All-cis 1,2,3,4,5,6-hexafluorocyclohexane is a facially polarized cyclohexane

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Abstract

The highest-energy stereoisomer of 1,2,3,4,5,6-hexafluorocyclohexane, in which all of the fluorines are ‘up’, is prepared in a 12-step protocol. The molecule adopts a classic chair conformation with alternate C–F bonds aligned triaxially, clustering three highly electronegative fluorine atoms in close proximity. This generates a cyclohexane with a high molecular dipole (μ = 6.2 D), unusual in an otherwise aliphatic compound. X-ray analysis indicates that the intramolecular Fax···Fax distances (2.77 Å) are longer than the vicinal Fax···Feq­ distances (2.73 Å) suggesting a tension stabilizing the chair conformation. In the solid state the molecules pack in an orientation consistent with electrostatic ordering. Our synthesis of this highest-energy isomer demonstrates the properties that accompany the placement of axial fluorines on a cyclohexane and the unusual property of a facially polarized ring in organic chemistry. Derivatives have potential as new motifs for the design of functional organic molecules or for applications in supramolecular chemistry design.

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Figure 1: Structures and relative energies of all isomers of 1,2,3,4,5,6-hexafluorocyclohexane.
Figure 2: Synthetic route to all-cis 1,2,3,4,5,6-hexafluorocyclohexane 1.
Figure 3: 19F{1H} NMR spectra of all-cis 1,2,3,4,5,6-hexafluorocyclohexane 1.
Figure 4: Different representations of all-cis 1,2,3,4,5,6-hexafluorocyclohexane 1.
Figure 5: Representation of the crystal packing structure of 1, derived from single-crystal X-ray data.
Figure 6: Representation of the two-dimensional structure of C2F chair graphene21.

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Acknowledgements

This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) and the European Research Council (ERC). D.O'H. thanks the Royal Society for a Wolfson Research Merit Award. The authors acknowledge the EPSRC National Mass Spectrometry Facility (Swansea) for analytical assistance.

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Authors

Contributions

N.K. and D.O'H conceived the synthesis of 1. N.K. designed the synthetic route and performed all of the synthesis and standard characterization. A.M.Z.S. obtained and solved the crystallographic data. T.L. conducted the low-temperature EXSY NMR studies and analysed the data. D.P. carried out the density functional theory and NBO theory studies. The manuscript was co-written by N.K. and D.O'H. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to David O'Hagan.

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The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 24174 kb)

Supplementary information

Crystallographic data for compound 1 (CIF 88 kb)

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Crystallographic data for compound 3 (CIF 268 kb)

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Crystallographic data for compound 5 (CIF 599 kb)

Supplementary information

Crystallographic data for compound 7 (CIF 128 kb)

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Crystallographic data for compound 8 (CIF 242 kb)

Supplementary information

GAMESS-US output for electronic structure calculation performed on Compound 1 at the M11/6-311G(2d,p) level of theory (TXT 2119 kb)

Supplementary information

NBO6 .47 archive file for Compound 1 (TXT 8640 kb)

Supplementary information

Output file from NBO analysis of Compound 1 (TXT 1854 kb)

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Keddie, N., Slawin, A., Lebl, T. et al. All-cis 1,2,3,4,5,6-hexafluorocyclohexane is a facially polarized cyclohexane. Nature Chem 7, 483–488 (2015). https://doi.org/10.1038/nchem.2232

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