Pd-Catalyzed Synthesis of Polysubstituted Pyrroles from Anilines, Alkyne Esters and Alkynes

doi:10.6023/cjoc202504023

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (12): 4481-4489.DOI: 10.6023/cjoc202504023 Previous Articles Next Articles

ARTICLES

钯催化苯胺、炔酯和炔烃合成多取代吡咯

周艳^a, 王梦迪^a, 胡旭华^b, 郭文^a, 姚子健^a, 刘传祥^a^,^*(), 郭勋祥^b^,^*()

^a 上海应用技术大学化学与环境工程学院上海 201418
^b 上海交通大学系统生物医学研究院系统生物医学教育部重点实验室系统生物医学教育部重点实验室上海 200240

收稿日期:2025-04-20 修回日期:2025-05-20 发布日期:2025-06-06
通讯作者: 刘传祥, 郭勋祥
基金资助:
国家自然科学基金(22271193); 上海市教委、上海市教育发展基金会“曙光计划”(23SG51); 上海交通大学医工交叉基金(YG2021QN52)

Pd-Catalyzed Synthesis of Polysubstituted Pyrroles from Anilines, Alkyne Esters and Alkynes

Yan Zhou^a, Mengdi Wang^a, Xuhua Hu^b, Wen Guo^a, Zijian Yao^a, Chuanxiang Liu^a^,^*(), Xunxiang Guo^b^,^*()

^a School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418
^b Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240

Received:2025-04-20 Revised:2025-05-20 Published:2025-06-06
Contact: Chuanxiang Liu, Xunxiang Guo
Supported by:
National Natural Science Foundation of China(22271193); Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(23SG51); Interdisciplinary Program of Shanghai Jiao Tong University(YG2021QN52)

1. .pdf(3442KB)

Abstract

A palladium-catalyzed three-component annulation of anilines, alkyne esters, and alkynes has been developed for the synthesis of polysubstituted pyrroles. The protocol demonstrates broad substrate scope and good functional group compatibility. The application experiments including gram-scale synthesis and derivatization of the product are performed to illustrate the synthetic potential. This method offers mild conditions and efficient access to polysubstituted pyrroles.

Key words: Pd-catalysis, polysubstituted pyrrole, annulation, aniline, alkyne

Cite this article

Yan Zhou, Mengdi Wang, Xuhua Hu, Wen Guo, Zijian Yao, Chuanxiang Liu, Xunxiang Guo. Pd-Catalyzed Synthesis of Polysubstituted Pyrroles from Anilines, Alkyne Esters and Alkynes[J]. Chinese Journal of Organic Chemistry, 2025, 45(12): 4481-4489.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 7

