铜催化不对称炔丙基取代/环化串联反应研究进展

doi:10.6023/cjoc202605003

有机化学 ›› 2026, Vol. 46 ›› Issue (9): 3506-3522.DOI: 10.6023/cjoc202605003 上一篇下一篇

综述与进展

铜催化不对称炔丙基取代/环化串联反应研究进展

陈小龙^a^,^b, 高琳^b, 丁奎岭^a^,^b^,^c^,^*(), 王晓明^b^,^d^,^*()

^a 上海科技大学物质科学与技术学院上海 201210
^b 中国科学院上海有机化学研究所上海 200032
^c 上海交通大学化学化工学院上海 200240
^d 中国科学院大学杭州高等研究院杭州 310024

收稿日期:2026-05-06 修回日期:2026-05-22 发布日期:2026-06-03
基金资助:
国家重点研发计划(2022YFA1503200); 及中国科学院战略性先导科技专项(XDB1180000)

Progress in Copper-Catalyzed Asymmetric Propargylic Substitution/Cyclization Cascades

Xiaolong Chen^a^,^b, Lin Gao^b, Kuiling Ding^a^,^b^,^c^,^*(), Xiaoming Wang^b^,^d^,^*()

^a School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210
^b Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032
^c School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240
^d Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024

Received:2026-05-06 Revised:2026-05-22 Published:2026-06-03
Contact:
^* E-mail: kding@sioc.ac.cn;
xiaoming@sioc.ac.cn
About author:
Dedicated to the 100th anniversary of the birth of Professor Xikui Jiang.
Supported by:
National Key R&D Program of China(2022YFA1503200); Strategic Priority Research Program of the Chinese Academy of Sciences(XDB1180000)

文章分享

摘要/Abstract

铜催化不对称炔丙基取代/环化串联反应因其条件温和及对映选择性高等优势, 已成为构建手性环状化合物的重要方法之一. 该反应的关键在于生成亚丙二烯基铜中间体, 随后被双亲核试剂捕获, 进而发生串联环化, 高效构筑结构多样的手性杂环化合物. 系统总结了近年来铜催化不对称炔丙基取代/环化串联反应的研究进展.

关键词: 铜催化, 不对称炔丙基取代, 环化反应, 手性叔碳中心, 手性季碳中心

Copper-catalyzed asymmetric propargylic substitution/cyclization cascade reactions have become one of the important methods for constructing chiral cyclic compounds due to their advantages such as mild conditions and high enantioselectivity. The key to this reaction lies in the formation of a copper-allenylidene intermediate, which is subsequently captured by a bis-nucleophile, followed by cascade cyclization, enabling the efficient construction of structurally diverse chiral heterocyclic compounds. The research progress of copper-catalyzed asymmetric propargylic substitution/cyclization cascade reactions in recent years is systematically summarized.

Key words: copper catalysis, asymmetric propargylic substitution, cyclization reaction, tertiary carbon stereocenter, quaternary carbon stereocenter

引用此文

陈小龙, 高琳, 丁奎岭, 王晓明. 铜催化不对称炔丙基取代/环化串联反应研究进展[J]. 有机化学, 2026, 46(9): 3506-3522.

Xiaolong Chen, Lin Gao, Kuiling Ding, Xiaoming Wang. Progress in Copper-Catalyzed Asymmetric Propargylic Substitution/Cyclization Cascades[J]. Chinese Journal of Organic Chemistry, 2026, 46(9): 3506-3522.

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

分享此文

图/表 26

图式1. 铜催化不对称炔丙基取代/环化串联反应发展

Scheme 1. Development of copper-catalyzed asymmetric propargylic substitution/annulation cascade reactions

图式2. 铜催化的分子间与分子内的不对称炔丙基取代/环化串联反应

Scheme 2. Copper-catalyzed intermolecular and intramolecular asymmetric propargylic substitution/cyclization cascade reactions

图式3. 铜催化的不对称炔丙基酯与环状烯胺的环加成反应

Scheme 3. Copper-catalyzed asymmetric cycloaddition reaction of propargylic esters with cyclic enamines

