Ruthenium(II)-catalyzed C7-H monofluoroalkenylation of indolines with gem-difluorostyrenes

doi:10.6023/cjoc202510018

Chinese Journal of Organic Chemistry Previous Articles Next Articles

Orginal Article

钌(Ⅱ)催化吲哚啉与偕-二氟烯烃的C7-H键单氟烯化反应

柏乐乐^†,a, 吴庆荣^†,a, 李子娟^a, 刘兴旺^a, 邓璐^a, 沈秋娜^a, 吴高荣^*,a

(^a赣南医科大学药学院, 赣州 341000)
(^b赣州市第五人民医院药剂科,赣州肝病研究所赣州 341000)

收稿日期:2025-10-23 修回日期:2025-11-25
基金资助:
江西省自然科学基金(No. 20252BAC200240),江西省职业早期青年科技人才培养专项项目(No.20244BCE52224)和赣南医科大学高层次人才启动基金(No.QD202406)资助项目.

Ruthenium(II)-catalyzed C7-H monofluoroalkenylation of indolines with gem-difluorostyrenes

Bai Lele, Wu Qingrong, Li Zijuan^a, Liu Xingwang^a, Deng Lu^a, Shen Qiuna^a, Wu Gaorong^*,a

(^aSchool of Pharmacy, Gannan Medical University, Ganzhou, 341000)
(^bDepartment of Pharmacy, Ganzhou Liver Institute, Ganzhou Fifth People’s Hospital, Ganzhou 341000)

Received:2025-10-23 Revised:2025-11-25
Contact: ^*E-mail: gaorongwu09@163.com
About author:^†These authors contributed equally to this work
Supported by:
Project supported by Jiangxi Provincial Natural Science Foundation (No.20252BAC200240), Early-Career Young Scientists and Technologists Project of Jiangxi Province (No.20244BCE52224) and the Start-up Funds of Gannan Medical University (No.QD202406).

1. .pdf(3360KB)

Abstract

The indoline skeleton is widely present in natural products, drugs and bioactive molecules. Introducing monofluoroalkenes into indoline is expected to develop products with medicinal value. However, the current research is only limited to the introduction of monofluoroalkenes to the highly reactive C2 position of indole compounds through transition-metal-catalyzed, and the monofluoroalkenylation at the less reactive C7 position has not been reported. Functionalization/oxidation of the C7-H bond of indolines is an effective strategy for obtaining C7-functionalized indoles. Based on this, a novel ruthenium(II)-catalyzed C7-H monofluoroalkenylation of indolines with gem-difluorostyrenes was developed. The protocol exhibited good functional group tolerance, excellent configuration exclusivity and site selectivity. In addition, the method was scale-up implementability and could efficiently obtain indole derivatives through oxidation, which offers a potential synthetic route for this structure.

Key words: ruthenium(II)-catalyzed, indolines, gem-difluorostyrenes, C7-H monofluoroalkenylation, configuration exclusivity