References 15

[1]	(a) Gupta S. S.; Parmar D.; Kumar R.; Chandra D.; Sharma U. Catal. Rev. 2024, 66, 713. doi: 10.1080/01614940.2022.2097640
	(b) Blaszczyk S. A.; Glazier D. A.; Tang W. Acc. Chem. Res. 2020, 53, 231. doi: 10.1021/acs.accounts.9b00477
[2]	Stuart D. R.; Bertrand-Laperle M.; Burgess K. M. N.; Fagnou K. J. Am. Chem. Soc. 2008, 130, 16474. doi: 10.1021/ja806955s pmid: 19554684
[3]	Shi Z.; Zhang C.; Li S.; Pan D.; Ding S.; Cui Y.; Jiao N. Angew. Chem., Int. Ed. 2009, 48, 4572. doi: 10.1002/anie.v48:25
[4]	(a) Stuart D. R.; Alsabeh P.; Kuhn M.; Fagnou K. J. Am. Chem. Soc. 2010, 132, 18326. doi: 10.1021/ja1082624 pmid: 21133376
	(b) Chen J.; Song G.; Pan C.-L.; Li X. Org. Lett. 2010, 12, 5426. doi: 10.1021/ol1022596 pmid: 21133376
	(c) Zhang G.; Yu H.; Qin G.; Huang H. Chem. Commun. 2014, 50, 4331. doi: 10.1039/C3CC49751H pmid: 21133376
[5]	(a) Kondoh A.; Yorimitsu H.; Oshima K. Org. Lett. 2010, 12, 1476. doi: 10.1021/ol1001544 pmid: 23125101
	(b) Yao B.; Wang Q.; Zhu J. Angew. Chem., Int. Ed. 2012, 51, 12311. doi: 10.1002/anie.201205596 pmid: 23125101
[6]	(a) Sagadevan A.; Ragupathi A.; Hwang K. C. Angew. Chem., Int. Ed. 2015, 54, 13896. doi: 10.1002/anie.v54.47
	(b) Hou Z.-W.; Mao Z.-Y.; Zhao H.-B.; Melcamu Y. Y.; Lu X.; Song J.; Xu H.-C. Angew. Chem., Int. Ed. 2016, 55, 9168. doi: 10.1002/anie.v55.32
	(c) Jagtap P. A.; Lokolkar M. S.; Bhanage B. M. J. Org. Chem. 2023, 88, 10960. doi: 10.1021/acs.joc.3c00954
[7]	(a) Wilkerson W. W.; Copeland R. A.; Covington M.; Trzaskos J. M. J. Med. Chem. 1995, 38, 3895. pmid: 11714612
	(b) Lee H.; Lee J.; Lee S.; Shin Y.; Jung W.; Kim J.-H.; Park K.; Kim K.; Cho H. S.; Ro S.; Lee S.; Jeong S. W.; Choi T.; Chung H.-H.; Koh J. S. Bioorg. Med. Chem. Lett. 2001, 11, 3069. pmid: 11714612
	(c) Aiello A.; D’Esposito M.; Fattorusso E.; Menna M.; Müller W. E. G.; Perović-Ottstadt S.; Schröder H. C. Bioorg. Med. Chem. 2006, 14, 17. pmid: 11714612
	(d) La Regina G.; Silvestri R.; Artico M.; Lavecchia A.; Novellino E.; Befani O.; Turini P.; Agostinelli E. J. Med. Chem. 2007, 50, 922. doi: 10.1021/jm060882y pmid: 11714612
	(e) Wood J. M.; Furkert D. P.; Brimble M. A. Nat. Prod. Rep. 2019, 36, 289. doi: 10.1039/C8NP00051D pmid: 11714612
[8]	(a) Estévez V.; Villacampa M.; Menéndez J. C. Chem. Soc. Rev. 2014, 43, 4633. doi: 10.1039/C3CS60015G
	(b) Guo X.-X.; Gu D.-W.; Wu Z.; Zhang W. Chem. Rev. 2015, 115, 1622. doi: 10.1021/cr500410y
	(c) Hong F.-L.; Ye L.-W. Acc. Chem. Res. 2020, 53, 2003. doi: 10.1021/acs.accounts.0c00417
	(d) Duc D. X. Curr. Org. Chem. 2020, 24, 622. doi: 10.2174/1385272824666200228121627
	(e) Xu X.; Chen J.; Ke J.; Zhang K.; Wu P.; Wang S. Chin. J. Org. Chem. 2021, 41, 206. (in Chinese) doi: 10.6023/cjoc202005018
	(徐学涛, 陈洁, 柯俊杰, 张焜, 吴盼盼, 王少华, 有机化学, 2021, 41, 206.) doi: 10.6023/cjoc202005018
[9]	Liu W.; Jiang H.; Huang L. Org. Lett. 2010, 12, 312. doi: 10.1021/ol9026478
[10]	Chen X.; Li X.; Wang N.; Jin J.; Lu P.; Wang Y. Eur. J. Org. Chem. 2012, 4380.
[11]	Zhang L.; Wang X.; Li S.; Wu J. Tetrahedron 2013, 69, 3805. doi: 10.1016/j.tet.2013.03.061
[12]	(a) Hu Z.-Y.; Zhang Y.; Li X.-C.; Zi J.; Guo X.-X. Org. Lett. 2019, 21, 989. doi: 10.1021/acs.orglett.8b03976
	(b) Yang H.-R.; Hu Z.-Y.; Li X.-C.; Wu L.; Guo X.-X. Org. Lett. 2022, 24, 8392. doi: 10.1021/acs.orglett.2c03465
	(c) Zhao R.; Wu L.; Chen S.-W.; Cui Z.; Hu X.-H.; Yang H.-R.; Ye H.; Miao C.-B.; Guo X.-X. Eur. J. Org. Chem. 2024, 27, e202300919. doi: 10.1002/ejoc.v27.3
	(d) Chen S.-W.; Hu X.-H.; Wu L.; Miao C.-B.; Guo X.-X. Tetrahedron Lett. 2025, 159, 155506. doi: 10.1016/j.tetlet.2025.155506
[13]	(a) Anderson W. K.; Halat M. J.; Rick A. C. J. Med. Chem. 1980, 23, 87. pmid: 3783586
	(b) Anderson W. K.; Milowsky A. S. J. Med. Chem. 1986, 29, 2241. pmid: 3783586
[14]	Rafaniello A. A.; Rizzacasa M. A. Org. Lett. 2020, 22, 1972. doi: 10.1021/acs.orglett.0c00319 pmid: 32065753
[15]	Zhao D.; Zhu Y.; Guo S.; Chen W.; Zhang G.; Yu Y. Tetrahedron 2017, 73, 2872. doi: 10.1016/j.tet.2017.03.074

