镍催化吡啶/喹啉鎓盐分子内去芳构化芳基加成反应

doi:10.6023/cjoc202302016

摘要/Abstract

发展了溴化镍催化下吡啶/喹啉鎓盐与溴代芳烃的分子内去芳构化加成反应. 在锌粉作还原剂条件下, 镍催化的溴代芳烃与吡啶/喹啉鎓盐碳氮双键的分子内Grignard型加成反应顺利发生, 实现了吡啶/喹啉的去芳构化, 并以中等至良好的收率合成了一系列具有二氢吡啶/二氢喹啉结构单元的螺环吲哚酮类化合物.

关键词: 吡啶, 喹啉, 芳基化, 去芳构化, 镍

A nickel-catalyzed intramolecular dearomative arylation reaction of pyridiniums and quinoliniums is developed. In the presence of zinc powder as a reducing agent, the intramolecular Grignard-type addition of arylbromides to the C=N bonds of pyridiniums and quinoliniums proceeds smoothly to render pyridines and quinolines dearomatization, leading to a range of spirooxindole derivatives bearing dihydropyridine and dihydroquinoline moieties in moderate to good yields.

Key words: pyridine, quinoline, arylation, dearomatization, nickel

引用此文

芦军, 李奇闯, 梁仁校, 贾义霞. 镍催化吡啶/喹啉鎓盐分子内去芳构化芳基加成反应[J]. 有机化学, 2023, 43(5): 1875-1882.

Jun Lu, Qichuang Li, Renxiao Liang, Yixia Jia. Nickel-Catalyzed Intramolecular Dearomative Arylation of Pyridiniums and Quinoliniums[J]. Chinese Journal of Organic Chemistry, 2023, 43(5): 1875-1882.

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

分享此文

图/表 8

图1. 含哌啶/四氢喹啉螺环吲哚酮结构的生物活性分子

Figure 1. Bioactive molecules having spirooxindole frameworks bearing piperidines/tetraquinolines

图式1. 过渡金属催化吡啶/喹啉鎓盐的去芳构化加成反应

Scheme 1. Transition-metal-catalyzed dearomative addition of pyridinium/quinoliniums

Entry	Solvent	Catalyst	Ligand	Yield^b/%
1	THF	Ni(PPh₃)₂Br₂	Bpy	55
2	DMF	Ni(PPh₃)₂Br₂	Bpy	0
3	MeOH	Ni(PPh₃)₂Br₂	Bpy	0
4	Dioxane	Ni(PPh₃)₂Br₂	Bpy	62
5	Dioxane	NiBr₂•DME	Bpy	<5
6	Dioxane	Ni(PCy₃)₂Cl₂	Bpy	46
7^c	Dioxane	Ni(PPh₃)₂Br₂	Bpy	52
8^d	Dioxane	Ni(PPh₃)₂Br₂	Bpy	48
9	Dioxane	Ni(PPh₃)₂Br₂	1,10-Phen	65
10	Dioxane	Ni(PPh₃)₂Br₂	L1	55
11	Dioxane	Ni(PPh₃)₂Br₂	L2	60
12	Dioxane	Ni(PPh₃)₂Br₂	L3	58
13^e	Dioxane	Ni(PPh₃)₂Br₂	DMAP	62
14^f	Dioxane	Ni(PPh₃)₂Br₂	DMAP	71
15^g	Dioxane	Ni(PPh₃)₂Br₂	DMAP	0
16^h	Dioxane	Ni(PPh₃)₂Br₂	DMAP	0
17	Dioxane		DMAP	0

表1. 反应条件优化a

Table 1. Condition optimization

表2. 吡啶鎓盐的底物范围a

Table 2. Substrate scope of the pyridiniums

表3. 喹啉鎓盐去芳构化芳基化反应的底物范围a

Table 3. Substrate scope of the dearomative arylation of quinoliniums

图式2. 镍催化喹啉鎓盐分子内去芳构化烯基加成反应

Scheme 2. Nickel-catalyzed intramolecular alkenylative dearo- matization of of quinoliniums