图式4. 胡向平课题组报道的一系列铜催化的不对称炔丙基取代/环化串联反应

Scheme 4. A series of copper-catalyzed asymmetric propargylic substitution/cyclization cascade reactions reported by Hu’s group

图式5. 铜催化的三甲基硅基炔丙基乙酸酯的不对称炔丙基取代/环化串联反应

Scheme 5. Copper-catalyzed asymmetric propargylic substitution/cyclization cascade reaction of trimethylsilyl propargyl acetates

图式6. 铜催化的硫叶立德与乙炔基苯并噁嗪酮的不对称[4＋1]环加成反应

Scheme 6. Copper-catalyzed asymmetric [4＋1] cycloaddition of sulfur ylides with ethynyl benzoxazinones

图式7. 铜/胺协同催化的乙炔基苯并噁嗪酮的不对称环化反应

Scheme 7. Copper/amine cooperative catalyzed asymmetric cyclization of ethynyl benzoxazinones

图式8. 铜催化的乙炔基苯并噁嗪酮的不对称[4＋2]环加成反应

Scheme 8. Copper-catalyzed asymmetric [4＋2] cycloaddition reactions of ethynyl benzoxazinones

图式9. 铜催化的乙炔基苯并噁嗪酮的不对称[3＋3]与[4＋3]环加成反应

Scheme 9. Copper-catalyzed asymmetric [3＋3] and [4＋3] cycloaddition reactions of ethynyl benzoxazinones

图式10. 铜催化的远程对映选择性炔丙基取代/环加成串联反应

Scheme 10. Copper-catalyzed remote enantioselective propargylic substitution/cycloaddition cascade

图式11. 铜催化的炔丙酯的不对称[3＋2]环化反应

Scheme 11. Copper-catalyzed asymmetric [3＋2] cycloaddition of propargylic esters

图式12. 铜催化的不对称炔丙基胺化-羧化环化串联反应

Scheme 12. Copper-catalyzed asymmetric propargylic amination-carboxylation cyclization cascade reaction

图式13. 铜催化的分子间不对称炔丙基去芳构化反应

Scheme 13. Copper-catalyzed intermolecular asymmetric propargylic dearomatization

图式14. 铜/胺协同催化的不对称[3＋2]环加成反应

Scheme 14. Asymmetric [3＋2] cycloaddition catalyzed by copper/amine cooperative catalysis

图式15. 胡向平课题组报道的构筑手性季碳环状化合物策略

Scheme 15. Strategy reported by Hu’s group for constructing chiral cyclic compounds with quaternary carbon stereocenters

图式16. N-杂环卡宾与铜的协同催化不对称[3＋3]和[3＋4]环化反应

Scheme 16. N-Heterocyclic carbene and copper cooperative catalyzed asymmetric [3＋3] and [3＋4] cyclizations

图式17. 铜催化乙炔基吲哚噁唑烷酮与吖内酯的不对称[3＋2]环化反应

Scheme 17. Copper-catalyzed asymmetric [3＋2] annulation of ethynylindole oxazolidinones with azlactones

图式18. 铜催化乙炔基碳酸乙烯酯的不对称炔丙基取代/环加成串联反应

Scheme 18. Copper-catalyzed asymmetric propargylic substitution/cycloaddition cascade reaction of ethynyl vinyl carbonates

图式19. 铜催化的乙炔基氨基甲酸酯的不对称炔丙基取代/[3＋2]环加成串联反应

Scheme 19. Copper-catalyzed asymmetric propargylic substitution/[3＋2] cycloaddition cascade reaction of ethynyl carbamates

图式20. 铜催化不对称炔丙基胺化串联环化策略构筑季碳手性中心

Scheme 20. Copper-catalyzed asymmetric propargylic amination cascade cyclization strategy for the construction of quaternary stereocenters

图式21. 铜催化乙炔基碳酸乙烯酯的不对称[3＋3]环加成反应

Scheme 21. Copper-catalyzed asymmetric [3＋3] cycloaddition reaction of ethynylethylene carbonates

图式22. 铜催化远程对映选择性炔丙基取代构筑手性季碳环状化合物

Scheme 22. Copper-catalyzed remote enantioselective propargylic substitution for the construction of chiral cyclic compounds bearing quaternary carbon stereocenters