Entry	Catalyst	Solvent	Oxidant	Additive	Yield^b/%
1	Pd(OAc)₂	MeCN	K₂S₂O₈	HOAc	43
2	Pd(PPh₃)₄	MeCN	K₂S₂O₈	HOAc	39
3	[PdCl(C₃H₅)]₂	MeCN	K₂S₂O₈	HOAc	16
4	Pd(dba)₂	MeCN	K₂S₂O₈	HOAc	37
5	Pd(TFA)₂	MeCN	K₂S₂O₈	HOAc	51
6	Pd(TFA)₂	THF	K₂S₂O₈	HOAc	23
7	Pd(TFA)₂	1,4-Dioxane	K₂S₂O₈	HOAc	32
8	Pd(TFA)₂	DMF	K₂S₂O₈	HOAc	Trace
9	Pd(TFA)₂	DMSO	K₂S₂O₈	HOAc	Trace
10	Pd(TFA)₂	DMAc	K₂S₂O₈	HOAc	Trace
11	Pd(TFA)₂	CHCl₃	K₂S₂O₈	HOAc	23
12	Pd(TFA)₂	Toluene	K₂S₂O₈	HOAc	22
13	Pd(TFA)₂	MeCN	Na₂S₂O₈	HOAc	10
14	Pd(TFA)₂	MeCN	O₂	HOAc	37
15	Pd(TFA)₂	MeCN	TBHP	HOAc	35
16	Pd(TFA)₂	MeCN	PhI(OAc)₂	HOAc	Trace
17	Pd(TFA)₂	MeCN	BQ	HOAc	Trace
18	Pd(TFA)₂	MeCN	K₂S₂O₈	TFA	Trace
19	Pd(TFA)₂	MeCN	K₂S₂O₈	PivOH	45
20	Pd(TFA)₂	MeCN	K₂S₂O₈	—	12
21^c	Pd(TFA)₂	MeCN	K₂S₂O₈	HOAc	46
22^d	Pd(TFA)₂	MeCN	K₂S₂O₈	HOAc	41
23^e	Pd(TFA)₂	MeCN	K₂S₂O₈	HOAc	39
24^f	Pd(TFA)₂	MeCN	K₂S₂O₈	HOAc	52
25^g	Pd(TFA)₂	MeCN	K₂S₂O₈	HOAc	55
26^h	Pd(TFA)₂	MeCN	K₂S₂O₈	HOAc	61

