钯催化吲哚-3-羧酸酯和三亚甲基甲烷的环加成去芳构化反应

doi:10.6023/cjoc202602022

有机化学

研究论文

钯催化吲哚-3-羧酸酯和三亚甲基甲烷的环加成去芳构化反应

张青霞, 谢佳豪, 顾庆^*, 游书力^*

中国科学院上海有机化学研究所金属有机化学全国重点实验室新基石实验室上海 200032

收稿日期:2026-02-27 修回日期:2026-03-21
基金资助:
国家自然科学基金(No. 22393890、上海市科学技术委员会(23JC1404500)和上海市基础研究先行区计划资助项目.

Pd-catalyzed [3+2] Cycloaddition/Dearomatization of Indole-3-carboxylates with Trimethylenemethane

Qing-Xia Zhang, Jia-Hao Xie, Qing Gu^*, Shu-Li You^*

New Cornerstone Science Laboratory, State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China

Received:2026-02-27 Revised:2026-03-21
Contact: ^*E-mail: slyou@sioc.ac.cn, qinggu@sioc.ac.cn
Supported by:
NSFC (22393890), Science and Technology Commission of Shanghai Municipality (23JC1404500) and Shanghai Pilot Program for Basic Research. S.-L.Y. acknowledges the support from New Cornerstone Science Foundation.

文章分享

1. cjoc202602022辅助材料.pdf.pdf(10063KB)

摘要/Abstract

本文发展了钯催化吲哚-3-羧酸酯和三亚甲基甲烷（TMM）给体的[3+2]环加成反应。该反应经过钯催化的去芳构化过程,高效构建了一系列取代的2,3-环戊烷并吲哚啉（产率最高达99%）。在标准反应条件下,该反应对吲哚衍生物具有良好的官能团兼容性。值得注意的是,产物可进行酯水解、N-Ts基团脱除、Sonogashira偶联反应以及酯和卤素的还原等系列衍生化转化,充分证实了该合成方法的实用性和应用潜力。

关键词: 环加成, 去芳构化, 吲哚, 钯催化, 三亚甲基甲烷

A formal [3+2] cycloaddition between indole-3-carboxylate derivatives and trimethylenemethane (TMM) donor is disclosed. The reaction proceeds smoothly in toluene at ambient conditions via a Pd-catalyzed dearomatization process, delivering a series of substituted 2,3-fused cyclopentannulated indolines (up to 99% yield). The reaction exhibits high functional group tolerance for indole derivatives under the standard conditions. Remarkably, the synthetic utility of this method was demonstrated by transformation of the products such as hydrolysis of ester, removal of Ts group, Sonogashira coupling reaction and reduction of ester and halogen.

Key words: cycloaddition, dearomatization, indole, palladium catalysis, trimethylenemethane

引用此文

张青霞, 谢佳豪, 顾庆, 游书力. 钯催化吲哚-3-羧酸酯和三亚甲基甲烷的环加成去芳构化反应[J]. 有机化学, doi: 10.6023/cjoc202602022.

Qing-Xia Zhang, Jia-Hao Xie, Qing Gu, Shu-Li You. Pd-catalyzed [3+2] Cycloaddition/Dearomatization of Indole-3-carboxylates with Trimethylenemethane[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202602022.

