配体接力促进的钯催化卡宾插入/Tsuji-Trost串联反应实现不对称[4+1]环化构筑手性茚满

doi:10.6023/cjoc202603004

有机化学 ›› 2026, Vol. 46 ›› Issue (6): 2431-2441.DOI: 10.6023/cjoc202603004 上一篇下一篇

研究论文

配体接力促进的钯催化卡宾插入/Tsuji-Trost串联反应实现不对称[4+1]环化构筑手性茚满

张超^a, 罗洲^b, 赵申^b, 沈安^c^,^*(), 杨国强^b^,^*(), 刘媛媛^a^,^*()

^a 华东师范大学化学与分子工程学院上海 200062
^b 上海交通大学变革性分子前沿科学中心上海 200240
^c 上海化工研究院聚烯烃催化技术与高性能材料全国重点实验室上海 200062

收稿日期:2026-03-04 修回日期:2026-03-20 发布日期:2026-04-02
基金资助:
国家自然科学基金(22371073); 中央高校基本科研业务费专项资金(25X010202131); 聚烯烃催化技术与高性能材料全国重点实验室(SKLZX-2025-11)

Constructing Chiral Indanes by a Ligand Relay-Enabled Pd-Catalyzed Asymmetric [4+1] Annulation via Carbene Insertion/Tsuji-Trost Cascade

Chao Zhang^a, Zhou Luo^b, Shen Zhao^b, An Shen^c^,^*(), Guoqiang Yang^b^,^*(), Yuanyuan Liu^a^,^*()

^a School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062
^b Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai 200240
^c State Key Laboratory of Polyolefins and Catalysis, Shanghai Research Institute of Chemical Industry Co., Ltd., Shanghai 200062

Received:2026-03-04 Revised:2026-03-20 Published:2026-04-02
Contact: * E-mail: yyliu@chem.ecnu.edu.cn;gqyang@sjtu.edu.cn;shenan@srici.cn
Supported by:
National Natural Science Foundation of China(22371073); Fundamental Research Funds for the Central Universities(25X010202131); State Key Laboratory of Polyolefins and Catalysis(SKLZX-2025-11)

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摘要/Abstract

经历钯-卡宾中间体的不对称环化反应为构建手性环状骨架提供了高效途径, 但其发展仍面临重大挑战. 本研究报道了一种钯催化的不对称[4+1]环化反应, 利用动态多配体接力不对称催化策略, 成功构建手性茚满类化合物. 该配体接力体系采用双齿Pyrox配体促进氧化加成步骤, 同时使用单齿Feringa型磷酰胺配体促进卡宾化/迁移插入过程及后续分子内Tsuji-Trost反应.

关键词: 不对称催化, 配体接力, 钯催化, Tsuji-Trost反应, 卡宾插入

Asymmetric annulation via palladium-carbene intermediates offers a powerful route to chiral cyclic frameworks, yet its development remains a significant challenge. Here, a Pd-catalyzed asymmetric [4+1] annulation for constructing chiral indanes is disclosed, enabled by a novel dynamic multiligand relay asymmetric catalysis. The ligand relay system employs a bidentate Pyrox ligand to promote the oxidative addition, while a monodentate Feringa-type phosphoramidite ligand facilitates the carbenation/migratory insertion step and the following intramolecular Tsuji-Trost reaction. The practical utility of this method was confirmed through a scale-up experiment. This strategy establishes a practical and efficient route to enantioenriched vicinal substituted indanes.

Key words: asymmetric catalysis, ligand relay, palladium catalysis, Tsuji-Trost reaction, carbene insertion

引用此文

张超, 罗洲, 赵申, 沈安, 杨国强, 刘媛媛. 配体接力促进的钯催化卡宾插入/Tsuji-Trost串联反应实现不对称[4+1]环化构筑手性茚满[J]. 有机化学, 2026, 46(6): 2431-2441.

Chao Zhang, Zhou Luo, Shen Zhao, An Shen, Guoqiang Yang, Yuanyuan Liu. Constructing Chiral Indanes by a Ligand Relay-Enabled Pd-Catalyzed Asymmetric [4+1] Annulation via Carbene Insertion/Tsuji-Trost Cascade[J]. Chinese Journal of Organic Chemistry, 2026, 46(6): 2431-2441.

