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


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,*()   

  1. 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 Songa, Jing Qingb, Jun Lia, Xuelei Jiaa,b, Fusong Wua, Junrong Huanga(), Jian Jinc(), Hengzhi Youa()   

  1. 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:;;
  • 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

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