Synthesis of α-Aryl Nitriles via Nucleophilic Substitution of α-Cyanohydrin Methanesulfonates with Malonates

doi:10.6023/cjoc202208029

Chinese Journal of Organic Chemistry ›› 2023, Vol. 43 ›› Issue (2): 668-678.DOI: 10.6023/cjoc202208029 Previous Articles Next Articles

α-氰醇甲磺酸酯与丙二酸酯的亲核取代反应合成α-芳基腈类化合物

王雷刚^a, 郑逸轩^a, 周希^a, 王海峰^a, 严琼姣^a, 汪伟^a^,^*(), 陈芬儿^a^,^b^,^*()

a 武汉工程大学药物研究院武汉 430205
b 复旦大学化学学院上海 200433

收稿日期:2022-08-23 修回日期:2022-10-03 发布日期:2022-10-31
基金资助:
国家自然科学基金(21602144); 湖北省教育厅科研计划(Q20211503)

Synthesis of α-Aryl Nitriles via Nucleophilic Substitution of α-Cyanohydrin Methanesulfonates with Malonates

Leigang Wang^a, Yixuan Zheng^a, Xi Zhou^a, Haifeng Wang^a, Qiongjiao Yan^a, Wei Wang^a(), Fener Chen^a^,^b()

a Pharmaceutical Research Institute, Wuhan Institute of Technology, Wuhan 430205
b Department of Chemistry, Fudan University, Shanghai 200433

Received:2022-08-23 Revised:2022-10-03 Published:2022-10-31
Contact: *E-mail: wang520520wei@163.com;rfchen@fudan.edu.cn
Supported by:
National Natural Science Foundation of China(21602144); Scientific Research Project of Education Department of Hubei Province(Q20211503)

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Abstract

An efficient synthesis of α-aryl nitriles via nucleophilic substitution of α-cyanohydrin methanesulfonates with malonates is developed. This transition metal-free protocol has the advantages of cheap and easily available starting materials, mild reaction conditions, simple operation, a broad substrate scope and high functional group tolerance. Furthermore, this strategy could also be used to asymmetric malonates and acyl esters.

Key words: α-aryl nitriles, α-cyanohydrin methanesulfonates, malonates, nucleophilic substitution

Cite this article

Leigang Wang, Yixuan Zheng, Xi Zhou, Haifeng Wang, Qiongjiao Yan, Wei Wang, Fener Chen. Synthesis of α-Aryl Nitriles via Nucleophilic Substitution of α-Cyanohydrin Methanesulfonates with Malonates[J]. Chinese Journal of Organic Chemistry, 2023, 43(2): 668-678.

