Skip to content

Research at St Andrews

Polar organofluorine substituents: multivicinal fluorines on alkyl chains and alicyclic rings

Research output: Contribution to journalReview articlepeer-review


This review outlines the progression, primarily of our own work, but with important contributions from other labs, on the synthesis and properties of multiple vicinally fluorinated alkyl chains and rings. Chain conformations of individual diastereoisomers with –CHF‐ at adjacent carbons are influenced by stereoelectronic factors associated with the polar C‐F bond and the polarised geminal hydrogens. Generally the chain will prefer a conformation which acts to minimise overall molecular polarity, and where the C‐F bonds orient away from each other. However when vicinal fluorines are positioned on a ring then conformations are more constrained. The ring will adopt optimal conformations such as a chair in cyclohexane and then C‐F bonds can be introduced with a stereochemistry that forces parallel (axial) orientations. In the case of cyclohexane, 1,3‐diaxial arrangements of C‐F bonds impart considerable polarity to the ring, resulting in an electronegative ‘fluorine face’ and an electropositive ‘hydrogen face’. For all‐ syn 1,2,3,4,5,6‐hexafluorocyclohexane, this arrangement generates an unusually polar aliphatic ring system. Most recently the concept has been extended to the preparation of all‐ syn 1,2,3‐trifluorocyclopropanes, a rigid ring system with fluorines on one face and hydrogens on the other. Log Ps of such compounds indicate that they are significantly more polar than their parent alicyclic hydrocarbons and give some positive indication for a future role of such substituents in medicinal chemistry. Expanding to such a role will require access to improved synthesis methods to these motifs and consequently access to a broader a range of building blocks, however some exciting new methods have emerged recently and these are briefly reviewed.


Original languageEnglish
JournalChemistry - A European Journal
VolumeEarly View
Early online date8 May 2020
Publication statusE-pub ahead of print - 8 May 2020

    Research areas

  • Organofluorine chemistry, Selective fluorination, Aliphatic conformation, Alicyclic chemistry, Cyclopropanes

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Effect of fluoroalkyl-substituent in bistolane-based photoluminescence liquid crystals on their physical behavior

    Yamada, S., Wang, Y., Morita, M., Zhang, Q., O'Hagan, D., Nagata, M., Agou, T., Fukumoto, H., Kubota, T., Hara, M. & Konno, T., 20 Apr 2021, In: Crystals. 11, 4, 15 p., 450.

    Research output: Contribution to journalArticlepeer-review

  2. Organo-fluorine chemistry V

    O'Hagan, D., 17 Mar 2021, In: Beilstein Journal of Organic Chemistry. 17, p. 737-738

    Research output: Contribution to journalEditorial

  3. The contribution of non-classical CHax∙∙∙OC hydrogen bonds to the anomeric effect in fluoro and oxa-methoxycyclohexanes

    Piscelli, B., O'Hagan, D. & Cormanich, R., 2 Mar 2021, In: Physical Chemistry Chemical Physics. 23, 10, p. 5845-5851

    Research output: Contribution to journalArticlepeer-review

  4. Synthesis, radiosynthesis and in vitro studies on novel hypoxia PET tracers incorporating [18F]FDR

    Zanda, M., Musolino, M., Fleming, I. N., Schweiger, L. F., O’Hagan, D. & Dall’Angelo, S., 22 Feb 2021, In: European Journal of Organic Chemistry. Early View

    Research output: Contribution to journalArticlepeer-review

  5. Isolation of 5′-O-sulfamyladenosine and related 3′-O-β-glucosylated adenosines from the nucleocidin producer Streptomyces calvus

    Feng, X., Bello, D. & O'Hagan, D., 28 Jan 2021, In: RSC Advances. 11, 10, p. 5291-5294 4 p.

    Research output: Contribution to journalArticlepeer-review

Related by journal

  1. Chemistry - A European Journal (Journal)

    Stuart John Conway (Editor)

    2007 → …

    Activity: Publication peer-review and editorial work typesEditor of research journal

Related by journal

  1. Controlled synthesis of large single crystals of metal-organic framework CPO-27-Ni prepared by a modulation approach: in situ single crystal X-ray diffraction studies

    Vornholt, S. M., Elliott, C., Rice, C. M., Russell, S. E., Kerr, P. J., Rainer, D. N., Mazur, M., Warren, M. R., Wheatley, P. S. & Morris, R. E., 7 May 2021, In: Chemistry - A European Journal. Early View, 11 p.

    Research output: Contribution to journalArticlepeer-review

  2. Rapidly adaptive all-covalent nanoparticle surface engineering

    Diez-Castellnou, M., Suo, R., Marro, N., Matthew, S. & Kay, E. R., 14 Apr 2021, (Accepted/In press) In: Chemistry - A European Journal.

    Research output: Contribution to journalArticlepeer-review

  3. Synthesis of gold(I)-trifluoromethyl complexes and their role in generating spectroscopic evidence for a gold(I)-difluorocarbene species

    Nolan, S. P., Vanden Broeck, S. M. P., Nelson, D. J., Collado, A., Falivene, L., Cavallo, L., Cordes, D. B., Slawin, A. M. Z., Van Hecke, K., Nahra, F. & Cazin, C. S. J., 6 Apr 2021, (Accepted/In press) In: Chemistry - A European Journal. In press

    Research output: Contribution to journalArticlepeer-review

  4. A mechanistically and operationally simple route to metal-N-heterocyclic carbene (NHC) Complexes

    Nolan, S. P., Tzouras, N., Nahra, F., Falivene, L., Cavallo, L., Saab, M., Van Hecke, K., Collado, A., Collett, C., Smith, A. D. & Cazin, C. S. J., 12 Mar 2020, In: Chemistry - A European Journal. Early View

    Research output: Contribution to journalArticlepeer-review

  5. Catalytic enantioselective synthesis of heterocyclic vicinal fluoroamines using asymmetric protonation: a method development and mechanistic study

    Ashford, M., Xu, C., Molloy, J. J., Carpenter-Warren, C. L., Slawin, A. M. Z., Leach, A. G. & Watson, A. J. B., 21 Sep 2020, In: Chemistry - A European Journal. 26, 53, p. 12249-12255 8 p.

    Research output: Contribution to journalArticlepeer-review

ID: 266581891