图式23. 手性双核铜催化不对称炔丙基化/[3＋2]环加成串联反应

Scheme 23. Chiral dinuclear copper-catalyzed asymmetric propargylation/[3＋2] cycloaddition cascade reaction

图式24. 铜催化三氟甲基取代的炔丙酯的不对称[3＋2]环加成反应

Scheme 24. Copper-catalyzed asymmetric [3＋2] cycloaddition reaction of trifluoromethyl-substituted propargyl esters

图式25. 铜催化乙炔基亚甲基环状氨基甲酸酯与二烯醇硅醚的不对称[4＋3]环加成反应

Scheme 25. Copper-catalyzed asymmetric [4＋3] cycloaddition reaction of ethynylmethylene cyclic carbamates with dienol silyl ethers

图式26. 铜催化的分子内炔丙基取代/重排或开环/环化反应

Scheme 26. Copper-catalyzed intramolecular propargylic substitution/rearrangement or ring-opening/cyclization reactions

参考文献 50

[1]	(a) Ljungdahl, N.; Kann, N. Angew. Chem., Int. Ed. 2009, 48, 642.
	(b) Miyake, Y.; Uemura, S.; Nishibayashi, Y. ChemCatChem 2009, 1, 342.
	(c) Detz, R. J.; Hiemstra, H.; van Maarseveen, J. H. Eur. J. Org. Chem. 2009, 2009, 6263.
	(d) Ding, C.-H.; Hou, X.-L. Chem. Rev. 2011, 111, 1914.
	(e) Sakata, K.; Nishibayashi, Y. Catal. Sci. Technol. 2018, 8, 12.
	(f) Roy, R.; Saha, S. RSC Adv. 2018, 8, 31129.
	(g) Tsuji, H.; Kawatsura, M. Asian J. Org. Chem. 2020, 9, 1924.
	(h) Nishibayashi, Y. Chem. Lett. 2021, 50, 1282.
	(i) Zhang, Y.-P.; You, Y.; Yin, J.-Q.; Wang, Z.-H.; Zhao, J.-Q.; Li, Q.; Yuan, W.-C. Eur. J. Org. Chem. 2023, 26, e202300728.
[2]	Detz, R. J.; Delville, M. M. E.; Hiemstra, H.; van Maarseveen, J. H. Angew. Chem., Int. Ed. 2008, 47, 3777.
[3]	Hattori, G.; Matsuzawa, H.; Miyake, Y.; Nishibayashi, Y. Angew. Chem., Int. Ed. 2008, 47, 3781.
[4]	(a) Zhang, D.-Y.; Hu, X.-P. Tetrahedron Lett. 2015, 56, 283.
	(b) Li, M.-D.; Wang, X.-R.; Lin, T.-Y. Tetrahedron Chem. 2024, 11, 100082.
[5]	Hattori, G.; Miyake, Y.; Nishibayashi, Y. ChemCatChem 2010, 2, 155.
[6]	Shibata, M.; Nakajima, K.; Nishibayashi, Y. Chem. Commun. 2014, 50, 7874.
[7]	Zhang, C.; Hu, X.-H.; Wang, Y.-H.; Zheng, Z.; Xu, J.; Hu, X.-P. J. Am. Chem. Soc. 2012, 134, 9585.
[8]	Zhu, F.-L.; Wang, Y.-H.; Zhang, D.-Y.; Xu, J.; Hu, X.-P. Angew. Chem., Int. Ed. 2014, 53, 10223.
[9]	(a) Zhang, D.-Y.; Shao, L.; Xu, J.; Hu, X.-P. ACS Catal. 2015, 5, 5026.
	(b) Chen, X.; Hou, C.; Li, Q.; Liu, Y.; Yang, R.; Hu, X. Chin. J. Catal. 2016, 37, 1389.
	(c) Liu, Z.-T.; Wang, Y.-H.; Zhu, F.-L.; Hu, X.-P. Org. Lett. 2016, 18, 1190.