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

分享此文

参考文献

[1] For selected reviews, see:(a) Zhang, D.; Song, H.; Qin, Y.Acc. Chem. Res. 2011, 44, 447., (b) Kaushik, N. K.; Kaushik, N.; Attri, P.; Kumar, N.; Kim, C. H.; Verma, A. K.; Choi, E. H. Molecules 2013, 18, 6620.(c) Blaising J.; Polyak S. J.; Pecheur, E. I. Antiviral Res 2014, 107, 84. (d) Zhang M.-Z.; Chen Q.; Yang, G.-F. Eur. J. Med. Chem. 2015, 89, 421. (e) Thakur A.; Singh A.; Kaur N.; Ojha R.; Nepali, K. Bioorg. Chem. 2020, 94, 103436. (f) Nieto M. J.; Lupton, H. K. Curr. Med. Chem.2021, 28, 4828.(g) Hawash, M. Biomolecules 2022, 12, 1843.
[2] For selected reviews on dearomatization reaction, see: (a) Zhuo, C.-X.; Zheng, C.; You, S.-L. Acc. Chem. Res. 2014, 47, 2558. (b) Sun, W.; Li, G.; Hong, L.; Wang, R. Org. Biomol. Chem. 2016, 14, 2164. (c) Wu, W.-T.; Zhang, L.; You, S.-L. Chem. Soc. Rev. 2016, 45, 1570. (d) Huang, G.; Yin, B. Adv. Synth. Catal. 2018, 361, 405. (e) Sheng, F.-T.; Wang, J.-Y.; Tan, W.; Zhang, Y.-C.; Shi, F. Org. Chem. Front. 2020, 7, 3967. (f) Wang, Z. Org. Biomol. Chem. 2020, 18, 4354. (g) Zheng, C.; You, S.-L. ACS Cent. Sci. 2021, 7, 432. (h) Liu, Y.-Z.; Song, H.; Zheng, C.; You, S.-L. Nat. Synth. 2022, 1, 203. (i) Pang, M.; Chang, H.; Feng, Z.; Zhang, J. Chin. J. Org. Chem. 2023, 43, 1271 (in Chinese) (庞明杨, 常宏宏, 冯璋, 张娟, 有机化学, 2023, 43, 1271). (j) Cheng, Y.-Z.; Li, M.; Wang, R.-X.; Zhu, L.-H.; Shen, W.-J., Zou, X.-X.; Gu, Q.; You, S.-L. Progress in Chem. 2024, 36, 1785.
[3] (a) Trost B. M.; Ehmke V.; O'Keefe B. M.; Bringley, D. A. J. Am. Chem. Soc. 2014, 136,8213. For a recent example of related dearomatization, see: (b) Zeng, W.-L.; Xia, Q.; Li, C.-Q.; Wang, M.-Y.; Jin, W.-Y.; Ding, H.; Li, W.J. Am. Chem. Soc. 2024, 146, 30764.
[4] For selected examples on metal-catalyzed dearomatization reaction of 3-nitroindoles, see: (a) Awata A.; Arai, T. Angew. Chem. Int. Ed.2014, 53, 10462.(b) Zhao, J.-Q.; Zhou, M.-Q.; Wu, Z.-J.; Wang, Z.-H.; Yue, D.-F.; Xu, X.-Y.; Zhang, X.-M.; Yuan, W.-C. Org. Lett. 2015, 17, 2238.(c) Gerten A. L.; Stanley, L. M. Org. Chem. Front.2016, 3, 339.(d) Gee, Y. S.; Rivinoja, D. J.; Wales, S. M.; Gardiner, M. G.; Ryan, J. H.; Hyland, C. J. T. J. Org. Chem. 2017, 82, 13517. (e) Laugeois, M.; Ling, J.; Ferard, C.; Michelet, V.; Ratovelomanana-Vidal, V.; Vitale, M. R. Org. Lett. 2017, 19, 2266. (f) Rivinoja, D. J.; Gee, Y. S.; Gardiner, M. G.; Ryan, J. H.; Hyland, C. J. T. ACS Catal. 2017, 7, 1053. (g) Sun, M.; Zhu, Z.-Q.; Gu, L.; Wan, X.; Mei, G.-J.; Shi, F. J. Org. Chem. 2018, 83, 2341. (h) Zhang, J.-Q.; Tong, F.; Sun, B.-B.; Fan, W.-T.; Chen, J.-B.; Hu, D.; Wang, X.-W. J. Org. Chem. 2018, 83, 2882. (i) Suo, J.-J.; Liu, W.; Du, J.; Ding, C.-H.; Hou, X.