Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif.
Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif.
复制标题
DOI：
10.3762/bjoc.13.72
复制
发表时间：
2017
影响因子：
2.7
通讯作者：
O'Hagan D
中科院分区：
文献类型：
--
作者：
Bykova T;Al-Maharik N;Slawin AMZ;O'Hagan D
本文报道了四氟环己基环系统的三个胺立体异构体5a-c的合成，作为发现化学计划的构建块。合成从苯甲腈的Birch还原开始，随后是原位碘甲烷淬灭。所得的2，5-环己二烯通过双环氧化和加氢开环反应进行。然后将所得氟代醇部分转化为四氟环己基环系统的不同立体异构体，然后将腈还原氢化，得到三种胺立体异构体。事实证明，有必要在环己烷环上放置一个甲基，以稳定化合物，防止随后的HF消除。两个全顺式四氟环己基异构体5a和5 b构成表面极化的环己烷环，氟在电负性面上，氢在电正性面上。
This paper reports the synthesis of three amine stereoisomers 5a–c of the tetrafluorocyclohexyl ring system, as building blocks for discovery chemistry programmes. The synthesis starts from a Birch reduction of benzonitrile, followed by an in situ methyl iodide quench. The resultant 2,5-cyclohexadiene was progressed via double epoxidations and then hydrofluorination ring opening reactions. The resultant fluorohydrin moieties were then converted to different stereoisomers of the tetrafluorocyclohexyl ring system, and then reductive hydrogenation of the nitrile delivered three amine stereoisomers. It proved necessary to place a methyl group on the cyclohexane ring in order to stabilise the compound against subsequent HF elimination. The two all-cis tetrafluorocyclohexyl isomers 5a and 5b constitute facially polarized cyclohexane rings, with fluorines on the electronegative face and hydrogens on the electropositive face.