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Fig. & Tab. 6

References 20

[1]	(a) Fleming, F. F. Nat. Prod. Rep. 1999, 16, 597. doi: 10.1039/a804370a pmid: 20804202
	(b) Fleming, F. F.; Yao, L.; Ravikumar, P. C.; Funk, L.; Shook, B. C. J. Med. Chem. 2010, 53, 7902. doi: 10.1021/jm100762r pmid: 20804202
	(c) Wang, J.; Liu, H. Chin. J. Org. Chem. 2012, 32, 1643. (in Chinese) doi: 10.6023/cjoc1202132 pmid: 20804202
	(王江, 柳红, 有机化学, 2012, 32, 1643.) doi: 10.6023/cjoc1202132 pmid: 20804202
	(d) Cohen, D. T.; Buchwald, S. L. Org. Lett. 2015, 17, 202. doi: 10.1021/ol5032359 pmid: 20804202
	(e) Yan, G.; Zhang, Y.; Wang, J. Adv. Synth. Catal. 2017, 359, 4068. doi: 10.1002/adsc.201700875 pmid: 20804202
	(f) Que, X.; Qiu, Z.; Yan, Y. High Perform. Polym. 2019, 31, 1062. doi: 10.1177/0954008318821710 pmid: 20804202
[2]	(a) Daw, P.; Sinha, A.; Rahaman, S. M. W.; Dinda, S.; Bera, J. K. Organometallics 2012, 31, 3790. doi: 10.1021/om300297y
	(b) Kumar, S.; Dixit, S. K.; Awasthi, S. K. Tetrahedron Lett. 2014, 55, 3802. doi: 10.1016/j.tetlet.2014.05.050
	(c) Tomás-Mendivil, E.; Suárez, F. J.; Díez, J.; Cadierno, V. Chem. Commun. 2014, 50, 9661. doi: 10.1039/C4CC04058A
	(d) Manikandan, R.; Anitha, P.; Prakash, G.; Vijayan, P.; Viswanathamurthi, P.; Butcher, R. J.; Malecki, J. G. J. Mol. Catal. A: Chem. 2015, 398, 312. doi: 10.1016/j.molcata.2014.12.017
	(e) Marcé, P.; Lynch, J.; Blacker, A. J.; Williams, J. M. J. Chem. Commun. 2016, 52, 1436. doi: 10.1039/C5CC08714G
	(f) Singh, K.; Sarbajna, A.; Dutta, I.; Pandey, P.; Bera, J. K. Chem. Eur. J. 2017, 23, 7761. doi: 10.1002/chem.201700816
	(g) Ji, P.; Manna, K.; Lin, Z.; Feng, X.; Urban, A.; Song, Y.; Lin, W. J. Am. Chem. Soc. 2017, 139, 7004. doi: 10.1021/jacs.7b02394
	(h) Paul, A.; Chandak, H. S.; Ma, L.; Seidel, D. Org. Lett. 2020, 22, 976. doi: 10.1021/acs.orglett.9b04506
	(i) Li, C.; Chang, X.-Y.; Huo, L.; Tan, H.; Xing, X.; Xu, C. ACS Catal. 2021, 11, 8716. doi: 10.1021/acscatal.1c02254
	(j) Tong, S.; Li, K.; Ouyang, X.; Song, R.; Li, J. Green Synth. Catal. 2021, 2, 145.
[3]	Jackson, T.; Woo, L. W. L.; Trusselle, M. N.; Chander, S. K.; Purohit, A.; Reed, M. J.; Potter, B. V. L. Org. Biomol. Chem. 2007, 5, 2940. pmid: 17728860
[4]	Teodori, E.; Dei, S.; Garnier-Suillerot, A.; Gualtieri, F.; Manetti, D.; Martelli, C.; Romanelli, M. N.; Scapecchi, S.; Sudwan, P.; Salerno, M. J. Med. Chem. 2005, 48, 7426. doi: 10.1021/jm050542x
[5]	Noble, S.; McTavish, D. Drugs 1995, 50, 1032. pmid: 8612470
[6]	Culkin, D. A.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 9330. pmid: 12167001
[7]	Jiao, Z.; Chee, K. W.; Zhou, J. S. J. Am. Chem. Soc. 2016, 138, 16240. doi: 10.1021/jacs.6b11610
[8]	Qian, X.; Han, J.; Wang, L. Adv. Synth. Catal. 2016, 358, 940. doi: 10.1002/adsc.201501013
[9]	He, A.; Falck, J. R. J. Am. Chem. Soc. 2010, 132, 2524. doi: 10.1021/ja910582n
[10]	Nambo, M.; Yar, M.; Smith, J. D.; Crudden, C. M. Org. Lett. 2015, 17, 50. doi: 10.1021/ol503213z
[11]	Choi, J.; Fu, G. C. J. Am. Chem. Soc. 2012, 134, 9102. doi: 10.1021/ja303442q
[12]	Kadunce, N. T.; Reisman, S. E. J. Am. Chem. Soc. 2015, 137, 10480. doi: 10.1021/jacs.5b06466
[13]	(a) Wheeler, C.; West, K. N.; Liotta, C. L.; Eckert, C. A. Chem. Commun. 2001, 887.
	(b) Kim, D. W.; Song, C. E.; Chi, D. Y. J. Org. Chem. 2003, 68, 4281. doi: 10.1021/jo034109b
[14]	Ratani, T. S.; Bachman, S.; Fu, G. C.; Peters, J. C. J. Am. Chem. Soc. 2015, 137, 13902. doi: 10.1021/jacs.5b08452 pmid: 26491957
[15]	Chen, G.; Wang, Z.; Wu, J.; Ding, K. Org. Lett. 2008, 10, 4573. doi: 10.1021/ol801812a
[16]	Shirsath, S. R.; Shinde, G. H.; Shaikh, A. C.; Muthukrishnan, M. J. Org. Chem. 2018, 83, 12305. doi: 10.1021/acs.joc.8b01926 pmid: 30203649
[17]	Liu, S.; Meng, L.; Zeng, X.; Hammond, G. B.; Xu, B. Chin. J. Chem. 2021, 39, 913. doi: 10.1002/cjoc.202000579
[18]	(a) Ambrożak, A.; Steinebach, C.; Gardner, E. R.; Beedie, S. L.; Schnakenburg, G.; Figg, W. D.; Gütschow, M. ChemMedChem 2016, 11, 2621. doi: 10.1002/cmdc.201600496
	(b) Singh, A.; Hakk, H.; Lupton, S. J. J. Labelled Compd. Radiopharm. 2018, 61, 386. doi: 10.1002/jlcr.3597
	(c) Wang, L.-L.; Battini, N.; Bheemanaboina, R. R. Y.; Zhang, S.-L.; Zhou, C.-H. Eur. J. Med. Chem. 2019, 167, 105. doi: 10.1016/j.ejmech.2019.01.072
[19]	(a) Kiledal, S. A.; Jourdain, R.; Vellalath, S.; Romo, D. Org. Lett. 2021, 23, 6622. doi: 10.1021/acs.orglett.1c02044 pmid: 35862275
	(b) Cheng, F.; Chen, T.; Huang, Y.-Q.; Li, J.-W.; Zhou, C.; Xiao, X.; Chen, F.-E. Org. Lett. 2022, 24, 115. doi: 10.1021/acs.orglett.1c03688 pmid: 35862275
	(c) Moghadam, F. A.; Hicks, E. F.; Sercel, Z. P.; Cusumano, A. Q.; Bartberger, M. D.; Stoltz, B. M. J. Am. Chem. Soc. 2022, 144, 7983. doi: 10.1021/jacs.2c02960 pmid: 35862275
	(d) Wu, J.; Young, C. M.; Watts, A. A.; Slawin, A. M. Z.; Boyce, G. R.; Bühl, M.; Smith, A. D. Org. Lett. 2022, 24, 4040. doi: 10.1021/acs.orglett.2c01486 pmid: 35862275
	(e) Cochrane, S. R.; Kerr, M. A. Org. Lett. 2022, 24, 5509. doi: 10.1021/acs.orglett.2c01810 pmid: 35862275
[20]	(a) Ueda, M.; Nishimura, K.; Ryu, I. Synlett 2013, 24, 1683. doi: 10.1055/s-0033-1339199
	(b) Wu, G.; Xu, S.; Deng, Y.; Wu, C.; Zhao, X.; Ji, W.; Zhang, Y.; Wang, J. Tetrahedron 2016, 72, 8022. doi: 10.1016/j.tet.2016.10.031
	(c) Li, C.; Zhang, Y.; Sun, Q.; Gu, T.; Peng, H.; Tang, W. J. Am. Chem. Soc. 2016, 138, 10774. doi: 10.1021/jacs.6b06285