Entry	Catalyst	Solvent	Oxidant	Additive	Yield^b/%
1	Pd(OAc)₂	MeCN	K₂S₂O₈	HOAc	43
2	Pd(PPh₃)₄	MeCN	K₂S₂O₈	HOAc	39
3	[PdCl(C₃H₅)]₂	MeCN	K₂S₂O₈	HOAc	16
4	Pd(dba)₂	MeCN	K₂S₂O₈	HOAc	37
5	Pd(TFA)₂	MeCN	K₂S₂O₈	HOAc	51
6	Pd(TFA)₂	THF	K₂S₂O₈	HOAc	23
7	Pd(TFA)₂	1,4-Dioxane	K₂S₂O₈	HOAc	32
8	Pd(TFA)₂	DMF	K₂S₂O₈	HOAc	Trace
9	Pd(TFA)₂	DMSO	K₂S₂O₈	HOAc	Trace
10	Pd(TFA)₂	DMAc	K₂S₂O₈	HOAc	Trace
11	Pd(TFA)₂	CHCl₃	K₂S₂O₈	HOAc	23
12	Pd(TFA)₂	Toluene	K₂S₂O₈	HOAc	22
13	Pd(TFA)₂	MeCN	Na₂S₂O₈	HOAc	10
14	Pd(TFA)₂	MeCN	O₂	HOAc	37
15	Pd(TFA)₂	MeCN	TBHP	HOAc	35
16	Pd(TFA)₂	MeCN	PhI(OAc)₂	HOAc	Trace
17	Pd(TFA)₂	MeCN	BQ	HOAc	Trace
18	Pd(TFA)₂	MeCN	K₂S₂O₈	TFA	Trace
19	Pd(TFA)₂	MeCN	K₂S₂O₈	PivOH	45
20	Pd(TFA)₂	MeCN	K₂S₂O₈	—	12
21^c	Pd(TFA)₂	MeCN	K₂S₂O₈	HOAc	46
22^d	Pd(TFA)₂	MeCN	K₂S₂O₈	HOAc	41
23^e	Pd(TFA)₂	MeCN	K₂S₂O₈	HOAc	39
24^f	Pd(TFA)₂	MeCN	K₂S₂O₈	HOAc	52
25^g	Pd(TFA)₂	MeCN	K₂S₂O₈	HOAc	55
26^h	Pd(TFA)₂	MeCN	K₂S₂O₈	HOAc	61

钯催化苯胺、炔酯和炔烃合成多取代吡咯

Pd-Catalyzed Synthesis of Polysubstituted Pyrroles from Anilines, Alkyne Esters and Alkynes

