. Chem. 2021, 31, 4465.
[5]	(a) Zhang, B.; Studer, A. Chem. Soc. Rev. 2015, 44, 3505. doi: 10.1039/c5cs00083a pmid: 25882084
	(b) Lei, J.; Huang, J.; Zhu, Q. Org. Biomol. Chem. 2016, 14, 2593. doi: 10.1039/C6OB00087H pmid: 25882084
	(c) Song, B.; Xu, B. Chem. Soc. Rev. 2017, 46, 1103. doi: 10.1039/C6CS00384B pmid: 25882084
	(d) Yang, W.-C.; Wei, K.; Sun, X.; Zhu, J.; Wu, L. Org. Lett. 2018, 20, 3144. doi: 10.1021/acs.orglett.8b01278 pmid: 25882084
	(e) Liu, Y.; Chen, X.-L.; Sun, K.; Li, X.-Y.; Zeng, F.-L.; Liu, X.-C.; Qu, L.-B.; Zhao, Y.-F.; Yu, B. Org. Lett. 2019, 21, 4019. doi: 10.1021/acs.orglett.9b01175 pmid: 25882084
[6]	He, Z.; Bae, M.; Wu, J.; Jamison, T. F. Angew. Chem., Int. Ed. 2014, 53, 14451. doi: 10.1002/anie.201408522
[7]	Han, G.; Wang, Q.; Chen, L.; Liu, Y.; Wang, Q. Adv. Synth. Catal. 2016, 358, 561. doi: 10.1002/adsc.201500988
[8]	(a) Yang, W.; Yang, S.; Li, P.; Wang, L. Chem. Commun. 2015, 51, 7520. doi: 10.1039/C5CC00878F
	(b) Chen, Y.; Lu, L.-Q.; Yu, D.-G.; Zhu, C.-J.; Xiao, W.-J. Sci. China Chem. 2019, 62, 24. doi: 10.1007/s11426-018-9399-2
	(c) Liu, Y.; Lin, L.; Han, Y.; Liu, Y. Chin. J. Org. Chem. 2020, 40, 4216. (in Chinese) doi: 10.6023/cjoc202004053
	(刘洋, 林立青, 韩莹徽, 刘颖杰, 有机化学, 2020, 40, 4216.) doi: 10.6023/cjoc202004053
	(d) Yang, W.; Zhang, M.; Chen, W.; Yang, X.; Feng, J. Chin. J. Org. Chem. 2020, 40, 4060. (in Chinese) doi: 10.6023/cjoc202005039
	(杨文超, 张明明, 陈旺, 杨小虎, 冯建国, 有机化学, 2020, 40, 4060.) doi: 10.6023/cjoc202005039
	(e) He, S.-Q.; Li, H.-C.; Chen, X.-L.; Krylov, I. B.; Terent’ev, A. O. Qu, L.-B.; Yu, B. Chin. J. Org. Chem. 2021, 41, 4661. (in Chinese) doi: 10.6023/cjoc202105041
	(贺帅旗, 李昊聪, 陈晓岚, Igor B. Krylov, Alexander O. Terent'ev, 屈凌波, 於兵, 有机化学, 2021, 41, 4661.)
