Catalytic asymmetric transfer hydrogenation/dynamic kinetic resolution: an efficient synthesis of florfenicol

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• 作者：Xinlong Wang ; Lingjun Xu ; Lingjie Yan ; Haifeng Wang ; Sheng Han ; Yan Wu ; ^{wywin8@163.com" class="auth_mail" title="E-mail the corresponding author} ; Fener Chen ; ^{rfchen@fudan.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Florfenicol ; Asymmetric transfer hydrogenation ; Dynamic kinetic resolution ; Chloramphenicol base ; Inversion
• 刊名：Tetrahedron
• 出版年：2016
• 出版时间：7 April 2016
• 年：2016
• 卷：72
• 期：14
• 页码：1787-1793
• 全文大小：663 K

文摘

A robust and practical method has been developed for the synthesis of florfenicol (1) starting from commercial available 4-(methylsulfonyl) benzoic acid. The key step in this synthesis was the Ru-chloramphenicol base catalyzed asymmetric transfer hydrogenation of N-Boc α-amino-β-ketoester 5 through a dynamic kinetic resolution, which afforded the key chiral building block, anti-(2S,3S)-α-Boc-amino-β-hydroxyl ester 4, with high diastereoselectivity (92% de) and enantioselectivity (78% ee). The synthesis of a series of novel chloramphenicol base ligands L1–L10 is also included. This protocol could also be used for the asymmetric synthesis of fully synthetic analogs of florfenicol.