吲哚-环丙烷的分子内开环反应※

doi:10.6023/A22010002

化学学报 ›› 2022, Vol. 80 ›› Issue (3): 255-258.DOI: 10.6023/A22010002 上一篇下一篇

所属专题：中国科学院青年创新促进会合辑

研究通讯

吲哚-环丙烷的分子内开环反应^※

郑龙^a, 王丽佳^a^,^b^,^c^,^*(), 唐勇^a^,^*()

a 中国科学院上海有机化学研究所中国科学院大学金属有机化学国家重点实验室上海 200032
b 华东师范大学化学与分子工程学院上海分子治疗与新药创制工程中心上海 200062
c 华东师范大学化学与分子工程学院上海分子智造前沿科学中心上海 200062

投稿日期:2022-01-01 发布日期:2022-02-11
通讯作者: 王丽佳, 唐勇
作者简介:
^※ 庆祝中国科学院青年创新促进会十年华诞.
基金资助:
国家自然科学基金(91956103); 国家自然科学基金(21772224)

Intramolecular Ring-opening of Indole-cyclopropanes^※

Long Zheng^a, Lijia Wang^a^,^b^,^c(), Yong Tang^a()

a State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, CAS, University of Chinese Academy of Sciences, Shanghai 200032, China
b Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China
c Shanghai Frontiers Science Center of Molecule Intelligent Syntheses, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China

Received:2022-01-01 Published:2022-02-11
Contact: Lijia Wang, Yong Tang
About author:
^※ Dedicated to the 10th anniversary of the Youth Innovation Promotion Association, CAS.
Supported by:
National Natural Science Foundation of China(91956103); National Natural Science Foundation of China(21772224)

文章分享

1. Supporting Information-A22010002.pdf(2620KB)

摘要/Abstract

本工作使用In(NTf₂)₃作为金属Lewis酸催化剂, 实现了吲哚-环丙烷分子内的亲核开环反应, 克服了脂肪族取代的环丙烷活性低、不易实现开环反应的难题. 利用该方法可以简单高效地构建吡咯并[1,2-a]-吲哚骨架结构的化合物. 该反应条件温和, 底物普适性广, 最终以15个反应实例, 高达96%收率得到一系列吡咯并[1,2-a]-吲哚化合物.

关键词: In(NTf₂)₃, 环丙烷, 亲核开环, 分子内反应, 吡咯并[1, 吡咯并[1,2-a]-吲哚

Donor-acceptor cyclopropanes as efficient three-carbon synthetic building blocks were widely employed in the synthesis of many natural products and complex drug molecules. However, the ring-opening of aliphatic substituted cyclopropanes, owing to their poor reactivity, usually suffers from the harsh reaction conditions such as strong Lewis acid, large amount of catalyst, high reaction temperature and so on. In this paper, In(NTf₂)₃ was found as a powerful Lewis acid to catalyze the intramolecular nucleophilic ring-opening reaction of donor-acceptor cyclopropane with indole. This reaction could be used to construct the pyrrolo[1,2-a]-indole framework structure in a facile way. This method could be conducted in mild reaction conditions with a broad substrate scope (15 examples), leading to the target products in up to 96% yield. The general procedure is as following: To a dry Schlenk tube in a glove box, was placed In(NTf₂)₃ (0.1 equiv.), 4 Å molecular sieve (50 mg) and a stir bar. The tube was capped and brought out of the glovebox. After connected to argon via a typical Schlenk line system, a solution of 1 (1.0 equiv.) in PhCl (1 mL) was added dropwise until the reaction was completed (monitored by thin-layer chromatography). Et₃N was added to quench the reaction and the reaction mixture was filtered through a thin layer of silica gel and eluted with EtOAc (100 mL). After removal of the volatiles under reduced pressure, the residue was purified by flash chromatography over silica gel to afford the product. When indole substrate contains electron-withdrawing substituents, the reaction temperature needs to be increased to 100 ℃ to obtain the target product.

