Copper-Catalyzed Asymmetric Allyl Alkylation Using Grignard Reagents under Continuous Flow

doi:10.6023/cjoc202303027

Chinese Journal of Organic Chemistry ›› 2023, Vol. 43 ›› Issue (9): 3174-3179.DOI: 10.6023/cjoc202303027 Previous Articles Next Articles

铜催化格氏试剂的不对称烯丙基烷基化连续流反应

宋晓^a, 卿晶^b, 黎君^a, 贾雪雷^a^,^b, 吴福松^a, 黄均荣^a^,^*(), 金剑^c^,^*(), 游恒志^a^,^*()

a 哈尔滨工业大学(深圳)理学院深圳 518055
b 深圳市中核海得威生物科技有限公司深圳 518055
c 哈尔滨工业大学(深圳)实验与创新实践教育中心深圳 518055

收稿日期:2023-03-20 修回日期:2023-04-24 发布日期:2023-06-13
作者简介:^† 共同第一作者.
基金资助:
深圳市基础研究专项(JCYJ20190806142203709); 深圳市基础研究专项(JSGG20191129114029286); 深圳市基础研究专项(JSGG20201103153807021); 深圳市基础研究专项(GXWD2022081117373600); 广东省基础与应用基础研究基金(2021A1515110366); 中国博士后科学基金(2022M720951); 深圳市先进功能碳基材料研究与综合应用重点实验室资助项目

Copper-Catalyzed Asymmetric Allyl Alkylation Using Grignard Reagents under Continuous Flow

Xiao Song^a, Jing Qing^b, Jun Li^a, Xuelei Jia^a^,^b, Fusong Wu^a, Junrong Huang^a(), Jian Jin^c(), Hengzhi You^a()

a School of Science, Harbin Institute of Technology (Shenzhen), Shenzhen 518055
b Shenzhen Zhonghe Headway Bio-Sci & Tech Co., Ltd., Shenzhen 518055
c Education Center of Experiments and Innovations, Harbin Institute of Technology (Shenzhen), Shenzhen 518055

Received:2023-03-20 Revised:2023-04-24 Published:2023-06-13
Contact: * E-mail: youhenzhi@hit.edu.cn;hjunrong@hit.edu.cn;jianjin@hit.edu.cn
About author:^† These authors contributed equally to this work.
Supported by:
Shenzhen Basic Research Foundation(JCYJ20190806142203709); Shenzhen Basic Research Foundation(JSGG20191129114029286); Shenzhen Basic Research Foundation(JSGG20201103153807021); Shenzhen Basic Research Foundation(GXWD2022081117373600); Guangdong Basic and Applied Basic Research Foundation(2021A1515110366); China Postdoctoral Science Foundation(2022M720951); Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application

1. .pdf(1217KB)

Abstract

Continuous flow reactors were used to explore the copper-catalyzed asymmetric allyl alkylation (AAA) reactions of Grignard reagents under milder conditions for the first time. After continuous optimization, a 2-channel stainless steel broken-line continuous flow reactor was used to achieve a copper-catalyzed AAA reaction of various Grignard reagents at –20~–10 ℃ under very short reaction retention time of 0.6 s furnishing the corresponding products in 82%~99% yields with moderate to good enantioselectivity. Furthermore, the copper-catalyzed AAA reaction of 3-bromocyclohexene with methylmagnesium bromide was scaled up under a continuous flow process with continuous feeding for 34 min affording 0.968 g of (S)-3-methylcyclohex-1-ene with 98.7% yield and 96.6% ee.

Key words: continuous flow, micro reactors, copper-catalysis, asymmetric allyl alkylation, gram-scale preparation

Cite this article

Xiao Song, Jing Qing, Jun Li, Xuelei Jia, Fusong Wu, Junrong Huang, Jian Jin, Hengzhi You. Copper-Catalyzed Asymmetric Allyl Alkylation Using Grignard Reagents under Continuous Flow[J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3174-3179.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 6

References 9

[10]	Lin H.; Dai C.; Jamison T. F.; Jensen K. F. Angew. Chem., Int. Ed. 2017, 56, 8870. doi: 10.1002/anie.v56.30
[11]	Yao H.; Wan L.; Zhao X.; Guo Y.; Zhou J.; Bo X.; Mao Y.; Xin Z. Org. Process Res. Dev. 2021, 25, 2060. doi: 10.1021/acs.oprd.1c00105
[12]	Liao J.; Zhang S.; Wang Z.; Song X.; Zhang D.; Kumar R.; Jin J.; Ren P.; You H.; Chen F. Green Synth. Catal. 2020, 1, 121.
[13]	Coley C. W.; Thomas D. A.; Lummiss J.; Jaworski J. N.; Jensen K. F. Science 2019, 365, eaax1566. doi: 10.1126/science.aax1566
[14]	Zisu B.; Bhaskaracharya R.; Kentish S.; Ashokkumar M. Ultrason. Sonochem. 2010, 17, 1075. doi: 10.1016/j.ultsonch.2009.10.014
[15]	You H.; Rideau E.; Sidera M.; Fletcher S. Nature 2015, 517, 351. doi: 10.1038/nature14089
[1]	Trost B. M.; Crawley M. L. Chem. Rev. 2003, 103, 2921. doi: 10.1021/cr020027w
[2]	Cui P. L.; Liu H. Y.; Zhang D. N.; Wang C. Chin. J. Org. Chem. 2012, 32, 1401. (in Chinese) doi: 10.6023/cjoc1110071
	(崔朋雷, 刘海燕, 张冬暖, 王春, 有机化学, 2012, 32, 1401.) doi: 10.6023/cjoc1110071
[3]	Li J.; Song X.; Wu F.; You H.; Chen F.-E. Eur. J. Org. Chem. 2022, e202200860.
[4]	Klaveren M.; Persson E. S. M.; del Villar A.; Grove D. M.; Bäckvall J.-E.; van Koten G. Tetrahedron Lett. 1995, 36, 3059. doi: 10.1016/0040-4039(95)00426-D
[5]	Meuzelaar G. J.; Karlström A. S. E.; van Klaveren M.; Persson E. S. M.; del Villar A.; van Koten G.; Bäckvall J.-E. Tetrahedron 2000, 56, 2895. doi: 10.1016/S0040-4020(00)00145-9
[6]	Karlström A. S. E.; Huerta F. F.; Meuzelaar G. J.; Bäckvall J.-E. Synlett 2001, 2001(Special Issue),0923. doi: 10.1055/s-2001-14667
[7]	Langlois J.-B.; Alexakis A. Adv. Synth. Catal. 2010, 352, 447. doi: 10.1002/adsc.v352:2/3
[8]	Plutschack M. B.; Pieber B.; Gilmore K.; Seeberger P. H. Chem. Rev. 2017, 117, 11796. doi: 10.1021/acs.chemrev.7b00183 pmid: 28570059
[9]	Adamo A.; Beingessner R. L.; Behnam M.; Chen J.; Jamison T. F.; Jensen K. F.; Monbaliu J. C. M.; Myerson A. S.; Revalor E. M.; Snead D. R. Science 2016, 352, 61. doi: 10.1126/science.aaf1337

Entry	Time/s	CuX	Ligand	Solvent	Yield^c/%	ee^d/%
1^b	64	CuTc	L2	DCM	>99	48
2^e	64	CuTc	L2	DCM	>99	67
3^f	32	CuTc	L2	DCM	>99	69
4^g	16	CuTc	L2	DCM	>99	64
5^f	32	Cu(OTf)₂	L2	DCM	>99	61
6^f	32	CuBr	L2	DCM	>99	69
7^f	32	CuI	L2	DCM	>99	64
8^f	32	CuCN	L2	DCM	>99	51
9^f	32	CuCl	L2	DCM	>99	70
10^f	32	CuCl	L2	MTBE	>99	53
11^f	32	CuCl	L2	Hexane	>99	52
12^f	32	CuBr•SMe₂	L2	DCM	>99	70
13^f	32	CuBr•SMe₂	L1	DCM	>99	13
14^f	32	CuBr•SMe₂	L3	DCM	>99	42
15^f	32	CuBr•SMe₂	L4	DCM	>99	8

Entry	Time/s	CuX	Ligand	Solvent	Yield^c/%	ee^d/%
1^b	64	CuTc	L2	DCM	>99	48
2^e	64	CuTc	L2	DCM	>99	67
3^f	32	CuTc	L2	DCM	>99	69
4^g	16	CuTc	L2	DCM	>99	64
5^f	32	Cu(OTf)₂	L2	DCM	>99	61
6^f	32	CuBr	L2	DCM	>99	69
7^f	32	CuI	L2	DCM	>99	64
8^f	32	CuCN	L2	DCM	>99	51
9^f	32	CuCl	L2	DCM	>99	70
10^f	32	CuCl	L2	MTBE	>99	53
11^f	32	CuCl	L2	Hexane	>99	52
12^f	32	CuBr•SMe₂	L2	DCM	>99	70
13^f	32	CuBr•SMe₂	L1	DCM	>99	13
14^f	32	CuBr•SMe₂	L3	DCM	>99	42
15^f	32	CuBr•SMe₂	L4	DCM	>99	8

Entry^a	T^b/℃	Time/s	Yield^b/%	ee^c/%
1^d	r.t.	32	>99	70
2^a	r.t.	32	>99	59
3^a	r.t.	0.6	>99	74
4^a	0	0.6	>99	82
5^e	0	0.6	>99	71
6^f	0	0.6	>99	87
7^f^,^g	0	0.6	>99	85
8^f^,^g	–10	0.6	>99	96
9^f^,^g	–20	0.6	>99	97

Entry^a	T^b/℃	Time/s	Yield^b/%	ee^c/%
1^d	r.t.	32	>99	70
2^a	r.t.	32	>99	59
3^a	r.t.	0.6	>99	74
4^a	0	0.6	>99	82
5^e	0	0.6	>99	71
6^f	0	0.6	>99	87
7^f^,^g	0	0.6	>99	85
8^f^,^g	–10	0.6	>99	96
9^f^,^g	–20	0.6	>99	97

铜催化格氏试剂的不对称烯丙基烷基化连续流反应

Copper-Catalyzed Asymmetric Allyl Alkylation Using Grignard Reagents under Continuous Flow

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 6

References 9

Related Articles 13

Recommended Articles

Metrics

Comments

[1]	Kangbo Feng, Jiong Chen, Shuangxi Gu, Haifeng Wang, Fen'er Chen. New Progress of Fully Continuous Flow Reaction Technologies in Pharmaceutical Synthesis (2019~2022) [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 378-397.
[2]	Dandan Sui, Nannan Cen, Ruoqu Gong, Yang Chen, Wenbo Chen. Supporting-Electrolyte-Free Electrochemical Synthesis of Trifluoromethylated Oxindoles in Continuous Flow [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3239-3245.
[3]	Jingpeng Li, Shuntao Huang, Qi Yang, Weiqiang Li, Teng Liu, Chao Huang. A Practical Synthesis of (Z)-N-Vinyl Substituted N,O-Acetals under Continuous Flow Technology [J]. Chinese Journal of Organic Chemistry, 2023, 43(4): 1550-1558.
[4]	Chen Yang, Xuefeng Jia. Recent Advances in Copper-Catalyzed Boron-Reagent-Involved Multicomponent Difunctionalization of Alkenes [J]. Chinese Journal of Organic Chemistry, 2021, 41(6): 2280-2289.
[5]	Yahui Zhang, Wenjin Wu, Kexin Zhang, Shuangshuang Li, Wenyan Hao. A Rapid Synthesis of 5H-Benzo[d]imidazo[5,1-b][1,3]thiazines via Copper(I)-Catalyzed Cascade Bicyclization ofo-Alkynylphenyl Isothiocyanates with Ethyl (E)-2-(Benzylideneamino)acetates [J]. Chinese Journal of Organic Chemistry, 2021, 41(5): 1982-1990.
[6]	Ding Liu, Yuanyuan Zhu, Shuangxi Gu, Fener Chen. Application of Flow Chemistry in Halogenation [J]. Chinese Journal of Organic Chemistry, 2021, 41(3): 1002-1011.
[7]	Dun Zhou, Aihong Fan, Xiang Li, Chunxia Chen, Peng Sun, Jinsong Peng. Copper-Catalyzed Decarboxylative Cross-Coupling of Carboxylic Acids and Arylcarbamoyl Chlorides [J]. Chinese Journal of Organic Chemistry, 2021, 41(3): 1146-1152.
[8]	Suyan Zhao, Xueqin Gong, Ziyu Gan, Qiuli Yan, Xueliang Liu, Daoshan Yang. Efficient Copper-Catalyzed Domino Synthesis of Phosphonated Isoquinolin-1(2H)-ones Using Cyanomethylphosphonates as Building Blocks [J]. Chinese Journal of Organic Chemistry, 2021, 41(1): 258-266.
[9]	Zhang Yahui, Liu Yang, Miao Jiankang, Hao Wenyan. Copper-Catalyzed Cascade Bicyclization of o-Alkenylphenyl Isothiocyanates with Sodium Azide Leading to the 5H-Benzo[d]tetrazolo[5,1-b] [1,3]thiazines [J]. Chinese Journal of Organic Chemistry, 2020, 40(8): 2426-2432.
[10]	Lan Tianlei, Zhang Yue, Liu Wei, Xi Chanjuan, Chen Chao. Carbazolation Study of Active Arenes with Carbazole-Containing Hypervalent Iodine(III) Reagents [J]. Chinese Journal of Organic Chemistry, 2019, 39(8): 2166-2174.
[11]	Lei Lu, Li Chengjing, Mo Dongliang. Recent Advances in Copper-Catalyzed N-O Cleavage Strategy [J]. Chinese Journal of Organic Chemistry, 2019, 39(11): 2989-3012.
[12]	Cui Penglei, Liu Haiyan, Zhang Dongnuan, Wang Chun. Progress in Copper-Catalyzed Asymmetric Allylic Alkylation Reaction [J]. Chin. J. Org. Chem., 2012, 32(08): 1401-1409.
[13]	Liao Qian, Xi Chanjuan. Investigation on Copper-catalyzed Vinylation of N- and S-centered Nucleophiles [J]. Chin. J. Org. Chem., 2012, 32(06): 986-993.