-L. Chem. Asian J. 2018, 13, 959. (j) Suo, J.-J.; Du, J.; Jiang, Y.-J.; Chen, D.; Ding, C.-H.; Hou, X.-L. Chin. Chem. Lett. 2019, 30, 1512. (k) Ling, J.; Mara, D.; Roure, B.; Laugeois, M.; Vitale, M. R. J. Org. Chem. 2020, 85, 3838. (l) Xie, J.-H.; Zheng, C.; You, S.-L. Angew. Chem. Int. Ed. 2021, 60, 22184. (m) Wan, Q.; Xie, J.-H.; Zheng, C.; Yuan, Y.-F.; You, S.-L. Angew. Chem. Int. Ed. 2021, 60, 19730. (n) Pandit, S.; Pandey, V. K.; Adhikari, A. S.; Kumar, S.; Maurya, A. K.; Kant, R.; Majumdar, N. J. Org. Chem. 2023, 88, 97. (o) Dou, P.-H.; Fu, X.-H.; Chen, Y.; Ge, Z.-Z.; Zhou, M.-Q.; Wang, Z.-H.; You, Y.; Yang, L.; Zhang, Y.-P.; Zhao, J.-Q.; Yuan, W.-C. Org. Lett. 2024, 26, 3310. (p) Chen, Y.; Zhang, X.-H.; Wang, Z.-H.; Yang, L.; You, Y.; Zhao, J.-Q.; Zhou, M.-Q.; Lu, J.-H.; Yin, J.-Q.; Yuan, W.-C. Org. Lett. 2025, 27, 11776.
[5] For selected examples on organocatalyzed or metal-free catalyzed dearomatization reaction of 3-nitroindoles, see:(a) Andreini M.; De Paolis M.; Chataigner, I. Catal. Commun. 2015, 63, 15. (b) Li Y.; Tur F.; Nielsen R. P.; Jiang H.; Jensen F.; Jørgensen, K. A. Angew. Chem. Int. Ed.2016, 55, 1020.(c) Yue, D.-F.; Zhao, J.-Q.; Chen, X.-Z.; Zhou, Y.; Zhang, X.-M.; Xu, X.-Y.; Yuan, W.-C.Org. Lett. 2017, 19, 4508.(d) Liu, X.; Yang, D.; Wang, K.; Zhang, J.; Wang, R. Green Chem. 2017, 19, 82.(e) Li, K.; Goncalves, T. P.; Huang, K.-W.; Lu, Y. Angew. Chem. Int. Ed. 2019, 58, 5427. (f) Wang, H.; Zhang, J.; Tu, Y.; Zhang, J. Angew. Chem. Int. Ed. 2019, 58, 5422. (g) Mei, M.-S.; Wang, Y.-H.; Hu, Q.; Li, Q.-H.; Shi, D.-Y.; Gao, D.; Ge, G.; Lin, G.-Q.; Tian, P. Chem. Commun. 2020, 56, 10718. (h) Huang, H.; Li, Q.-Z.; Liu, Y.-Q.; Leng, H.-J.; Xiang, P.; Dai, Q.-S.; He, X.-H.; Huang, W.; Li, J.-L. Org. Chem. Front. 2020, 7, 3862. (i) Wang, H.; Hu, Q.; Wang, M.; Guo, C. iScience 2020, 23, 100840. (j) Dai, X.; Zhang, F.; Dai, L.; Lu, Y. CCS Chem. 2023, 5, 2023.
[6] For selected reviews on electron-deficient indoles, see: (a) Cerveri A.; Bandini, M. Chin. J. Chem. 2020, 38, 287. (b) Rkein B.; Bigot A.; Birbaum L.; Manneveau M.; De Paolis M.; Legros J.; Chataigner I. Chem. Commun.2021, 57, 27.(c) Wang, N.; Ren, J.; Li, K. Eur. J. Org. Chem. 2022, e202200039.(d) Wang, H.; Xie, H.; Guo, S.-M.; Duan, R.; Lin, Y.-W.; Zhang, J. Org. Chem. Front. 2026, 13, 1458.
[7] Cheng, Q.; Zhang, F.; Cai, Y.; Guo, Y.-L.; You, S.-L.Angew. Chem. Int. Ed. 2018, 57, 2134.
[8] Zhang Q.-X.; Gu Q.; You S.-L. Org. Lett.2022, 24, 8031.
[9] Zhang Q.-X.; Li Y.; Wang J.; Yang C.; Liu C.-J.; Li X.; Cheng, J.-P. Angew. Chem. Int. Ed.2020, 59, 4550.
[10] Porcu, S.; Luridiana, A.; Martis, A.; Frongia, A.; Sarais, G.; Aitken, D. J.; Boddaert, T.; Guillot, R.; Secci, F.Chem. Commun. 2018, 54, 13547.