图式3. 产物4a的克级规模合成及氢化

Scheme 3. Gram-scale synthesis and the hydrogenation of product 4a

图式4. 可能的反应机理

Scheme 4. Possible mechanism

参考文献 19

[1]	(a) Kouznetsov, V. V.; Arenas, D. R. M.; Arvelo, F.; Forero, J. S. B.; Sojo, F.; Munoz, A. Lett. Drug Des. Discovery 2010, 7, 632. doi: 10.2174/157018010792929577
	(b) Rottmann, M.; McNamara, C.; Yeung, B. S. K.; Lee, M. C. S.; Zou, B.; Russell, B.; Seitz, P.; Plouffe, D. M.; Dharia, N. V.; Tan, J.; Cohen, S. B.; Spencer, K. R.; Gonzalez-Paez, G.; Lakshiminarayana, S. B.; Goh, A.; Suwanarusk, R.; Jegla, T.; Schmitt, E. K.; Beck, H.-P.; Brun, R.; Nosten, F.; Renia, L.; Dartois, V.; Keller, T. H.; Fidock, D. A.; Winzeler, E. A.; Diagana, T. T. Science 2010, 329, 1175. doi: 10.1126/science.1193225
	(c) Yeung, B. K. S.; Zou, B.; Rottmann, M.; Lakshminarayana, S. B.; Ang, S. H.; Leong, S. Y.; Tan, J.; Wong, J.; Keller-Maerki, S.; Fischli, C.; Goh, A.; Schmitt, E. K.; Krastel, P.; Francotte, E.; Kuhen, K.; Plouffe, D.; Henson, K.; Wagner, T.; Winzeler, E. A.; Petersen, F.; Brun, R.; Dartois, V.; Diagana, T. T.; Keller, T. H. J. Med. Chem. 2010, 53, 5155. doi: 10.1021/jm100410f
	(d) Lesma, G.; Landoni, N.; Sacchetti, A.; Silvani, A. Tetrahedron 2010, 66, 4474. doi: 10.1016/j.tet.2010.04.077
	(e) Ding, Q.; Liu, J.-J.; Zhang, Z. WO 2007104714, 2007.
[2]	(a) Kim, J.; Park, S. Y.; Jung, M.; Jang, W. C.; Ko, H. M. Tetrahedron Lett. 2022, 88, 153512. doi: 10.1016/j.tetlet.2021.153512
	(b) Jang, W. C.; Jung, M.; Ko, H. M. Org. Lett. 2021, 23, 1510. doi: 10.1021/acs.orglett.1c00292
	(c) Wang, C.-H.; Reilly, J.; Brand, N.; Schwartz, S.; Alluri, S.; Chan, T.-M.; Buevich, A. V.; Ganguly, A. K. Tetrahedron Lett. 2021, 51, 6213. doi: 10.1016/j.tetlet.2010.09.010
[3]	(a) Hajra, S.; Jana, B. Org. Lett. 2017, 19, 4778. doi: 10.1021/acs.orglett.7b02150
	(b) Yang, M.-C.; Peng, C.; Huang, H.; Yang, L.; He, X.-H.; Huang, W.; Cui, H.-L.; He, G.; Han, B. Org. Lett. 2017, 19, 6752. doi: 10.1021/acs.orglett.7b03516
	(c) Homquist, M.; Blay, G.; Muñoz, M. C.; Pedro, J. R. Adv. Synth. Catal. 2015, 357, 3857. doi: 10.1002/adsc.201500716
[4]	Nakamura, S.; Matsuzaka, K.; Hatanaka, T.; Funahashi, Y. Org. Lett. 2020, 22, 2868. doi: 10.1021/acs.orglett.0c00289 pmid: 32049543