	(d) Li, L.; Chen, X.-S.; Hu, X.-P. Org. Lett. 2022, 24, 5433.
[10]	Shao, L.; Wang, Y.-H.; Zhang, D.-Y.; Xu, J.; Hu, X.-P. Angew. Chem., Int. Ed. 2016, 55, 5014.
[11]	Li, L.; Liu, Z.-T.; Hu, X.-P. Chem. Commun. 2018, 54, 12033.
[12]	Wang, Q.; Li, T.-R.; Lu, L.-Q.; Li, M.-M.; Zhang, K.; Xiao, W.-J. J. Am. Chem. Soc. 2016, 138, 8360.
[13]	Song, J.; Zhang, Z.-J.; Gong, L.-Z. Angew. Chem., Int. Ed. 2017, 56, 5212.
[14]	Lu, X.; Ge, L.; Cheng, C.; Chen, J.; Cao, W.; Wu, X. Chem.-Eur. J. 2017, 23, 7689.
[15]	Zhang, Y.-C.; Zhang, Z.-J.; Fan, L.-F.; Song, J. Org. Lett. 2018, 20, 2792.
[16]	Chen, H.; Lu, X.; Xia, X.; Zhu, Q.; Song, Y.; Chen, J.; Cao, W.; Wu, X. Org. Lett. 2018, 20, 1760.
[17]	Ji, D.; Wang, C.; Sun, J. Org. Lett. 2018, 20, 3710.
[18]	(a) Jiang, F.; Feng, X.; Wang, R.; Gao, X.; Jia, H.; Xiao, Y.; Zhang, C.; Guo, H. Org. Lett. 2018, 20, 5278.
	(b) Wang, Y.; Zhu, L.; Wang, M.; Xiong, J.; Chen, N.; Feng, X.; Xu, Z.; Jiang, X. Org. Lett. 2018, 20, 6506.
[19]	Kong, H.-H.; Zhu, C.; Deng, S.; Xu, G.; Zhao, R.; Yao, C.; Xiang, H.-M.; Zhao, C.; Qi, X.; Xu, H. J. Am. Chem. Soc. 2022, 144, 21347.
[20]	Luo, D.; Niu, S.; Gong, F.; Xu, C.; Lan, S.; Liu, J.; Yang, S.; Fang, X. ACS Catal. 2024, 14, 2746.
[21]	Wang, Z.-H.; Liu, R.-X.; Liu, Y.-X.; Liu, X.-C.; Cao, K.; Lin, T.-Y. Org. Lett. 2026, 28, 1412.
[22]	Dai, X.-K.; Xiong, J.-X.; Wang, Z.-Y.; Qian, H.-D.; Zhao, J.; Zhou, S.; Xu, H. Chin. Chem. Lett. 2026, 37, 112870.
[23]	Geng, Z.-Q.; Zhao, C.; Qian, H.-D.; Li, S.-J.; Peng, H.; Xu, H. Org. Lett. 2023, 25, 4504.
[24]	Rohilla, S.; Shah, S.; Singh, V. K. Org. Lett. 2023, 25, 3733.
[25]	Li, Z.-H.; Ma, J.-S.; Lu, H.-Y.; Lin, G.-Q.; He, Z.-T. ACS Catal. 2024, 14, 11646.
[26]	Lan, Y.; Liu, P.; Fang, Z.; Shao, L.; Cai, Q.; Wang, X. Org. Chem. Front. 2024, 11, 6319.
[27]	Shao, W.; Li, H.; Liu, C.; Liu, C.-J.; You, S.-L. Angew. Chem., Int. Ed. 2015, 54, 7684.
[28]	Shao, W.; You, S.-L. Chem.-Eur. J. 2017, 23, 12489.
[29]	Zhang, Y.-C.; Zhang, B.-W.; Geng, R.-L.; Song, J. Org. Lett. 2018, 20, 7907.
[30]	Xu, Y.-W.; Hu, X.-P. Org. Lett. 2019, 21, 8091.
[31]	Xu, Y.-W.; Li, L.; Hu, X.-P. Org. Lett. 2020, 22, 9534.
[32]	Zhang, Z.-J.; Zhang, L.; Geng, R.-L.; Song, J.; Chen, X.-H.; Gong, L.-Z. Angew. Chem., Int. Ed. 2019, 58, 12190.