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 7

References 15

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Yanan Cai, Xiangtai Meng. 4-Dimethylamino-pyridine (DMAP)-Promoted [5＋1] Annulation of Isoquinolinium Zwitterions with α-Bromophenones: An Efficient Approach to Hydrogenated 1,4-Thiazino[2,3-a]isoquinoline Tricyclic Derivatives [J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3429-3440.
[2]	Sen Zhang, Lingyun Jiang, Yu Xin, Nianyu Huang, Nengzhong Wang. Organic Base-Promoted [2+3] Annulation of Arylglyoxal Monohydrates with Allyl Phosphonium Salts: Efficient Syntheses of Cyclopentenones [J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3420-3428.
[3]	Yinsheng Miao, Lei Zhang, Jianqi Chen, Lili Wang, Zheng Duan. Synthesis of Pyrazolo(iso)quinoline Derivatives from Aryl Alkynes and N-Imine(iso)quinoline Ylides Catalyzed by Bisphosphonium Salt [J]. Chinese Journal of Organic Chemistry, 2025, 45(8): 2876-2884.
[4]	Ling Zhao, Xiaohui Zhu, Hua Chen, Xueli Zheng, Weichao Xue, Jiaqi Xu, Haiyan Fu, Ruixiang Li. Synthesis of Quinazoline through Ruthenium-Catalyzed Hydrogen Transfer/Annulation Reaction between 2-Nitrobenzyl Alcohol and Benzylamine [J]. Chinese Journal of Organic Chemistry, 2025, 45(8): 2836-2847.
[5]	Xiaopei Chen, Qinglong Wang, Xuehui Hou, Chuanchuan Wang, Zhiwei Ma, Jingyu Zhang. Recent Progress on the Application of CF₃-Imidoyl Sulfoxonium Ylides in Annulation Reactions [J]. Chinese Journal of Organic Chemistry, 2025, 45(8): 2796-2814.
[6]	Zhen Liang, Weiyan Xu, Yi Chen, Huayu Qiu, Yezhe Zhao, Jiabin Shen, Min Wang. Iridium-Catalyzed Synthesis of Indole Derivatives from N-Aryl-2-aminopyridines and Vinylene Carbonate [J]. Chinese Journal of Organic Chemistry, 2025, 45(6): 2149-2156.
[7]	Gang Chen, Dong Chen, Guangjie Nie, Linxuan Li, Hui Yao, Nengzhong Wang, Nianyu Huang. Phosphine-Catalyzed [2＋3] Annulation of Aurone-Derived Azadienes with Amino Crotonates [J]. Chinese Journal of Organic Chemistry, 2025, 45(6): 2139-2148.
[8]	Yanmei Yan, Hongli Zhang, Min Yuan, Ruijia Qin, Zhenxing Ren, Yingchun He. One-Pot Metal-Free Synthesis of New 1,2,3-Triazolobenzodiaze-pinones by a Sequential Ugi 4CR/Alkyne-Azide Cycloaddition Reaction [J]. Chinese Journal of Organic Chemistry, 2025, 45(10): 3923-3931.
[9]	Xu Zhang, Peisen Zou, Xiaoqing Liu, Hongyan Bi, Dongliang Mo. Recent Progress in Gold-Catalyzed Intramolecular Cyclization of Alkynes and Its Applications [J]. Chinese Journal of Organic Chemistry, 2025, 45(10): 3755-3776.
[10]	Fan Yang, Xiaomeng Fan, Xuejing Yao, Ruijie Mi, Songjie Yu, Xingwei Li, Jian Xiao. Rhodium(III)-Catalyzed Annulative Coupling between Sulfoxonium Ylides and Diazo Compounds [J]. Chinese Journal of Organic Chemistry, 2025, 45(1): 331-342.
[11]	Yushen Gao, Yuanyuan Gao, An'an Zhang, Lu Li, Weizhi Geng, Fenghua Zhang, Fei Li, Lantao Liu. BF₃•OEt₂ Mediated Intramolecular Cyclization of 2-Alkynylanilines Approach to 3-Sulfenylindoles [J]. Chinese Journal of Organic Chemistry, 2024, 44(9): 2785-2795.
[12]	Huan Jin, Yanjun Zhu, Fang Li, Yunfei Luo. Synthesis of New Rh-Cp Complex with an Ester Group Tethered on the Cp Ring and Its Application in the Catalytic Synthesis of iso-Quinolines [J]. Chinese Journal of Organic Chemistry, 2024, 44(9): 2906-2914.
[13]	Leiyang Lv, Yani Luo, Zhiping Li. Advances in the Synthesis of Organogermaniums Based on the Addition Reactions of Alkenes and Alkynes [J]. Chinese Journal of Organic Chemistry, 2024, 44(7): 2092-2109.
[14]	Tong Xu, Ning Zhang, Yonghong Zhang, Bin Wang, Yu Xia, Weiwei Jin, Pinru Jin, Chenjiang Liu. Copper-Based Solid Wastes Promoted Cross-Coupling Reactions of Terminal Alkynes [J]. Chinese Journal of Organic Chemistry, 2024, 44(7): 2341-2349.
[15]	Jiasheng Wang, Zeshu Wang, Weimin He, Longwu Ye. Research Progress on the Hydroamination of o-Alkynylanilines for the Synthesis of Axially Chiral Indoles [J]. Chinese Journal of Organic Chemistry, 2024, 44(6): 1786-1792.