	(f) Yang, W.-C.; Zhang, M.-M.; Sun, Y.; Chen, C.-Y.; Wang, L. Org. Lett. 2021, 23, 6691. doi: 10.1021/acs.orglett.1c02260
[9]	Zhu, M.; Zhou, K.; Zhang, X.; You, S.-L. Org. Lett. 2018, 20, 4379. doi: 10.1021/acs.orglett.8b01899
[10]	Qin, W.-B.; Xiong, W.; Li, X.; Chen, J.-Y.; Lin, L.-T.; Wong, H. N. C.; Liu, G.-K. J. Org. Chem. 2020, 85, 10479. doi: 10.1021/acs.joc.0c00816
[11]	Liu, Y.; Chen, Z.; Wang, Q.-L.; Chen, P.; Xie, J.; Xiong, P.-Q.; Zhang, P.-L.; Tang, K.-W. J. Org. Chem. 2020, 85, 2385. doi: 10.1021/acs.joc.9b03090 pmid: 31927897
[12]	(a) Penteado, F.; Lopes, E. F.; Alves, D.; Perin, G.; Jacob, R. G.; Lenardão, E. J. Chem. Rev. 2019, 119, 7113. doi: 10.1021/acs.chemrev.8b00782 pmid: 30990680
	(b) Yang, W.-C.; Dai, P.; Luo, K.; Ji, Y.-G.; Wu, L. Adv. Synth. Catal. 2017, 359, 2390. doi: 10.1002/adsc.v359.14 pmid: 30990680
	(c) Zhu, H.-L.; Zeng, F.-L.; Chen, X.-L.; Sun, K.; Li, H.-C.; Yuan, X.-Y.; Qu, L.-B.; Yu, B. Org. Lett. 2021, 23, 2976. doi: 10.1021/acs.orglett.1c00655 pmid: 30990680
	(d) Ji, W.; Tan, H.; Wang, M.; Li, P.; Wang, L. Chem. Commun. 2016, 52, 1462. doi: 10.1039/C5CC08253F pmid: 30990680
	(e) Xu, N.; Li, P.; Xie, Z.; Wang, L. Chem.-Eur. J. 2016, 22, 2236. doi: 10.1002/chem.201504530 pmid: 30990680
	(f) Li, D.; Wang, M.; Liu, J.; Zhao, Q.; Wang, L. Chem. Commun. 2013, 49, 3640. doi: 10.1039/c3cc41188e pmid: 30990680
	(g) Reddy, C. R.; Kajareab, R. C.; Punna, N. Chem. Commun. 2020, 56, 3445. doi: 10.1039/C9CC10069E pmid: 30990680
[13]	(a) Zhang, Y.; Sun, K.; Lü, Q.; Chen, X.; Qu, L.; Yu, B. Chin. Chem. Lett. 2019, 30, 1361. doi: 10.1016/j.cclet.2019.03.034
	(b) Xu, J.; Zhang, S.; Luo, Y.; Zhang, L.; Zhang, F.; Huang, T.; Song, Q. Acta Chim. Sinica 2019, 77, 932. (in Chinese) doi: 10.6023/A19050169
	(许健, 张世樊, 罗莹, 张荔, 张帆, 黄挺菁, 宋秋玲, 化学学报, 2019, 77, 932.) doi: 10.6023/A19050169
	(c) Liu, X.-C.; Chen, X.-L.; Liu, Y.; Sun, K.; Peng, Y.-Y.; Qu, L.-B.; Yu, B. ChemSusChem 2020, 13, 298. doi: 10.1002/cssc.v13.2
[14]	Li, C.; Xue, L.; Zhou, J.; Zhao, Y.; Han, G.; Hou, J.; Song, Y.; Liu, Y. Org. Lett. 2020, 22, 3291. doi: 10.1021/acs.orglett.0c01097
[15]	(a) Luo, K.; Yang, W.-C.; Wu, L. Asian J. Org. Chem. 2017, 6, 350. doi: 10.1002/ajoc.v6.4
	(b) Jing, C.; Chen, X.; Sun, K.; Yang, Y.; Chen, T.; Liu, Y.; Qu, L.; Zhao, Y.; Yu, B. Org. Lett. 2019, 21, 486. doi: 10.1021/acs.orglett.8b03768
	(c) Zhou, Z.-Z.; Jin, D.-P.; Li, L.-H.; He, Y.-T.; Zhou, P.-X.; Yan, X.-B.; Liu, X.-Y.; Liang, Y.-M. Org. Lett. 2014, 16, 5616. doi: 10.1021/ol502397f