Entry	LG	Base	Solvent	Yield^b/%
1	OMs	LiOt-Bu	THF	50
2	OAc	LiOt-Bu	THF	0
3	OBoc	LiOt-Bu	THF	0
4	OPiv	LiOt-Bu	THF	0
5	OTs	LiOt-Bu	THF	40
6	OMs	LiOH	THF	52
7	OMs	NaOH	THF	15
8	OMs	DBU	THF	0
9	OMs	NaHMDS	THF	20
10	OMs	LiOH	1,4-Dioxane	72
11	OMs	LiOH	MeCN	76
12	OMs	LiOH	EtOAc	53
13	OMs	LiOH	Toluene	24
14	OMs	LiOH	IPA	88
15	OMs	-	IPA	0
16^c	OMs	LiOH	IPA	59
17^d	OMs	LiOH	IPA	95

Entry	LG	Base	Solvent	Yield^b/%
1	OMs	LiOt-Bu	THF	50
2	OAc	LiOt-Bu	THF	0
3	OBoc	LiOt-Bu	THF	0
4	OPiv	LiOt-Bu	THF	0
5	OTs	LiOt-Bu	THF	40
6	OMs	LiOH	THF	52
7	OMs	NaOH	THF	15
8	OMs	DBU	THF	0
9	OMs	NaHMDS	THF	20
10	OMs	LiOH	1,4-Dioxane	72
11	OMs	LiOH	MeCN	76
12	OMs	LiOH	EtOAc	53
13	OMs	LiOH	Toluene	24
14	OMs	LiOH	IPA	88
15	OMs	-	IPA	0
16^c	OMs	LiOH	IPA	59
17^d	OMs	LiOH	IPA	95

α-氰醇甲磺酸酯与丙二酸酯的亲核取代反应合成α-芳基腈类化合物

Synthesis of α-Aryl Nitriles via Nucleophilic Substitution of α-Cyanohydrin Methanesulfonates with Malonates

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