Cite this article

Bai Lele, Wu Qingrong, Li Zijuan, Liu Xingwang, Deng Lu, Shen Qiuna, Wu Gaorong. Ruthenium(II)-catalyzed C7-H monofluoroalkenylation of indolines with gem-difluorostyrenes[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202510018.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1](a) Kochanowska-Karamyan A. J.; Hamann, M. T. Chem. Rev.2010, 110, 4489. (b) Baidilov D.; Elkin P. K.; Athe S.; Rawal, V. H. J. Am. Chem. Soc.2023, 145, 14831.(c) Takahashi, S.; Usui, S.; Hashida, N.; Kubota, H.; Nishida, K.; Sakaguchi, H.; Nishida, K. BMC Ophthalmol. 2021, 21, 386., 1001 (in Chinese). (段德河, 殷勤, 王守国, 顾庆, 游书力, 化学学报, 2014, 72#, 1001).
[2](a) Hande A. E.; Prabhu, K. R. J. Org. Chem.2017, 82, 13405.(b) Flynn, K. M.; White, K. L.; Movassaghi, M. J. Org. Chem. 2022, 87, 2975. (c) Xiong D.; Wang L.; Jie L.; Yang Z.; Li L.; Cui X. ChemistrySelect2018, 3, 13497.(d) Xie, G.; Zhao, Y.; Cai, C.; Deng, G.; Gong, H. Org. Lett. 2021, 23, 410., 1022.
[3](a) Furuya, T.; Kamlet, A. S.; Ritter, T.Nature 2011, 473, 470.(b) Hu, J.-B. Acta Chim. Sinica 2024, 82, 103(in Chinese). (胡金波, 化学学报, 2024, 82, 103).
[4](a) Shi, T.-T.; Li, J.; Yin, Y.-F.; Sun, K.Acta Chim. Sinica 2025, DOI: 10.6023/A25070258(in Chinese). (史同同, 李佳, 殷一樊, 孙凯,化学学报, 2025, DOI: 10.6023/A25070258). (b) Dong, Z.; Zhang, J.; Zhu. L.; Fan, X.; Liu, Z.; Yan, Y.; Kong, L. Chin. Chem. Lett. #2025, 36#, 109773.
[5](a) Jagtap R. A.; Samal P. P.; Vinod C. P.; Krishnamurty S.; Punji B. ACS Catal.2020, 10, 7312. (b) Verma S. K.; Punji, B. Chem Asian J.2022, 17, e202200103.(c) Zhai, W.-C.; Li, B.; Wang, B.-Q. ChemistrySelect 2018, 3, 8035., 493.
[6](a) Zhang L.-L.; Deng K.-Z.; Wu G.-R.; Yang J.-Y.; Tang S.-B.; Fu X.-P.; Xia C.-C.; Ji, Y.-F. J. Org. Chem.2020, 85, 12670.(b) Tian, P.; Feng, C.; Loh, T. Nat. Commun. 2015, 6, 7472. (c) Li, N.; Chang, J.-B.; Kong, L.-H.; Li, X.-W.Org. Chem. Front. 2018, 5, 1978.(d) Hong, Z.; Xiao, S.; Yang, K.; Xia, J.; Liu, X.; Shan, S.; Wu, G. Acta Chim. Sinica 2025, DOI: 10.6023/A25060237 (in Chinese). (洪朝国,肖顺丽, 杨凯, 夏家涛, 刘兴旺, 单申, 吴高荣, 化学学报#, 2025, DOI:10.6023/A25060237)
[7](a) Ji W.-W.; Lin E.; Li Q.-J.; Wang H.-G. Chem. Commun.2017, 53, 5665. (b) Wu J.-Q.; Zhang S.-S.; Gao H.; Qi Z.-S.; Zhou C.-J.; Ji W.-W.; Liu Y.; Chen Y.-Y.; Li Q.-J.; Li X.-W.; Wang, H.-G. J. Am. Chem. Soc.2017, 139, 3537.(c) Jakobsche, C. E.; Peris, G.; Miller, S. J. Angew. Chem., Int. Ed. 2008, 47, 6707.
[8](a) Kong L.-H.; Zhou X.-K.; Li X.-W. Org. Lett.2016, 18, 6320. (b) Zell D.; Müller V.; Dhawa U.; Bursch M.; Presa R. R.; Grimme S.; Ackermann, L. Chem.-Eur. J. 2017, 23, 12145. (c) Zell D.; Dhawa U.; Müller V.; Bursch M.; Grimme S.; Ackermann L. ACS Catal.2017, 7, 4209.(d) Cai, S.-H.; Ye, L.; Wang, D.-X.; Wang, Y.-Q.; Lai, L.-J.; Zhu, C.; Feng, C.; Loh, T.-P. Chem. Commun. 2017, 53, 8731.
[9](a) Wu, G.; Liu, Y.; Chen, W.; Huang, J.; Chen, X.; Wu, Q.; Huang, H.J. Org. Chem. 2024, 89, 17453.(b) Wu, G.; Ma, T. Chin. Chem. Lett. 2025, DOI: 10.1016/j.cclet.2025.111739.