Key words: In(NTf₂)₃, cyclopropane, nucleophilic ring-opening, intramolecular reaction, pyrrolo[1, pyrrolo[1,2-a]-indole

引用此文

郑龙, 王丽佳, 唐勇. 吲哚-环丙烷的分子内开环反应^※[J]. 化学学报, 2022, 80(3): 255-258.

Long Zheng, Lijia Wang, Yong Tang. Intramolecular Ring-opening of Indole-cyclopropanes^※[J]. Acta Chimica Sinica, 2022, 80(3): 255-258.

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

分享此文

图/表 4

图1. 含有吡咯并[1,2-a]-吲哚骨架结构的天然产物

Figure 1. Natural products containing pyrrolo[1,2-a]-indole backbone

图2. 吲哚的亲核进攻反应

Figure 2. The nucleophilic attack of indole

Entry	Lewis acid	Solvent	Time/h	Conv./%	Yield^b/%
1	Cu(OTf)₂	DCM	24	0	—
2	Zn(OTf)₂	DCM	24	0	—
3	Fe(OTf)₃	DCM	24	0	—
4	La(OTf)₃	DCM	24	0	—
5	YbOTf)₃	DCM	24	0	—
6	Ga(OTf)₃	DCM	24	15	15
7	Sc(OTf)₃	DCM	24	29	11
8	In(OTf)₃	DCM	24	76	66
9	InCl₃	DCM	24	8	7
10	InBr₃	DCM	24	38	34
11	In(NTf₂)₃	DCM	24	86	82(80)^c
12	In(NTf₂)₃	THF	72	—	—
13	In(NTf₂)₃	Toluene	11	100	99(90) ^c
14	In(NTf₂)₃	PhCl	7	100	99(90)^c

表1. 反应条件优化a

Table 1. Optimization of reaction conditionsa

图3. 底物拓展a

Figure 3. Substrate scopea a Reaction conditions: 1a (0.10 mmol), In(NTf2)3 (10 mol%), PhCl (1 mL), with 50 mg 4 Å MS at room temperature, isolated yields. b Reacting at 100 ℃.