[5]	Chang, Z.; Ye, C.; Fu, J.; Chigumbu, P.; Zeng, X.; Wang, Y.; Jiang, C.; Han, X. Adv. Synth. Catal. 2019, 361, 5516. doi: 10.1002/adsc.v361.24
[6]	(a) Wang, Y.-H.; Tian, J.-S.; Tan, P.-W.; Cao, Q.; Zhang, X.-X., Cao, Z.-Y.; Zhou, F.; Wang, X.; Zhou, J. Angew. Chem., Int. Ed. 2020, 59, 1634. doi: 10.1002/anie.v59.4
	(b) Wang, Y.; Ready, J. M. Org. Lett. 2012, 14, 2308. doi: 10.1021/ol300724c
[7]	(a) Bianchini, G.; Ribelles, P.; Becerra, D.; Ramosa, M. T.; Menéndez, J. C. Org. Chem. Front. 2016, 3, 412. doi: 10.1039/C6QO00037A
	(b) Gao, H.; Sun, J.; Yan, C.-G. Synthesis 2014, 46, 489. doi: 10.1055/s-00000084
	(c) Zhang, H.-H.; Sun, X.-X.; Liang, J.; Wang, Y.-M.; Zhao, C.-C.; Shi, F. Org. Biomol. Chem. 2014, 12, 9539. doi: 10.1039/C4OB01741B
	(d) Shi, F.; Xing, G.-J.; Zhu, R.-Y.; Tan, W.; Tu, S. Org. Lett. 2013, 15, 128. doi: 10.1021/ol303154k
	(e) Kouznetsov, V. V.; Forero, J. S. B.; Torres, D. F. A. Tetrahedron Lett. 2008, 49, 5855. doi: 10.1016/j.tetlet.2008.07.096
[8]	Wang, X.-W.; Huang, W.-J.; Wang, H.; Wu, B.; Zhou, Y.-G. Org. Lett. 2022, 24, 1727. doi: 10.1021/acs.orglett.2c00368
[9]	(a) Gao, Y.-T.; Jin, X.-Y.; Liu, Q.; Liu, A.-D.; Cheng, L.; Wang, D.; Liu, L. Molecules 2018, 23, 2265. doi: 10.3390/molecules23092265
	(b) Ohmatsu, K.; Ando, Y.; Nakashima, T.; Ooi, T. Chem 2016, 1, 802. doi: 10.1016/j.chempr.2016.10.012
	(c) Fuchs, J. R.; Funk, R. L. Org. Lett. 2005, 7, 677. doi: 10.1021/ol047532v
[10]	(a) Mu, B.-S.; Zhang, Z.-H.; Wu, W.-B.; Yu, J.-S.; Zhou, J. Acta Chim. Sinica 2021, 79, 685. (in Chinese) doi: 10.6023/A21040131
	(穆博帅, 张志豪, 武文彪, 余金生, 周剑, 化学学报, 2021, 79, 685.) doi: 10.6023/A21040131
	(b) Bertuzzi, G.; Bernardi, L.; Fochi, M. Catalysts 2018, 8, 632. doi: 10.3390/catal8120632
	(c) Ding, Q.; Zhou, X.; Fan, R. Org. Biomol. Chem. 2014, 12, 4807. doi: 10.1039/C4OB00371C
	(d) Ahamed, M.; Todd, M. H. Eur. J. Org. Chem. 2010, 5935.
[11]	(a) Pappoppula, M.; Cardoso, F. S. P.; Garrett, B. O.; Aponick, A. Angew. Chem., Int. Ed. 2015, 54, 15202. doi: 10.1002/anie.201507848 pmid: 26514098
	(b) Black, D. A.; Beveridge, R. E.; Arndtsen, B. A. J. Org. Chem. 2008, 73, 1906. doi: 10.1021/jo702293h pmid: 26514098
