Skip to content

Research at St Andrews

Fluorine in fragrances: exploring the difluoromethylene (CF2) group as a conformational constraint in macrocyclic musk lactones

Research output: Contribution to journalArticle

DOI

Open Access permissions

Open

Author(s)

Michael James Corr, Rodrigo Cormanich, Cortney von Hahmann, Michael Buehl, David Bradford Cordes, Alexandra Martha Zoya Slawin, David O'Hagan

School/Research organisations

Abstract

The CF2 group is incorporated into specific positions within the lactone ring of the natural musk lactone, (12R)-(+)-12-methyl-13-tridecanolide, a constituent of Angelica root oil, Angelica archangelica L. The approach is taken as it was anticipated that CF2 groups would dictate corner locations in the macrocycle and limit the conformational space available to the lactone. Three fluorine containing lactones are prepared by organic synthesis. One (8) has CF2 groups located at the C-6 and C-9 positions, another (9) with CF2 groups at the C-5 and C-9 positions, and a third (10) with a CF2 group at C-8. Two of the fluorine containing lactones (8 and 10) were sufficiently crystalline to obtain X-ray crystal structures which revealed that the CF2 groups do adopt corner locations. All three lactones were subject to computational analysis at the B3LYP-D3/6-311+G** level to assess the relative energies of different conformers. In all cases, the global minima and most of the lowest energy minima have squared /rectangular geometries and located the CF2 groups at the corners. The lowest energy structures for 8 and 10 closely approximated the observed X-ray structures, suggesting good convergence of theory and experiment in determining relevant low energy conformations. All three compounds retained a pleasant odour suggesting the rings retained sufficient conformational flexibility to access relevant olfactory conformations.

Close

Details

Original languageEnglish
Pages (from-to)211-219
JournalOrganic & Biomolecular Chemistry
Volume14
Issue number1
Early online date4 Nov 2015
DOIs
Publication statusPublished - 7 Jan 2016

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

View graph of relations

Related by author

  1. Probing the helical integrity of multivicinal all-syn-fluoro alkanes

    Al-Maharik, N., Cordes, D. B., Slawin, A. M. Z., Buhl, M. & O'Hagan, D., 7 Feb 2020, In : Organic & Biomolecular Chemistry. 18, 5, p. 878-887 10 p.

    Research output: Contribution to journalArticle

  2. Fluorinated cyclopropanes: Synthesis and chemistry of the aryl α,β,β-trifluorocyclopropane motif

    Thomson, C., Zhang, Q., Al-Maharik, N., Buehl, M., Cordes, D. B., Slawin, A. & O'Hagan, D., 3 Jul 2018, In : Chemical Communications. In press

    Research output: Contribution to journalArticle

  3. The synthesis and evaluation of fluoro-, trifluoromethyl, and iodomuscimols as GABA agonists

    Abdul Manan, M. A. F., Cordes, D., Slawin, A., Buehl, M., Liao, V., Chua, H., Chebib, M. & O'Hagan, D., 10 Aug 2017, In : Chemistry - A European Journal. 23, 45, p. 10848-10852 5 p.

    Research output: Contribution to journalArticle

  4. Unexpected α,α'-difluoroethers from Ag(i)F and N-bromosuccinimide reactions of dibenzo[a,e]cyclooctatetraene

    Fang, Z., Gillatt, R. Z., Slawin, A. M. Z., Cordes, D. B., Carpenter-Warren, C. L. & O'Hagan, D., 11 Dec 2019, In : Chemical Communications. 55, 95, p. 14295-14298 4 p.

    Research output: Contribution to journalArticle

Related by journal

  1. Organic & Biomolecular Chemistry (Journal)

    Stuart John Conway (Editor)
    2007 → …

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

Related by journal

  1. Probing the helical integrity of multivicinal all-syn-fluoro alkanes

    Al-Maharik, N., Cordes, D. B., Slawin, A. M. Z., Buhl, M. & O'Hagan, D., 7 Feb 2020, In : Organic & Biomolecular Chemistry. 18, 5, p. 878-887 10 p.

    Research output: Contribution to journalArticle

  2. An enzymatic Finkelstein reaction: fluorinase catalyses direct halogen exchange

    Lowe, P. T., Cobb, S. L. & O'Hagan, D., 28 Aug 2019, In : Organic & Biomolecular Chemistry. 17, 32, p. 7493-7496 4 p.

    Research output: Contribution to journalArticle

  3. Enzymatic radiosynthesis of a 18F-Glu-Ureido-Lys ligand for the prostate-specific membrane antigen (PSMA)

    Lowe, P. T., Dall'Angelo, S., Fleming, I. N., Piras, M., Zanda, M. & O'Hagan, D., 14 Feb 2019, In : Organic & Biomolecular Chemistry. 17, 6, p. 1480-1486 7 p.

    Research output: Contribution to journalArticle

  4. Evaluating aryl esters as bench-stable C(1)-ammonium enolate precursors in catalytic, enantioselective Michael addition-lactonisations

    Young, C. M., Taylor, J. E. & Smith, A. D., 21 May 2019, In : Organic & Biomolecular Chemistry. 17, 19, p. 4747-4752

    Research output: Contribution to journalArticle

ID: 228951170

Top