钯催化多米诺Heck/分子间偶联反应合成3-烷基取代茚衍生物

doi:10.6023/cjoc202407029

摘要/Abstract

茚衍生物是多种天然产物及药物的核心骨架之一, 在医药、材料等领域具有广泛的应用前景. 开发简单、高效地合成茚衍生物的方法具有重要意义. 本工作以邻位链接非活化烯烃的碘苯为原料, 在钯催化下经分子内Heck反应生成烷基钯(II)中间体, 该中间体诱导2-(2-苯乙炔基)苯基丙二酸二乙酯发生分子内亲核环化, 合成了多种3-烷基取代茚衍生物. 该方法具有条件温和、操作简单、产率高、底物适用性广等优点, 为合成茚衍生物提供了一种新策略.

关键词: 钯催化, 茚衍生物, Heck反应

Indene derivatives are one of the core skeletons of many natural products and drugs, and are widely used in medicine, materials and other fields. It is of great significance to develop a simple and efficient method for the synthesis of indene derivatives. In this work, iodobenzenes with proximity linking unactivated olefins undergo palladium-catalyzed intramolecular Heck reaction to generate alkylpalladium(II) intermediates, which induce the intramolecular nucleophilic cyclization of 2-(2-phenylethynyl)phenylmalonate diethyl ester to afford a series of 3-alkyl substituted indene derivatives. The reaction has the advantages of mild conditions, simple operation, high yield and wide applicability of substrates, which provides a new strategy for the synthesis of indene derivatives.

Key words: palladium catalysis, indene derivatives, Heck reaction

引用此文

姚团利, 王琳琳, 李涛. 钯催化多米诺Heck/分子间偶联反应合成3-烷基取代茚衍生物[J]. 有机化学, 2025, 45(4): 1342-1351.

Tuanli Yao, Linlin Wang, Tao Li. Palladium-Catalyzed Domino Heck/Intermolecular Cross Coupling Reaction for the Synthesis of 3-Alkyl Substituted Indene Derivatives[J]. Chinese Journal of Organic Chemistry, 2025, 45(4): 1342-1351.

