摘要/Abstract

苄位C—H氟化已经成为一种向分子内引入氟原子的重要手段，然而，苄位C—H氟化反应还没有被应用到任何多步合成中.由于氟的构象效应，α，β-二氟代-γ-氨基酸在生物化学中有着重要的应用，但是其合成却具有一定的挑战性.在本文中，苄基C—H氟化作为关键步骤被成功用于syn-α，β-二氟代-γ-氨基酸1的形式合成.基于以下原因，本工作的合成路线比文献中的路线更为实用：（1）没有使用具有腐蚀性和毒性的亲核氟代试剂；（2）总收率为18%（以前的方法约为5%）；（3）关键苄位C—H反应被放大到了克量级.在对反应进行优化的过程中，观察到明显的氟效应，即对于苄位C—H氟化反应，邻位含有氟原子的碳比普通碳反应活性低很多.
关键词: C-H氟化, 有机氟, 氨基酸
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


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