参考文献 14

[1]	(a) Magnus, P.; Gallagher, T.; Brown, P.; Huffman, J. C. J. Am. Chem. Soc. 1984, 106, 2105. doi: 10.1021/ja00319a034
	(b) Gataullin, R. R. Russ. J. Org. Chem. 2009, 45, 321. doi: 10.1134/S1070428009030014
	(c) Dethe, D. H.; Erande, R. D.; Ranjan, A. J. Am. Chem. Soc. 2011, 133, 2864. doi: 10.1021/ja1116974
	(d) Vallakati, R.; May, J. A. J. Am. Chem. Soc. 2012, 134, 6936. doi: 10.1021/ja301387k
	(e) Zeldin, R. M.; Toste, F. D. Chem. Sci. 2011, 2, 1706. doi: 10.1039/c1sc00290b
	(f) Cheng, S.; Seo, J.; Huang, B. T.; Napolitano, T. Int. J. Oncol. 2016, 49, 1815. doi: 10.3892/ijo.2016.3703
	(g) Ghosh, A.; Bainbridge, D. T.; Stanley, L. M. J. Org. Chem. 2016, 81, 7945. doi: 10.1021/acs.joc.6b01730
	(h) Zhan, L.; Hu, W.; Wang, M.; Huang, B.; Long, Y.-Q. Acta Chim. Sinica 2021, 79, 903. (in Chinese) doi: 10.6023/A21060252
	(占林俊, 胡玮, 王梅, 黄斌, 龙亚秋, 化学学报, 2021, 79, 903). doi: 10.6023/A21060252
	(i) Zhou, B.; Liang, R.; Cao, Z.; Zhou, P.; Jia, Y. Acta Chim. Sinica 2021, 79, 176. (in Chinese) doi: 10.6023/A20110520
	(周波, 梁仁校, 曹中艳, 周平海, 贾义霞, 化学学报, 2021, 79, 176). doi: 10.6023/A20110520
[2]	Hong, L.; Sun, W. S.; Liu, C. X.; Wang, L.; Wang, R. Chem. Eur. J. 2010, 16, 440. doi: 10.1002/chem.v16:2
[3]	Patil, D. V.; Cavitt, M. A.; France, S. Org. Lett. 2011, 13, 5820. doi: 10.1021/ol202431x
[4]	Tejeda, J. E. C.; Landschoot, B. K.; Kerr, M. A. Org. Lett. 2016, 18, 2142. doi: 10.1021/acs.orglett.6b00768
[5]	(a) Yip, K. T.; Yang, D. Org. Lett. 2011, 13, 2134. doi: 10.1021/ol2006083
	(b) Zhang, W.; Chen, P. H.; Liu, G. S. Angew. Chem. Int. Ed. 2017, 56, 5336. doi: 10.1002/anie.201700889
[6]	For reviews and recent examples, see: (a) Wong, H. N. C.; Hon, M. Y.; Tse, C. W.; Yip, Y. C.; Tanko, J.; Hudlicky, T. Chem. Rev. 1989, 89, 165. doi: 10.1021/cr00091a005
	(b) Reissig, H. U.; Zimmer, R. Chem. Rev. 2003, 103, 1151. doi: 10.1021/cr010016n
	(c) Carson, C. A.; Kerr, M. A. Chem. Soc. Rev. 2009, 38, 3051. doi: 10.1039/b901245c
	(d) Tang, P.; Qin, Y. Synthesis 2012, 44, 2969. doi: 10.1055/s-00000084
	(e) Wang, Z. W. Synlett 2012, 23, 2311. doi: 10.1055/s-00000083
	(f) Reissig, H. U.; Zimmer, R. Angew. Chem. Int. Ed. 2015, 54, 5009. doi: 10.1002/anie.v54.17
	(g) Wang, Y.; Yu, Z.-X. Acc. Chem. Res. 2015, 48, 2288. doi: 10.1021/acs.accounts.5b00037
	(h) Qiu, Y.; Lu, K.; Wei, B.; Qian, Z.; He, Z. Chin. J. Org. Chem. 2021, 41, 4066. (in Chinese) doi: 10.6023/cjoc202104036
	(仇裕鹤, 鲁康辉, 韦邦尺, 潜振凯, 贺峥杰, 有机化学, 2021, 41, 4066.)
[7]	For reviews, see: (a) Yu, M.; Pagenkopf, B. L. Tetrahedron 2005, 61, 321. doi: 10.1016/j.tet.2004.10.077 pmid: 25425071
	(b) Rubin, M.; Rubina, M.; Gevorgyan, V. Chem. Rev. 2007, 107, 3117. doi: 10.1021/cr050988l pmid: 25425071
	(c) Cavitt, M. A.; Phun, L. H.; France, S. Chem. Soc. Rev. 2014, 43, 804. doi: 10.1039/C3CS60238A pmid: 25425071
	(d) de Nanteuil, F.; De Simone, F.; Frei, R.; Benfatti, F.; Serrano, E.; Waser, J. Chem. Commun. 2014, 50, 10912. doi: 10.1039/C4CC03194F pmid: 25425071
