Citation: Liu Qingquan, Hu Xiangguo. Application of Benzylic C-H Fluorination for the Formal Synthesis of syn-α, β-Difluoro-γ-amino Acid[J]. Chinese Journal of Organic Chemistry, ;2018, 38(6): 1525-1529. doi: 10.6023/cjoc201712020 shu

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

Liu Qingquan ,
Hu Xiangguo ^,

National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022

Corresponding author: Hu Xiangguo, huxiangg@iccas.ac.cn
Received Date: 13 December 2017
Revised Date: 19 January 2018
Available Online: 6 June 2018
Fund Project: the National Natural Science Foundation of China 21502076the Outstanding Young Talents Scheme of Jiangxi Province 20171BCB23039Project supported by the National Natural Science Foundation of China (No. 21502076) and the Outstanding Young Talents Scheme of Jiangxi Province (No. 20171BCB23039)

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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.
- C-H fluorination,
- organofluorine,
- amino acid
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