Fluorinated cyclohexanes : synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif
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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.
Bykova , T , Al-Maharik , N , Slawin , A M Z & O'Hagan , D 2017 , ' Fluorinated cyclohexanes : synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif ' Beilstein Journal of Organic Chemistry , vol. 13 , pp. 728-733 . DOI: 10.3762/bjoc.13.72
Beilstein Journal of Organic Chemistry
© 2017 Bykova et al.; licensee Beilstein-Institut. This is an Open Access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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