	(e) Schneider, T. F.; Kaschel, J.; Werz, D. B. Angew. Chem., Int. Ed. 2014, 53, 5504. doi: 10.1002/anie.v53.22 pmid: 25425071
	(f) Grover, H. K.; Emmett, M. R.; Kerr, M. A. Org. Biomol. Chem. 2015, 13, 655. doi: 10.1039/c4ob02117g pmid: 25425071
[8]	(a) Beal, R. B.; Dombroski, M. A.; Snider, B. B. J. Org. Chem. 1986, 51, 4391. doi: 10.1021/jo00373a010
	(b) Tanimori, S.; Niki, T.; He, M. Q.; Nakayama, M. Heterocycles 1994, 38, 1533. doi: 10.3987/COM-94-6714
	(c) Kotsuki, H.; Arimura, K.; Maruzawa, R.; Ohshima, R. Synlett 1999, 5, 650.
[9]	(a) Xing, S. Y.; Pan, W. Y.; Liu, C.; Ren, J.; Wang, Z. W. Angew. Chem., Int. Ed. 2010, 49, 3215. doi: 10.1002/anie.v49:18
	(b) Zhu, W. J.; Fang, J.; Liu, Y.; Ren, J.; Wang, Z. W. Angew. Chem. Int. Ed. 2013, 52, 2032. doi: 10.1002/anie.v52.7
[10]	For reviews, see: (a) Liao, S.; Sun, X. L.; Tang, Y. Acc. Chem. Res. 2014, 47, 2260. doi: 10.1021/ar800104y
	(b) Wang, L.; Tang, Y. Isr. J. Chem. 2016, 56, 463. doi: 10.1002/ijch.201500094
	(c) Wang, L.; Zhou, J.; Tang, Y. Chin. J. Chem. 2018, 36, 1123. doi: 10.1002/cjoc.v36.12
[11]	For recent examples, see: (a) Liu, H.-K.; Wang, S. R.; Song, X.-Y.; Zhao, L.-P.; Wang, L.; Tang, Y. Angew. Chem., Int. Ed. 2019, 58, 4345. doi: 10.1002/anie.v58.13
	(b) Zheng, Z.-B.; Cheng, W.-F.; Wang, L.; Zhu, J.; Sun, X.-L.; Tang, Y. Chin. J. Chem. 2020, 38, 1629. doi: 10.1002/cjoc.v38.12
[12]	For selected examples of indoles with cyclopropanes, see: (a) Harrington, P.; Kerr, M. A. Tetrahedron Lett. 1997, 38, 5949. doi: 10.1016/S0040-4039(97)01351-8 pmid: 23651295
	(b) Kerr, M. A.; Keddy, R. G. Tetrahedron Lett. 1999, 40, 5671. doi: 10.1016/S0040-4039(99)01107-7 pmid: 23651295
	(c) England, D. B.; Kuss, T. D. O.; Keddy, R. G.; Kerr, M. A. J. Org. Chem. 2001, 66, 4704. pmid: 23651295
	(d) Bajtos, B.; Yu, M.; Zhao, H.; Pagenkopf, B. L. J. Am. Chem. Soc. 2007, 129, 9631. doi: 10.1021/ja067821+ pmid: 23651295
	(e) Wales, S. M.; Walker, M. M.; Johnson, J. S. Org. Lett. 2013, 15, 2558. doi: 10.1021/ol4010646 pmid: 23651295
	(f) Xiong, H.; Xu, H.; Liao, S.; Xie, Z.; Tang, Y. J. Am. Chem. Soc. 2013, 135, 7851. doi: 10.1021/ja4042127 pmid: 23651295
	(g) Liu, Q. J.; Yan, W. G.; Wang, L.; Zhang, X. P.; Tang, Y. Org. Lett. 2015, 17, 4014. doi: 10.1021/acs.orglett.5b01909 pmid: 23651295
	(h) Yan, W.-G.; Wang, P.; Wang, L.; Sun, X.-L.; Tang, Y. Acta Chim. Sinica 2017, 75, 783. (in Chinese) doi: 10.6023/A17040146 pmid: 23651295
	(严文广, 王盼, 王丽佳, 孙秀丽, 唐勇, 化学学报, 2017, 75, 783.) doi: 10.6023/A17040146 pmid: 23651295
[13]	(a) Zheng, C.; Wu, Q.-F.; You, S.-L. J. Org. Chem. 2013, 78, 4357. doi: 10.1021/jo400365e pmid: 23578142
	(b) Zheng, C.; Xia, Z.-L.; You, S.-L. Chem 2018, 4, 1952. doi: 10.1016/j.chempr.2018.06.006 pmid: 23578142
[14]	Zhu, J.; Liang, Y.; Wang, L.; Zheng, Z. B.; Houk, K. N.; Tang, Y. J. Am. Chem. Soc. 2014, 136, 6900. doi: 10.1021/ja503117q