[1]	付雪鹏, 汪建树, 陈树清, 程鸿刚, 周强辉. 钯/降冰片烯协同催化精准合成多取代吲哚[J]. 有机化学, 2026, 46(8): 3053-3067.
[2]	唐磊, 赵刚. 银催化二氟甲基取代的乙烯吲哚与偶氮二甲酸酯的不对称环加成反应[J]. 有机化学, 2026, 46(8): 3255-3267.
[3]	林艳如, 周倩, 秦景灏, 宋德威, 宋芳芳, 高媛媛, 包欢, 李飞, 姜恒, 刘澜涛. 钯催化非活化烯烃的分子内Heck/胺化反应合成螺吲哚啉[J]. 有机化学, 2026, 46(8): 3139-3146.
[4]	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.
[5]	赵凯凯, 范润奇, 林国强, 冯陈国. 叔丁基亚砜-噁唑啉配体的合成及其在钯催化不对称烯丙基烷基化反应中的应用[J]. 有机化学, 2026, 46(6): 2458-2463.
[6]	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.
[7]	贾天猛, 孙帅, 孙伟, 苏毅进. 溴化N-酰烷基吡啶、共轭炔羰基化物与醇的三组分反应合成3-烷基中氮茚: 空气作为氧化剂[J]. 有机化学, 2026, 46(6): 2387-2398.
[8]	冯凯, 贺兆波, 王震. 钯催化烯烃的不对称氢酯基化反应研究进展[J]. 有机化学, 2026, 46(5): 1897-1915.
[9]	杨鹏飞, 马雨婷, 徐婉欣, 孙雨蒙, 仰海凌. 基于硅氧键断裂的N-酰基吲哚类酰胺的脱保护[J]. 有机化学, 2026, 46(5): 2112-2120.
[10]	郭盼盼, 张雅博, 史雯赫, 陈良军, 郭冉. 胺催化靛红与联烯酸酯的加成反应合成烯炔基-3-羟基氧化吲哚[J]. 有机化学, 2026, 46(5): 2051-2058.
[11]	石嘉逸, 仝文彦, 李志铭, 王全瑞, 张俊良. Pd/Xu-Phos催化不对称碳胺化反应合成异噁唑烷的密度泛函理论(DFT)研究[J]. 有机化学, 2026, 46(5): 2044-2050.
[12]	杨丹, 李天真, 白靖宜, 张洪浩, 石枫. 可见光氧化还原催化吲哚的还原去芳构化反应[J]. 有机化学, 2026, 46(4): 1699-1712.
[13]	谈逸凡, 焦雷. 经历Pd(I)途径的钯催化自由基反应: 反应模式简述和近期进展[J]. 有机化学, 2026, 46(4): 1303-1319.
[14]	陈鑫, 王树涛, 杨文鹏, 王楚阳, 段新华, 郭丽娜. 可见光诱导铜催化螺二氢喹唑啉酮与靛红的碳碳键裂解/偶联: 一种合成3-烷基-3-羟基-2-氧化吲哚的方法[J]. 有机化学, 2026, 46(4): 1685-1698.
[15]	韦翠, 刘金秋, 邓灿, 邹宁, 周文俊. 螺芴基化合物的合成研究进展[J]. 有机化学, 2026, 46(3): 817-839.

钯催化吲哚-3-羧酸酯和三亚甲基甲烷的环加成去芳构化反应

Pd-catalyzed [3+2] Cycloaddition/Dearomatization of Indole-3-carboxylates with Trimethylenemethane

PDF

补充材料

可视化

摘要/Abstract

引用此文

分享此文

参考文献

相关文章 15

编辑推荐

相关统计

本文评价