[33]	Zhang, J.; Ni, T.; Yang, W.-L.; Deng, W.-P. Org. Lett. 2020, 22, 4547.
[34]	Wang, M.; Li, B.; Gong, B.; Yao, H.; Lin, A. Chem. Commun. 2022, 58, 2850.
[35]	Zuo, S.; Tao, Y.; Liu, Z.; Zhang, K.; Zhang, L.; Ning, Y.; Chen, F.-E. Org. Lett. 2023, 25, 410.
[36]	Zhu, H.; Xu, L.; Zhu, B.; Liao, M.; Li, J.; Han, Z.; Sun, J.; Huang, H. Org. Lett. 2023, 25, 9213.
[37]	Wang, T.; You, Y.; Wang, Z.-H.; Zhao, J.-Q.; Zhang, Y.-P.; Yin, J.-Q.; Zhou, M.-Q.; Cui, B.-D.; Yuan, W.-C. Org. Lett. 2023, 25, 1274.
[38]	Battula, S.; Kothuri,, P.; Bhumannagari, H.; Nayani, K. Org. Biomol. Chem. 2024, 22, 1671.
[39]	(a) Zhang, Z.; Sun, Y.; Gong, Y.; Tang, D.-L.; Luo, H.; Zhao, Z.-P.; Zhou, F.; Wang, X.; Zhou, J. Nat. Chem. 2024, 16, 521.
	(b) Zhang, Z.; Zhang, Z. H.; Sun, Y.; Tang, Y. H.; Yang, Y. Z.; Zhou, F.; Zhou, J. Sci. China: Chem. 2025, 68, 1402.
[40]	Zhang, Y.; Shu, X.; Guo, W. Org. Chem. Front. 2024, 11, 1996.
[41]	Chen, P.; Zhang, M.-M.; Rao, L.; Li, Y.-H.; Jia, Y.; Tan, Y.; Xiao, W.-J.; Lu, L.-Q. Sci. Bull. 2024, 69, 3516.
[42]	(a) Xu, G.; Zhu, C.; Li, X.; Zhu, K.; Xu, H. Chin. Chem. Lett. 2025, 36, 110114.
	(b) Zhao, R.; Deng, S.; Huang, R.; Kong, H.-H.; Lu, Y.; Yin, T.; Wang, J.; Li, Y.; Zhu, C.; Pan, F.; Qi, X.; Xu, H. ACS Catal. 2024, 14, 9254.
[43]	Li, X.; Guo, J.-X.; Zhang, J.; Chen, Q.-Y.; He, Y.-J.; Sha, F.; Xiang, H.; Yu, P.; Liu, P.-N. ACS Catal. 2024, 14, 9244.
[44]	Guo, J.; He, Y.; Cheng, X.; Xiang, H.; Li, X. Org. Lett. 2025, 27, 10700.
[45]	(a) Cai, Q.; Rao, H.; Li, S.-J.; Lan, Y.; Ding, K.; Wang, X. Chem 2024, 10, 265.
	(b) Shao, L.; Fang, Z.;; Liu, P.; Lan, Y.; Cai, Q.; Wang, X. Nat. Commun. 2025, 16, 7191.
[46]	Rohilla, S.; Khan, Z. A.; Singh, V. K. Org. Biomol. Chem. 2025, 23, 2731.
[47]	Shen, L.; Lin, Z.; Guo, B.; Zi, W. Nat. Synth. 2022, 1, 883.
[48]	Gong, F.; Meng, X.; Lan, S.; Liu, J.; Yang, S.; Fang, X. ACS Catal. 2022, 12, 12036.
[49]	Zhao, Y.; Yan, H.; Jiang, Y.; Yang, J.; Su, X.; Qiao, Z.; Zhou, W.; He, L.; Qiu, H.; Zhang, M. Chem. Sci. 2024, 15, 10963.
[50]	(a) Ge, Z.; Zhu, C.; Xu, G.; Guan, S.-N.; Xu, H. Org. Lett. 2025, 27, 5632.
	(b) Liao, M.; Li, J.; Zhu, H.; Han, Z.; Zhang, Y.; Sun, J.; Huang, H. Org. Lett. 2025, 27, 4836.