	(c) Sun, Z.; Yu, S.; Ding, Z.; Ma, D. J. Am. Chem. Soc. 2007, 129, 9300. doi: 10.1021/ja0734849 pmid: 26514098
	(d) Taylor, A. M.; Schreiber, S. L. Org. Lett. 2006, 8, 143. doi: 10.1021/ol0526165 pmid: 26514098
[12]	(a) Guo, Y.; Reis, M. C.; Kootstra, J.; Harutyunyan, S. R. ACS Catal. 2021, 11, 8476. doi: 10.1021/acscatal.1c01544
	(b) Fernandez-Ibanez, M. A.; Macia, B.; Pizzuti, M. G.; Minnaard, A. J.; Feringa, B. L. Angew. Chem., Int. Ed. 2009, 48, 9339. doi: 10.1002/anie.v48:49
[13]	(a) Lutz, J. P.; Chau, S. T.; Doyle, A. G. Chem. Sci. 2016, 7, 4105. doi: 10.1039/C6SC00702C
	(b) Chau, S. T.; Lutz, J. P.; Wu, K.; Doyle, A. G. Angew. Chem., Int. Ed. 2013, 52, 9153. doi: 10.1002/anie.201303994
[14]	(a) Robinson, D. J.; Spurlin, S. P.; Gorden, J. D.; Karimov, R. R. ACS Catal. 2020, 10, 51. doi: 10.1021/acscatal.9b03874 pmid: 26879692
	(b) Wang, Y.; Liu, Y.; Zhang, D.; Wei, H.; Shi, M.; Wang, F. Angew. Chem., Int. Ed. 2016, 55, 3776. doi: 10.1002/anie.201511663 pmid: 26879692
	(c) Nadeau, C.; Aly, S.; Belyk, K. J. Am. Chem. Soc. 2011, 133, 2878. doi: 10.1021/ja111540g pmid: 26879692
[15]	(a) Yang, P.; Wang, Q.; Cui, B.-H.; Zhang, X.-D.; Liu, H.; Zhang, Y.-Y.; Liu, J.-L.; Huang, W.-Y.; Liang, R.-X.; Jia, Y.-X. J. Am. Chem. Soc. 2022, 144, 1087. doi: 10.1021/jacs.1c11092
	(b) Lou, S.-J.; Luo, G.; Yamaguchi, S.; An, K.; Nishiura, M.; Hou, Z. J. Am. Chem. Soc. 2021, 143, 20462. doi: 10.1021/jacs.1c10743
[16]	Zhang, M.; Chen, B.; Ge, C.; Liu, R.; Gao, J.; Jia, Y. Chin. J. Org. Chem. 2016, 36, 1636. (in Chinese) doi: 10.6023/cjoc201602007
	(张鸣頔, 陈斌, 葛晨, 刘人荣, 高建荣, 贾义霞, 有机化学, 2016, 36, 1636.) doi: 10.6023/cjoc201602007
[17]	Zhang, M.; Liu, R.; Gao, J.; Jia, Y. Chin. J. Org. Chem. 2017, 37, 652. (in Chinese) doi: 10.6023/cjoc201610009
	(张鸣頔, 刘人荣, 高建荣, 贾义霞, 有机化学, 2017, 37, 652.) doi: 10.6023/cjoc201610009
[18]	(a) Zhu, Z.; Xiao, J.; Li, M.; Shi, Z. Angew. Chem., Int. Ed. 2022, 61, e2022013.
	(b) Jiang, X.; Jiang, H.; Yang, Q.; Cheng, Y.; Lu, L.-Q.; Tunge, J. A.; Xiao, W.-J. J. Am. Chem. Soc. 2022, 144, 8347. doi: 10.1021/jacs.2c02481
[19]	Heinz, C.; Lutz, J. P.; Simmons, E. M.; Miller, M. M.; Ewing, W. R.; Doyle, A. G. J. Am. Chem. Soc. 2018, 140, 2292. doi: 10.1021/jacs.7b12212