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图/表 6

Scheme 1. Pd-catalyzed 3FGC via metal carbenes

Figure 1. Representative natural products and drugs bearing chiral indane skeletons

Without L2

With L1a

Table 1. Ligand screening a

Table 2. Substrate scopea

Scheme 2. Gram-scale reaction and derivatization of product 3a

Scheme 3. Proposed catalytic cycle

参考文献 59

[1]	Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides, Wiley, New York, 1998.
[2]	Doyle, M. P.; Forbes, D. C. Chem. Rev. 1998, 98, 911. doi: 10.1021/cr940066a
[3]	Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B. Chem. Rev. 2003, 103, 977. doi: 10.1021/cr010007e
[4]	Qi, X.; Lan, Y. Acc. Chem. Res. 2021, 54, 2905. doi: 10.1021/acs.accounts.1c00075
[5]	Davies, H. M. L.; Morton, D. Chem. Soc. Rev. 2011, 40, 1857. doi: 10.1039/c0cs00217h pmid: 21359404
[6]	Ford, A.; Miel, H.; Ring, A.; Slattery, C. N.; Maguire, A. R.; McKervey, M. A. Chem. Rev. 2015, 115, 9981. doi: 10.1021/acs.chemrev.5b00121
[7]	Zhou, G.; Guo, Z.; Shen, X. Angew. Chem. Int. Ed. 2023, 62, e202217189.
[8]	Liu, M.; Uyeda, C. Angew. Chem. Int. Ed. 2024, 63, e202406218.
[9]	Zhang, X.; Sivaguru, P.; Pan, Y.; Wang, N.; Zhang, W.; Bi, X. Chem. Rev. 2025, 125, 1049. doi: 10.1021/acs.chemrev.4c00742
[10]	Jiang, J.-X.; Liu, Q.-Z. Chin. J. Org. Chem. 2024, 44, 2640. doi: 10.6023/cjoc202401018
[11]	Guo, J.; Li, C.; Hu, R.; Rong, H.; Li, J.; Du, Y.; Qin, Y.; Lv, J.; Sun, D. Chin. J. Org. Chem. 2026, 46, 379. doi: 10.6023/cjoc202507041
[12]	Nozaki, H.; Moriuti, S.; Takaya, H.; Noyori, R. Tetrahedron Lett. 1966, 7, 5239. doi: 10.1016/S0040-4039(01)89263-7
[13]	Nozaki, H.; Takaya, H.; Moriuti, S.; Noyori, R. Tetrahedron. 1968, 24, 3655. doi: 10.1016/S0040-4020(01)91998-2
[14]	Noyori, R.; Takaya, H.; Nakanisi, Y.; Nozaki, H. Can. J. Chem. 1969, 47, 1242. doi: 10.1139/v69-202
[15]	Guo, X.; Hu, W. Acc. Chem. Res. 2013, 46, 2427. doi: 10.1021/ar300340k
[16]	Zhang, D.; Hu, W. Chem. Rec. 2017, 17, 739. doi: 10.1002/tcr.v17.8
[17]	Davies, H. M. L.; Lian, Y. Acc. Chem. Res. 2012, 45, 923. doi: 10.1021/ar300013t
[18]	Yada, A.; Fujita, S.; Murakami, M. J. Am. Chem. Soc. 2014, 136, 7217. doi: 10.1021/ja502229c
[19]	Zhang, Z.; Sheng, Z.; Yu, W.; Wu, G.; Zhang, R.; Chu, W.-D.; Zhang, Y.; Wang, J. Nat. Chem. 2017, 9, 970. doi: 10.1038/nchem.2789
[20]	Wang, K.; Li, S.-S.; Wang, J. Chem.-Eur. J. 2022, 28, e202200170.
[21]	Huo, J.; Zhong, K.; Xue, Y.; Lyu, M.; Ping, Y.; Ouyang, W.; Liu, Z.; Lan, Y.; Wang, J. Chem.-Eur. J. 2022, 28, e202200191.