	(d) Li, Y.-M.; Sun, M.; Wang, H.-L.; Tian, Q.-P.; Yang, S.-D. Angew. Chem., Int. Ed. 2013, 52, 3972. doi: 10.1002/anie.v52.14
[16]	(a) Liu, J. M.; Zhao, S. S.; Song, W. W.; Li, R.; Guo, X. Y.; Zhuo, K. L.; Yue, Y. Y. Adv. Synth. Catal. 2017, 359, 609. doi: 10.1002/adsc.v359.4
	(b) Xu, J.; Yu, X.; Song, Q. Org. Lett. 2017, 19, 980. doi: 10.1021/acs.orglett.6b03713
[17]	Gorre, R.; Enagandhula, D.; Balasubramanianbc, S.; Akondi, S. M. Org. Biomol. Chem. 2020, 18, 1354. doi: 10.1039/C9OB02730K
[18]	(a) Chen, S.; Zhang, P. B.; Shu, W. Y.; Gao, Y. Z.; Tang, G.; Zhao, Y. F. Org. Lett. 2016, 18, 5712. pmid: 27779415
	(b) Zhang, H.; Li, W.; Zhu, C. J. Org. Chem. 2017, 82, 2199. doi: 10.1021/acs.joc.6b02673 pmid: 27779415
[19]	Hua, H.-L.; Zhang, B.-S.; He, Y.-T.; Qiu, Y.-F.; Wu, X.-X.; Xu, P.-F.; Liang, Y.-M. Org. Lett. 2016, 18, 216. doi: 10.1021/acs.orglett.5b03329
[20]	(a) Zhu, J.; Yang, W.-C.; Wang, X.-D.; Wu, L. Adv. Synth. Catal. 2018, 360, 386. doi: 10.1002/adsc.v360.3
	(b) Zhang, M.-M.; Sun, Y.; Wang, W.-W.; Chen, K.-K.; Yang, W.-C.; Wang, L. Org. Biomol. Chem. 2021, 19, 3844. doi: 10.1039/D1OB00079A
	(c) Zhang, P.; Gao, Y.; Chen, S.; Tang, G.; Zhao, Y. Org. Chem. Front. 2017, 4, 1350. doi: 10.1039/C7QO00167C
	(d) Xie, X.; Li, P.; Wang, L. Eur. J. Org. Chem. 2019, 221.
	(e) Chen, H.; Liu, M.; Qiu, G.; Wu, J. Adv. Synth. Catal. 2019, 361, 146. doi: 10.1002/adsc.v361.1
	(f) Zhang, P.; Shi, S.; Gao, X.; Han, S.; Lin, J.; Zhao, Y. Org. Biomol. Chem. 2019, 17, 2873. doi: 10.1039/C9OB00218A
	(g) Shen, Z.-J.; Huang, B.; Ma, N.; Yao, L.; Yang, C.; Guo, L.; Xia, W. Adv. Synth. Catal. 2021, 363, 1944. doi: 10.1002/adsc.v363.7
[21]	Zhu, J.; Sun, S.; Xia, M.; Gu, N.; Cheng, J. Org. Chem. Front. 2017, 4, 2153. doi: 10.1039/C7QO00478H
[22]	Zhu, X.-Y.; Han, Y.-P.; Li, M.; Li, X.-S.; Liang, Y.-M. Adv. Synth. Catal. 2018, 360, 3460. doi: 10.1002/adsc.v360.18
[23]	Gharpure, S. J.; Shelke, Y. G. Org. Lett. 2017, 19, 5022. doi: 10.1021/acs.orglett.7b02005 pmid: 28902520
[24]	(a) Ho, H. E.; Pagano, A.; Rossi-Ashton, J. A.; Donald, J. R.; Epton, R. G.; Churchill, J. C.; James, M. J.; O'Brien, P.; Taylor, R. J. K.; Unsworth, W. P. Chem. Sci. 2020, 11, 1353. doi: 10.1039/C9SC05311E
	(b) Zhou, X.-J.; Liu, H.-Y.; Mo, Z.-Y.; Ma, X.-L.; Chen, Y.-Y.; Tang, H.-T.; Pan, Y.-M.; Xu, Y.-L. Chem.-Asian J. 2020, 15, 1536. doi: 10.1002/asia.v15.10
[25]	Sun, K.; Chen, X. L.; Zhang, Y. L.; Li, K.; Huang, X. Q.; Peng, Y. Y.; Qu, L. B.; Yu, B. Chem. Commun. 2019, 55, 12615. doi: 10.1039/C9CC06924K