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参考文献 49

[1]	Herdman, C. A.; Strecker, T. E.; Tanpure, R. P.; Chen, Z.; Winters, A.; Gerberich, J.; Liu, L.; Hamel, E.; Mason, R. P.; Chaplin, D. J.; Trawick, M. L.; Pinney, K. G. MedChemComm 2016, 7, 2418.
[2]	Tu, S.; Xu, L. H.; Ye, L. Y.; Wang, X.; Sha, Y.; Xiao, Z. Y. J. Agric. Food Chem. 2008, 56, 5247.
[3]	Dai, l. Y.; Li, Q.; He, D.; Wang, X. Z.; Chen, Y. Q. J. Chem. Eng. Chin. Univ. 2009, 23, 673 (in Chinese).
	(戴立言, 李倩, 贺电, 王晓钟, 陈英奇, 高校化学工程学报, 2009, 23, 673.)
[4]	Gardner, S. H.; Hawcroft, G.; Hull, M. A. Br. J. Cancer 2004, 91, 153.
[5]	Branch, S. K.; Casy, A. F.; Hussain, R.; Upton, C. J. Pharm. Pharmacol. 1988, 40, 83. pmid: 2896790
[6]	Witek, T. J.; Canestrari, D. A.; Miller, R. D.; Yang, J. Y.; Riker, D. K. J. Allergy Clin. Immunol. 1992, 90, 953.
[7]	Sega, R.; Mailland, F.; Damiani, E.; Groothold, G.; Libretti, A. Clin. Pharmacol. Ther. 1983, 33, 289. pmid: 6337761
[8]	Li, B. W.; Zhang, Z. Y.; Zou, Q. Mater. Rep. 2017, 31, 67 (in Chinese).
	(李保卫, 张志云, 邹祺, 材料导报, 2017, 31, 67.)
[9]	Cao, T. T.; Chen, N.; Liu, G. X.; Wan, Y. B.; Perea, J. D.; Xia, Y. J.; Wang, Z. W.; Song, B.; Li, N.; Li, X. H.; Zhou, Y.; Brabec, C. J.; Li, Y. F. J. Mater. Chem. A 2017, 5, 10206.
[10]	Eom, D.; Park, S.; Park, Y.; Ryu, T.; Lee, P. H. Org. Lett. 2012, 14, 5392.
[11]	Bu, X. L.; Hong, J. Q.; Zhou, X. G. Adv. Synth. Catal. 2011, 353, 2111.
[12]	Khwaja, S.; Fatima, K.; Mishra, D.; Babu, V.; Kumar, Y.; Malik, S. B.; Tabassum, M.; Luqman, S.; Bawankule, D. U.; Chanda, D.; Khan, F.; Mondhe, D. M.; Negi, A. S. Chem. Biol. Drug Des. 2021, 98, 127.
[13]	Liu, C. R.; Yang, F. L.; Jin, Y. Z.; Ma, X. T.; Cheng, D. J.; Li, N.; Tian, S. K. Org. Lett. 2010, 12, 3832.
[14]	Trost, B. M.; Tracy, J. S.; Yusoontom, T.; Hung, C. J. Angew. Chem., Int. Ed. 2020, 59, 2370.
[15]	Wang, X. C.; Zhong, M. J.; Liang, Y. M. Org. Biomol. Chem. 2012, 10, 3636.
[16]	Zhao, J. B.; Clark, D. A. Org. Lett. 2012, 14, 1668.
[17]	Sun, Y.; Pan, J. Y.; Wang, X. Q.; Bu, X. L.; Ma, M. T.; Xue, F. J. Org. Chem. 2023, 88, 6140. doi: 10.1021/acs.joc.2c02957 pmid: 37019474
[18]	Tudjarian, A. A.; Minehan, T. G. J. Org. Chem. 2011, 76, 3576. doi: 10.1021/jo200271s pmid: 21405013
[19]	Dethe, D. H.; Murhade, G. Org. Lett. 2013, 15, 429.
[20]	Chen, J. Q.; Dong, Z. B. Synthesis 2020, 52, 3714.
[21]	Wang, D.; Du, J.; Lin, W. L.; Li, Y. S.; Dong, Z. B. J. Org. Chem. 2023, 88, 16906.
[22]	Ma, J.; Wang, X.; Hao, E. J.; Shi, Z.; Dong, Z. B. J. Org. Chem. 2022, 87, 5568.
[23]	Liu, X.; Liu, M.; Xu, W.; Zeng, M. T.; Zhu, H.; Chang, C. Z.; Dong, Z. B. Green Chem. 2017, 19, 5591.
[24]	Dai, Y. B.; Wang, F.; Zhu, S. Q.; Chu, L. L. Chin. Chem. Lett. 2022, 33, 4074.
[25]	Wang, Y. F.; Ping, Y. Y.; Kong, W. Q. Chin. Chem. Lett. 2023, 34, 108453.
[26]	Li, S. L.; Chen, Q. Y.; Zhang, Z. M.; Zhang, J. L. Green Synth. Catal. 2021, 2, 374.
[27]	Min, J. H.; Zheng, Z. j.; Huang, S. S.; He, R. R.; Xu, Z.; Bouillon, J. P.; Xu, L. W. Green Synth. Catal. 2021, 2, 350.
[28]	Zhang, D. H.; Liu, Z. J.; Yum, E. K.; Larock, R. C. J. Org. Chem. 2007, 72, 251.
[29]	Zhou, F.; Han, X. L.; Lu, X. Y. J. Org. Chem. 2011, 76, 1491.
[30]	Ma, B.; Wu, Z.; Huang, B.; Liu, L.; Zhang, J. L. Chem. Commun. 2016, 52, 9351.
[31]	Liu, X. W.; Li, S. S.; Dai, D. T.; Zhao, M.; Shan, C. C.; Xu, Y. H.; Loh, T. P. Org. Lett. 2019, 21, 3696.
[32]	Zhao, X. M.; Zhou, J. B.; Lin, S. Y.; Jin, X. K.; Liu, R. H. Org. Lett. 2017, 19, 976.
[33]	Yoon, H.; Rölz, M.; Landau, F.; Lautens, M. Angew. Chem., Int. Ed. 2017, 56, 10920.
[34]	Yao, T. L.; He, D. Org. Lett. 2017, 19, 842.
[35]	Yuan, K.; Liu, L. N.; Chen, J. Y.; Guo, S. J.; Yao, H. Q.; Lin, A. J. Org. Lett. 2018, 20, 3477. doi: 10.1021/acs.orglett.8b01235 pmid: 29863361
[36]	Lei, L.; Zou, P. S.; Wang, Z. X.; Liang, C.; Hou, C.; Mo, D. L. Org. Lett. 2022, 24, 663. doi: 10.1021/acs.orglett.1c04120 pmid: 34995468
[37]	Schempp, T. T.; Daniels, B. E.; Staben, S. T.; Stivala, C. E. Org. Lett. 2017, 19, 3616.
[38]	Pérez-Gómez, M.; Hernández-Ponte, S.; Bautista, D.; García-López, J. A. Chem. Commun. 2017, 53, 2842.
[39]	Liu, R. R.; Wang, Y. G.; Li, Y. L.; Huang, B. B.; Liang, R. X.; Jia, Y. X. Angew. Chem., Int. Ed. 2017, 56, 7475.
[40]	Li, J. X.; Yang, S. R.; Wu, W. Q.; Qi, C. R.; Deng, Z. X.; Jiang, H. F. Tetrahedron 2014, 70, 1516.
[41]	Hu, P. F.; Snyder, S. A. J. Am. Chem. Soc. 2017, 139, 5007.
[42]	Gao, Y.; Gao, Y. L.; Wu, W. Q.; Jiang, H. F.; Yang, X. B.; Liu, W. B.; Li, C. J. Chem. Eur. J. 2017, 23, 793.
[43]	Yao, T. L.; Liu, T.; Zhang, C. H. Chem. Commun. 2017, 53, 2386.
[44]	Wu, Y.; Xu, B.; Zhao, G. F.; Pan, Z. J.; Zhang, Z. M.; Zhang, J. L. Chin. J. Chem. 2021, 39, 3255.
[45]	Whyte, A.; Bajohr, J.; Arora, R.; Torelli, A.; Lautens, M. Angew. Chem., Int. Ed. 2021, 60, 20231.
[46]	Ramesh, K.; Satyanarayana, G. Eur. J. Org. Chem. 2019, 2019, 8356.
[47]	Wang, M. M.; Lu, S. M.; Li, C. ACS Catal. 2022, 12, 10801.
[48]	Gao, Y.; Xiong, W. F.; Chen, H. J.; Wu, W. Q.; Peng, J. W.; Gao, Y. L.; Jiang, H. F. J. Org. Chem. 2015, 80, 7456.
[49]	Ishikura, M.; Takahashi, N.; Yamada, K.; Yanada, R. Tetrahedron 2006, 62, 11580.