[22]	Huo, J.; Zhong, K.; Xue, Y.; Lyu, M.; Ping, Y.; Liu, Z.; Lan, Y.; Wang, J. J. Am. Chem. Soc. 2021, 143, 12968. doi: 10.1021/jacs.1c05879
[23]	Xiao, Q.; Zhang, Y.; Wang, J. Acc. Chem. Res. 2013, 46, 236. doi: 10.1021/ar300101k
[24]	Xia, Y.; Qiu, D.; Wang, J. Chem. Rev. 2017, 117, 13810. doi: 10.1021/acs.chemrev.7b00382
[25]	Chu, W.-D.; Zhang, L.; Zhang, Z.; Zhou, Q.; Mo, F.; Zhang, Y.; Wang, J. J. Am. Chem. Soc. 2016, 138, 14558. doi: 10.1021/jacs.6b09674
[26]	Chu, W.-D.; Guo, F.; Yu, L.; Hong, J.; Liu, Q.; Mo, F.; Zhang, Y.; Wang, J. Chin. J. Chem. 2018, 36, 217. doi: 10.1002/cjoc.v36.3
[27]	Feng, J.; Li, B.; He, Y.; Gu, Z. Angew. Chem. Int. Ed. 2016, 55, 2186. doi: 10.1002/anie.201509571 pmid: 26745748
[28]	Zhang, H.; Lu, C.-J.; Cai, G.-H.; Xi, L.-L.; Feng, J.; Liu, R.-R. Nat. Commun. 2024, 15, 3353. doi: 10.1038/s41467-024-47731-5 pmid: 38637535
[29]	Zhao, G.; Wu, Y.; Wu, H.-H.; Yang, J.; Zhang, J. J. Am. Chem. Soc. 2021, 143, 17983. doi: 10.1021/jacs.1c09742
[30]	Zhu, S.; Xiao, B.; Huang, M.; Wu, Y.; Sun, T.-Y.; Yang, J.; Wu, Y.-D.; Zhang, J. J. Am. Chem. Soc. 2025, 147, 45210. doi: 10.1021/jacs.5c14810
[31]	Yang, B.; Cao, K.; Zhao, G.; Yang, J.; Zhang, J. J. Am. Chem. Soc. 2022, 144, 15468. doi: 10.1021/jacs.2c07037 pmid: 35994322
[32]	Sun, Y.; Ma, C.; Li, Z.; Zhang, J. Chem. Sci. 2022, 13, 11150. doi: 10.1039/D2SC03999K
[33]	Wang, X.; Wang, C.; Luo, Y.; Li, J.; Gan, C.; Luo, S.; Zhu, Q. Chem. Catal. 2024, 4, 100904.
[34]	Ning, X.; Zhao, T.; Zhu, Y.; Liu, B.; Yan, X.; Xia, Y. J. Am. Chem. Soc. 2025, 147, 16773. doi: 10.1021/jacs.5c04354
[35]	Liu, J.-G.; Chen, W.-W.; Gu, C.-X.; Xu, B.; Xu, M.-H. Org. Lett. 2018, 20, 2728. doi: 10.1021/acs.orglett.8b00935
[36]	Sun, Y.; Wang, B.; Lu, Z. Org. Chem. Front. 2023, 10, 4146. doi: 10.1039/D3QO00913K
[37]	Li, H.; Ma, B.; Liu, Q.-S.; Wang, M.-L.; Wang, Z.-Y.; Xu, H.; Li, L.-J.; Wang, X.; Dai, H.-X. Angew. Chem., Int. Ed. 2020, 59, 14388. doi: 10.1002/anie.v59.34
[38]	Trost, B. M.; Krische, M. J. J. Am. Chem. Soc. 1996, 118, 233. doi: 10.1021/ja953060r
[39]	Chen, M. S.; Narayanasamy, P.; Labenz, N. A.; White, M. C. J. Am. Chem. Soc. 2005, 127, 6970. doi: 10.1021/ja0500198
[40]	Chen, G.; Zhuang, Z.; Li, G.-C.; Saint-Denis, T. G.; Hsiao, Y.; Joe, C. L.; Yu, J.-Q. Angew. Chem. Int. Ed. 2017, 56, 1506. doi: 10.1002/anie.v56.6
[41]	Liu, L.-Y.; Qiao, J. X.; Yeung, K.-S.; Ewing, W. R.; Yu, J.-Q. Angew. Chem. Int. Ed. 2020, 59, 13831. doi: 10.1002/anie.v59.33
