Chin. J. Org. Chem. ›› 2018, Vol. 38 ›› Issue (6): 1525-1529.DOI: 10.6023/cjoc201712020 Previous Articles     Next Articles



刘清泉, 胡祥国   

  1. 江西师范大学国家单糖化学合成工程技术研究中心 南昌 330022
  • 收稿日期:2017-12-13 修回日期:2018-01-19 发布日期:2018-02-06
  • 通讯作者: 胡祥国,
  • 基金资助:


Application of Benzylic C-H Fluorination for the Formal Synthesis of syn-α, β-Difluoro-γ-amino Acid

Liu Qingquan, Hu Xiangguo   

  1. National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022
  • Received:2017-12-13 Revised:2018-01-19 Published:2018-02-06
  • Contact: 10.6023/cjoc201712020
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 21502076) and the Outstanding Young Talents Scheme of Jiangxi Province (No. 20171BCB23039).

Benzylic C-H fluorination has emerged as a valuable tool for the introduction of fluorine. However, the powerfulness of benzylic C-H fluorination has not been tested in any multi-step synthesis. α,β-Difluoro-γ-amino acids are useful entities for biological application owing to the so-called fluorine conformational effect. In this work, benzylic C-H fluorination has been successfully utilized as the key step for the formal synthesis of syn-α,β-difluoro-γ-amino acid 1, a very challenging but useful target. The approach developed in this work could be viewed as more practical compared to the previous one, because:(1) no corrosive and toxic nucleophilic fluorinating reagents are used, (2) the overall yield is 18% (the previous approach is about 5%), and (3) the key benzylic C-H reaction developed by Chen and co-workers was scaled up to one gram without decreasing its original efficiency. A striking fluorine effect was observed:a carbon with one fluorine atom on the adjacent carbon is much less reactive than an ordinary carbon for the benzylic C-H fluorination.

Key words: C-H fluorination, organofluorine, amino acid