[1]	陈健强, 朱钢国, 吴劼. 镍催化氮杂环丙烷的开环偶联反应研究[J]. 化学学报, 2024, 82(2): 190-212.
[2]	张艳东, 朱守非. 环丙烷骨架膦配体的研究展望^★[J]. 化学学报, 2023, 81(7): 777-783.
[3]	宋晓宁, 杨杉, 汪欣, 王芒. 甲基酮的二氟同系化-卤化反应:一锅法合成β-卤代-α,α-二氟代酮[J]. 化学学报, 2018, 76(12): 983-987.
[4]	严文广, 王盼, 王丽佳, 孙秀丽, 唐勇. 铜(II)催化的吲哚与四取代D-A环丙烷[3+2]开环/环化反应[J]. 化学学报, 2017, 75(8): 783-787.
[5]	赵金钵, 张前. 配位导向的分子内C(sp³)-H键胺化反应构建含氮杂环的新进展[J]. 化学学报, 2015, 73(12): 1235-1244.
[6]	詹益周, 王宝雷, 张丽媛, 张燕, 张晓, 李正名, 宋海斌. 基于Ugi反应的含芳氨基甲酰基1-氰基-1-环丙烷甲酰胺类新化合物的合成、结构和生物活性研究[J]. 化学学报, 2015, 73(11): 1173-1181.
[7]	耿志远,张兴辉,王永成,方冉,高立国,陈晓霞,赵存元. 钐(II)类卡宾CH₃SmCH₂I与乙烯环丙烷化反应及溶剂化效应的理论研究[J]. 化学学报, 2006, 64(8): 772-778.
[8]	王建平,程习星,陈庆华. 某些官能化手性氮杂环丙烷衍生物的合成及其结构[J]. 化学学报, 2006, 64(7): 686-690.
[9]	李志成,陈志勇,胡文浩,余孝其. 铑(II)催化重氮苄基膦酸酯与芳香亚胺的氮杂环丙烷化反应[J]. 化学学报, 2005, 63(12): 1136-1140.
[10]	苏桂发, 潘成学, 牟红涛, 曾陇梅, 郁开北. 反式2,3-二芳基取代-1-氨基环丙烷羧酸的合成及其结构研究[J]. 化学学报, 2004, 62(19): 1941-1947.
[11]	陈德展,孔德信,张红雨. HMB体系分子内质子传递的量子化学计算研究[J]. 化学学报, 2002, 60(2): 234-240.
[12]	孙伟,夏春谷,王爱勤. 壳聚糖希夫碱铜多相催化剂催化苯乙烯环丙烷化反应研究[J]. 化学学报, 2002, 60(1): 162-165.
[13]	福州大学化学系. 不对称方酸染料的电子结构与光导性的从头算研究[J]. 化学学报, 2001, 59(6): 847-852.
[14]	黄敏,张熊禄,黄海洪,陈庆华. 手性螺-环丙烷化合物中手性辅基的区域性转换反应的研究[J]. 化学学报, 2001, 59(11): 2000-2006.
[15]	黄慧,陈庆华. 光学活性螺-环丙烷双内酯化合物的合成[J]. 化学学报, 2000, 58(2): 248-252.

吲哚-环丙烷的分子内开环反应^※

Intramolecular Ring-opening of Indole-cyclopropanes^※

RichHTML

PDF

补充材料

可视化

摘要/Abstract

引用此文

分享此文

图/表 4

参考文献 14

相关文章 15

编辑推荐

相关统计

本文评价

吲哚-环丙烷的分子内开环反应※

Intramolecular Ring-opening of Indole-cyclopropanes※

RichHTML

PDF

补充材料

可视化

摘要/Abstract

引用此文

分享此文

图/表 4

参考文献 14

相关文章 15

编辑推荐

相关统计

本文评价

吲哚-环丙烷的分子内开环反应^※

Intramolecular Ring-opening of Indole-cyclopropanes^※