[42]	Sak, M. H.; Liu, R. Y.; Kwan, E. E.; Jacobsen, E. N. Nature 2025, 648, 333. doi: 10.1038/s41586-025-09813-2
[43]	Huang, W.; Xi, Y.; Pan, D.; Fan, L.; Fang, K.; Huang, G.; Zhu, W.-H.; Qu, J.; Chen, Y. J. Am. Chem. Soc. 2024, 146, 16892. doi: 10.1021/jacs.4c05480
[44]	Fan, L.; Xi, Y.; Gu, H.; Huang, W.; Zhu, W.-H.; Qu, J.; Chen, Y. Nat. Commun. 2026, 17, 1247. doi: 10.1038/s41467-025-68006-7
[45]	Luo, Z.; Zhang, Y.-H.; Zhang, C.; Dong, K.; Pramanick, P. K.; Zhao, S.; Liu, Y.; Yang, G. J. Am. Chem. Soc. 2026, 148, 4605. doi: 10.1021/jacs.5c20265
[46]	Arunprasath, D.; Muthupandi, P.; Sekar, G. Org. Lett. 2015, 17, 5448. doi: 10.1021/acs.orglett.5b02803 pmid: 26501560
[47]	Paraja, M.; Pérez-Aguilar, M. C.; Valdés, C. Chem. Commun. 2015, 51, 16241. doi: 10.1039/C5CC06348E
[48]	Borie, C.; Ackermann, L.; Nechab, M. Chem. Soc. Rev. 2016, 45, 1368. doi: 10.1039/C5CS00622H
[49]	Uchikawa, O.; Fukatsu, K.; Tokunoh, R.; Kawada, M.; Matsumoto, K.; Imai, Y.; Hinuma, S.; Kato, K.; Nishikawa, H.; Hirai, K.; Miyamoto, M.; Ohkawa, S. J. Med. Chem. 2002, 45, 4222. pmid: 12213063
[50]	Ye, Y.-Y.; Zhou, P.-X.; Luo, J.-Y.; Zhong, M.-J.; Liang, Y.-M. Chem. Commun. 2013, 49, 10190. doi: 10.1039/c3cc45583a
[51]	Trost, B. M.; Mata, G. Acc. Chem. Res. 2020, 53, 1293. doi: 10.1021/acs.accounts.0c00152
[52]	Li, Y.-L.; Zhang, P.-C.; Wu, H.-H.; Zhang, J.-L. J. Am. Chem. Soc. 2021, 143, 13010. doi: 10.1021/jacs.1c07212
[53]	Xiao, L.; Xiong, Q.; Xu, H.; Wang, Z.; Chang, X.; Dang, Y.; Dong, X.-Q.; Wang, C.-J. CCS Chem. 2025, 7, 1112. doi: 10.31635/ccschem.024.202404224
[54]	Wang, J.; Xu, B.; Wang, Y.; Xia, G.; Zhang, Z.-M.; Zhang, J. J. Am. Chem. Soc. 2024, 146, 21231. doi: 10.1021/jacs.4c07382
[55]	Liu, Y.; Li, C.; Zhang, R.; Liu, Z.; Han, Z.; Wang, Z.; Ding, K. CCS Chem. 2024, 6, 2607. doi: 10.31635/ccschem.024.202403855
[56]	Li, P.; Sun, S.; Wei, L.; Zi, W. Wang, C.-J.; Zhang, W. CCS Chem. 2026, 8, 81. doi: 10.31635/ccschem.025.202506468
[57]	Zhang, J.; He, Z. Chin. J. Org. Chem. 2025, 45, 592. doi: 10.6023/cjoc202406047
[58]	Pramanick, P. K.; Zhao, S.; Ji, H.-T.; Chen, X.; Yang, G. Angew. Chem. Int. Ed. 2025, 64, e202415927.
[59]	Zhao, S.; Ling, Z.; Xia, S.; Luo, D.; Liang, J.; Qian, L.; Wang, Z.; Li, N.; Huo, X.; Zhang, J.; Zhang, W.; Yang, G. CCS Chem. 2026, doi: 10.31635/ccschem.026.202507061

配体接力促进的钯催化卡宾插入/Tsuji-Trost串联反应实现不对称[4+1]环化构筑手性茚满

Constructing Chiral Indanes by a Ligand Relay-Enabled Pd-Catalyzed Asymmetric [4+1] Annulation via Carbene Insertion/Tsuji-Trost Cascade

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