Entry	Catalyst	Solvent	Base	Temp./℃	Yield/%
1	Pd(PPh₃)₄	THF	K₂CO₃	80	49
2	Pd(PPh₃)₄	Toluene	K₂CO₃	80	N.R.
3	Pd(PPh₃)₄	1,4-Dioxane	K₂CO₃	80	N.R.
4	Pd(PPh₃)₄	MTBE	K₂CO₃	80	Trace
5	Pd(PPh₃)₄	EtOAc	K₂CO₃	80	Trace
6	Pd(PPh₃)₄	DMSO	K₂CO₃	80	Trace
7	Pd(PPh₃)₄	DME	K₂CO₃	80	Trace
8	Pd(PPh₃)₄	DMF	K₂CO₃	80	76
9	Pd(PPh₃)₄	DMA	K₂CO₃	80	91
10	Pd(PPh₃)₄	DMA	K₃PO₄	80	64
11	Pd(PPh₃)₄	DMA	Cs₂CO₃	80	69
12	Pd(PPh₃)₄	DMA	Na₂CO₃	80	67
13	Pd(PPh₃)₄	DMA	t-BuONa	80	N.R.
14	Pd(dba)₂	DMA	K₂CO₃	80	61
15	Pd(PPh₃)₂Cl₂	DMA	K₂CO₃	80	77
16	PdBr₂	DMA	K₂CO₃	80	90
17	Pd(OAc)₂	DMA	K₂CO₃	80	91
18^b	Pd(OAc)₂	DMA	K₂CO₃	80	80
19	Pd(PPh₃)₄	DMA	K₂CO₃	100	87
20	Pd(PPh₃)₄	DMF	K₂CO₃	100	96

Entry	Catalyst	Solvent	Base	Temp./℃	Yield/%
1	Pd(PPh₃)₄	THF	K₂CO₃	80	49
2	Pd(PPh₃)₄	Toluene	K₂CO₃	80	N.R.
3	Pd(PPh₃)₄	1,4-Dioxane	K₂CO₃	80	N.R.
4	Pd(PPh₃)₄	MTBE	K₂CO₃	80	Trace
5	Pd(PPh₃)₄	EtOAc	K₂CO₃	80	Trace
6	Pd(PPh₃)₄	DMSO	K₂CO₃	80	Trace
7	Pd(PPh₃)₄	DME	K₂CO₃	80	Trace
8	Pd(PPh₃)₄	DMF	K₂CO₃	80	76
9	Pd(PPh₃)₄	DMA	K₂CO₃	80	91
10	Pd(PPh₃)₄	DMA	K₃PO₄	80	64
11	Pd(PPh₃)₄	DMA	Cs₂CO₃	80	69
12	Pd(PPh₃)₄	DMA	Na₂CO₃	80	67
13	Pd(PPh₃)₄	DMA	t-BuONa	80	N.R.
14	Pd(dba)₂	DMA	K₂CO₃	80	61
15	Pd(PPh₃)₂Cl₂	DMA	K₂CO₃	80	77
16	PdBr₂	DMA	K₂CO₃	80	90
17	Pd(OAc)₂	DMA	K₂CO₃	80	91
18^b	Pd(OAc)₂	DMA	K₂CO₃	80	80
19	Pd(PPh₃)₄	DMA	K₂CO₃	100	87
20	Pd(PPh₃)₄	DMF	K₂CO₃	100	96