铜催化不对称炔丙基取代/环化串联反应研究进展

Progress in Copper-Catalyzed Asymmetric Propargylic Substitution/Cyclization Cascades

RichHTML

PDF

可视化

摘要/Abstract

引用此文

分享此文

图/表 26

参考文献 50

相关文章 15

编辑推荐

相关统计

本文评价

[1]	黄锦龙, 肖帆, 吴慧敏, 董秀琴, 王春江. 铱催化不对称串联烯丙基化/iso-Pictet-Spengler环化反应合成手性四氢-γ-咔啉[J]. 有机化学, 2026, 46(9): 3769-3776.
[2]	李家圆, 陈品红, 刘国生. 铜催化烯丙位C—H键不对称氧化反应[J]. 有机化学, 2026, 46(9): 3630-3639.
[3]	高鑫, 张晓莹, 胡志飞, 曹鸿志. 胭脂酮酸的合成新方法[J]. 有机化学, 2026, 46(8): 3212-3218.
[4]	韩银松, 王东炜, 肖佳怡, 冯若昆. 酰胺噁唑啉导向的铜催化[2.2]对环芳烷直接C—H酰氧基化反应[J]. 有机化学, 2026, 46(8): 3147-3157.
[5]	于丰恺, 朱先进, 徐紫涵, 石凌宇, 石永佳, 李旭锋, 杨道山. 铜催化三组分反应合成含硫醚片段的三氮唑类化合物[J]. 有机化学, 2026, 46(7): 2825-2834.
[6]	高鹰鹏, 张林军, 宋基懿, 钟品勇, 刘晋彪. 铜催化2-氨基苯甲酸与异硫氰酸酯脱硫环化合成2-氨基苯并-1,3-噁嗪-4-酮[J]. 有机化学, 2026, 46(7): 2808-2815.
[7]	李凌岳, 张嘉沛, 张硕, 崔露元, 刘希功, 刘磊. 无配体铜催化四氢-β-咔啉的氧化重排反应[J]. 有机化学, 2026, 46(7): 2789-2795.
[8]	张文钰, 刘星雨, 薛琦, 李杨, 汪苇杭, 李金恒. 基于氢原子转移策略的铜催化N-氟代磺酰胺C(sp³)—H键官能团化研究进展[J]. 有机化学, 2026, 46(7): 2529-2543.
[9]	王弘毅, 周韦屹, 彭凌子, 郭昌. 铜催化的α-亚胺酯不对称烷基化反应对映选择性合成(S)-BIRT-377[J]. 有机化学, 2026, 46(7): 2779-2788.
[10]	王雷雷, 吴娟娟, 侯易, 王景和, 孙岩, 刘静, 郭佳蕾, 齐笑, 朱超, 刘强, 吕雷阳. 铜催化6-氮杂尿嘧啶与环烷烃的交叉脱氢偶联反应[J]. 有机化学, 2026, 46(7): 2770-2778.
[11]	金海瑞, 秦杰, 赵亚婷, 夏吾炯. 铜(I)促进芳香类C(sp²)—H键的硝化反应[J]. 有机化学, 2026, 46(7): 2733-2742.
[12]	刘佩雯, 叶富, 袁伟明. 可见光介导铜催化1,3-烯炔的双官能团化反应进展[J]. 有机化学, 2026, 46(7): 2563-2580.
[13]	吴际伟, 张迪, 梅睿, 周慧乔, 汪洪湖, 段小瑞, 李子荣. 电化学氧化脱氨环化反应合成喹唑啉[J]. 有机化学, 2026, 46(6): 2358-2368.
[14]	刘妍伶, 张毅涵, 陈霞, 周晓玉, 崔颖娜, 刘海龙. 铜催化的Sonogashira偶联/亲电环化构建3-(苯硒基)苯并呋喃衍生物[J]. 有机化学, 2026, 46(6): 2379-2386.
[15]	杨珊, 陈亚苏, 朱晨. 自由基介导的官能团迁移-环化构建含氮稠杂芳烃[J]. 有机化学, 2026, 46(4): 1739-1749.