[1]	Xiu-Xiu Qiao, Qian Li, Shi'na Zhao, Ruiqi Wei, Tao Ma, Yong-Hui He, Xiao-Jing Zhao. Research Progress in Asymmetric Synthesis of C2 Chiral Indolin-3-ones Involving 2-Substituted-3H-indol-3-ones [J]. Chinese Journal of Organic Chemistry, 2025, 45(4): 1166-1177.
[2]	Xueying Yang, Yuanshuang Xu, Xinying Zhang, Xuesen Fan. Synthesis of C2-Spiroindolines Based on the Cascade Reaction of 2-Aryl-3H-indoles with Cyclopropanols [J]. Chinese Journal of Organic Chemistry, 2025, 45(2): 694-706.
[3]	Yan Jin, Hongwen Mu, Yuhong Sun, Liming Wang, Ying Jin. Cinchona Alkaloid Derivative Organocatalyzed Enantioselective Cascade Knoevenagel/Michael/Cyclization of Three-Components [J]. Chinese Journal of Organic Chemistry, 2025, 45(12): 4443-4452.
[4]	Yiming Hu, Jiayu Xu, Min Tang, Yawen Liu, Liping Guan, Qinghao Jin. Design, Synthesis and Biological Activity Studies of 2-(1,3-Dioxoiso-indolin-2-yl)-N-phenethylacetamide and 2-(3,4-Dihydroisoquinolin-1-yl)isoindole-1,3-dione as Monoamine Oxidase (MAO) and Cholinesterase (ChE) Inhibitors [J]. Chinese Journal of Organic Chemistry, 2024, 44(6): 1907-1919.
[5]	Hao Ye, Haibin Zhang, Ya'nan Wu, Xinxing Wu. Research Progress in the Synthesis of Azaindoline and Its Derivatives [J]. Chinese Journal of Organic Chemistry, 2024, 44(4): 1106-1123.
[6]	Yuying Liu, Zhanwei Fu, Chao Yang, Mupeng Luo, Shurong Ban, Shouguo Wang. Rh(III)-Catalyzed Aminoalkylation of Alkenes with Diazo Compounds toward Functionalized Isoindolinones [J]. Chinese Journal of Organic Chemistry, 2024, 44(11): 3505-3517.
[7]	Yanbo Zhang, Meng Sun. Rh(III)-Catalyzed C(7)—H Formylmethylation of Indoline with Vinylene Carbonate [J]. Chinese Journal of Organic Chemistry, 2023, 43(8): 2905-2912.
[8]	Liping Pang, Changjie Yang, Hongmin Lin, Xinyu Li, Haitao Tang, Yingming Pan. Porous Organophosphine Ligand Polymers as Recyclable Ligands for the Synthesis of Isoindolinone Compounds [J]. Chinese Journal of Organic Chemistry, 2022, 42(7): 2117-2123.
[9]	Weiqing Ma, Ying Han, Jin Sun, Chaoguo Yan. Three-Component Reaction for Efficient Synthesis of Functionalized Spiro[cyclopentane-1,3'-indolines] [J]. Chinese Journal of Organic Chemistry, 2021, 41(8): 3180-3191.
[10]	Hao Tang, Beibei Zhang, Weidong Chen, Junfei Luo. A Mild and Efficient Catalytic Aerobic Oxidative Dehydrogenation of N-Pyridylindolines [J]. Chinese Journal of Organic Chemistry, 2021, 41(3): 1131-1137.
[11]	Li Wenlan, Sun Yitong, Yao Yongchao, Xu Ying, Li Peng, Liu Yingjie, Liang Deqiang. Synthesis of Polychloromethyl-Containing Indolines via Metal-Free Radical Arylpolychloromethylation of Unactivated Alkenes [J]. Chin. J. Org. Chem., 2019, 39(6): 1727-1734.
[12]	Hao Yunpeng, Xie Zhengfeng, Bao Wanrui, Wang Xin, Shi Wei. Synthesis and Properties of a Novel Colorimetric and Fluorescent Turn-On Sensor for Cyanide [J]. Chin. J. Org. Chem., 2018, 38(8): 2109-2115.
[13]	Zhang Qianqian, Ding Qunshan, Song Chuanjun, Chang Junbiao. Asymmetric Synthesis of Methyl N-(tert-Butoxycarbonyl)indoline-2-carboxylates [J]. Chin. J. Org. Chem., 2018, 38(1): 221-227.
[14]	Chen Yanchi, Ren Yujie. Synthesis and Leukemia Cell Line K562 Inhibitory Activities of α-(Fluoro-substituted isoindolinone-2-yl)glutarimide Analogues [J]. Chin. J. Org. Chem., 2015, 35(5): 1123-1130.
[15]	Xie Weiqing, Zuo Zhiwei, Zi Weiwei, Ma Dawei. Intramolecular Oxidative Coupling: Applications in Synthesis of Complex Indole Akaloid Scaffolds [J]. Chin. J. Org. Chem., 2013, 33(05): 869-876.

钌(Ⅱ)催化吲哚啉与偕-二氟烯烃的C7-H键单氟烯化反应

Ruthenium(II)-catalyzed C7-H monofluoroalkenylation of indolines with gem-difluorostyrenes

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments