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Chinese Journal of Organic Chemistry >

2023 , Vol. 43 >Issue 9: 3174 - 3179

DOI: https://doi.org/10.6023/cjoc202303027

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

  • Xiao Song ,
  • Jing Qing ,
  • Jun Li ,
  • Xuelei Jia ,
  • Fusong Wu ,
  • Junrong Huang ,
  • Jian Jin ,
  • Hengzhi You
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  • 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
† These authors contributed equally to this work.
* E-mail: ;
;

Received date: 2023-03-20

  Revised date: 2023-04-24

  Online published: 2023-06-14

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

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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 . DOI: 10.6023/cjoc202303027

References

[1]
Trost B. M.; Crawley M. L. Chem. Rev. 2003, 103, 2921.
[2]
Cui P. L.; Liu H. Y.; Zhang D. N.; Wang C. Chin. J. Org. Chem. 2012, 32, 1401. (in Chinese)
[2]
(崔朋雷, 刘海燕, 张冬暖, 王春, 有机化学, 2012, 32, 1401.)
[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.; B?ckvall J.-E.; van Koten G. Tetrahedron Lett. 1995, 36, 3059.
[5]
Meuzelaar G. J.; Karlstr?m A. S. E.; van Klaveren M.; Persson E. S. M.; del Villar A.; van Koten G.; B?ckvall J.-E. Tetrahedron 2000, 56, 2895.
[6]
Karlstr?m A. S. E.; Huerta F. F.; Meuzelaar G. J.; B?ckvall J.-E. Synlett 2001, 2001(Special Issue),0923.
[7]
Langlois J.-B.; Alexakis A. Adv. Synth. Catal. 2010, 352, 447.
[8]
Plutschack M. B.; Pieber B.; Gilmore K.; Seeberger P. H. Chem. Rev. 2017, 117, 11796.
[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.
[10]
Lin H.; Dai C.; Jamison T. F.; Jensen K. F. Angew. Chem., Int. Ed. 2017, 56, 8870.
[11]
Yao H.; Wan L.; Zhao X.; Guo Y.; Zhou J.; Bo X.; Mao Y.; Xin Z. Org. Process Res. Dev. 2021, 25, 2060.
[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.
[14]
Zisu B.; Bhaskaracharya R.; Kentish S.; Ashokkumar M. Ultrason. Sonochem. 2010, 17, 1075.
[15]
You H.; Rideau E.; Sidera M.; Fletcher S. Nature 2015, 517, 351.
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