Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Absolute configuration of chirally deuterated neopentane

Nature volume 446, pages 526–529 (2007)Cite this article

Abstract

The relationship between macroscopic chirality and chirality on the molecular level was unequivocally established in 1951 through anomalous X-ray scattering1. Although this technique became the definitive method for determining the absolute configuration of a molecule, one important limitation of the approach is that the molecule must contain ‘heavy’ atoms (for example, bromine). The direct determination of absolute configurations for a wider range of molecules has recently become possible by measuring a molecule’s vibrational optical activity2,3. Here we show that instrumental advances in Raman optical activity4,5, combined with quantum chemical computations6,7,8, make it possible to determine the absolute configuration of (R)-[2H1, 2H2, 2H3]-neopentane9. This saturated hydrocarbon represents the archetype of all molecules that are chiral as a result of a dissymmetric mass distribution. It is chemically inert and cannot be derivatized to yield molecules that would reveal the absolute configuration of the parent compound. Diastereomeric interactions with other molecules, optical rotation, and electronic circular dichroism are, in contrast to the well-known case of bromochlorofluoromethane10,11,12, not expected to be measurable. Vibronic effects in the vacuum ultraviolet circular dichroism might reveal that the molecule is chiral, but the presence of nine rotamers would make it extremely difficult to interpret the spectra, because the spatial arrangement of the rotamers’ nuclei resembles that of enantiomers. The unequivocal spectroscopic determination of the absolute configuration of (R)-[2H1, 2H2, 2H3]-neopentane therefore presented a major challenge, one that was at the very limit of what is possible.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Synthetic route to chirally deuterated neopentane 1.
Figure 2: 13 C-NMR characterization of the quaternary centre.
Figure 3: ROA spectra of ( R)-[2H1, 2H2, 2H3]-neopentane.
Figure 4: Raman spectra of ( R)-[2H1, 2H2, 2H3]-neopentane.

References

  1. Bijvoet, J. M., Peerdeman, A. F. & van Bommel, A. J. Determination of the absolute configuration of optically active compounds by means of X-rays. Nature 168, 271–272 (1951)

    Article  ADS  CAS  Google Scholar 

  2. Barron, L. D., Bogaard, M. P. & Buckingham, A. D. Raman scattering of circularly polarized light by optically active molecules. J. Am. Chem. Soc. 95, 603–605 (1973)

    Article  CAS  Google Scholar 

  3. Holzwarth, G., Hsu, E. C., Mosher, H. S., Faulkaner, T. R. & Moscowitz, A. Infrared circular dichroism of carbon-hydrogen and carbon-deuterium stretching modes. Observations. J. Am. Chem. Soc. 96, 251–252 (1974)

    Article  CAS  Google Scholar 

  4. Hug, W. & Hangartner, G. A novel high-throughput Raman spectrometer for polarization difference measurements. J. Raman Spectrosc. 30, 841–852 (1999)

    Article  ADS  CAS  Google Scholar 

  5. Hug, W. Virtual enantiomers as the solution of optical activity's deterministic offset problem. Appl. Spectrosc. 57, 1–13 (2003)

    Article  ADS  CAS  Google Scholar 

  6. Helgaker, T., Ruud, K., Bak, K. L., Joergensen, P. & Olsen, J. Vibrational Raman optical activity calculations using London atomic orbitals. Faraday Discuss. 99, 165–180 (1994)

    Article  ADS  CAS  Google Scholar 

  7. Ruud, K., Helgaker, T. & Bouř, P. Gauge-origin independent density-functional theory calculations of vibrational Raman optical activity. J. Phys. Chem. A 106, 7448–7455 (2002)

    Article  CAS  Google Scholar 

  8. Zuber, G. & Hug, W. Rarefied basis sets for the calculation of optical tensors. 1. The importance of gradients on hydrogen atoms for the Raman scattering tensor. J. Phys. Chem. 108, 2108–2118 (2004)

    Article  CAS  Google Scholar 

  9. Hug, W. & Haesler, J. Is the vibrational optical activity of (R)-[2H1, 2H2, 2H3]-neopentane measurable? Int. J. Quantum Chem. 104, 695–715 (2005)

    Article  ADS  CAS  Google Scholar 

  10. Costante, J., Hecht, L., Polavarapu, P. L., Collet, A. & Barron, L. D. Absolute configuration of bromochlorofluoromethane from experimental and ab initio theoretical vibrational Raman optical activity. Angew. Chem. Int. Edn Engl. 36, 885–887 (1997)

    Article  CAS  Google Scholar 

  11. Crassous, J. & Collet, A. The bromochlorofluoromethane saga. Enantiomer 5, 429–438 (2000)

    CAS  PubMed  Google Scholar 

  12. Jiang, Z., Crassous, J. & Schurig, V. Gas-chromatographic separation of tri(hetero)halogenomethane enantiomers. Chirality 17, 488–493 (2005)

    Article  CAS  Google Scholar 

  13. Abe, T., Suzuki, T., Sekiguchi, K., Hosokawa, S. & Kobayashi, S. Stereoselective construction of a quaternary carbon substituted with multifunctional groups: application to the concise synthesis of (+)-ethosuximide. Tetrahedr. Lett. 44, 9303–9305 (2003)

    Article  CAS  Google Scholar 

  14. Barron, L. D. Molecular Light Scattering and Optical Activity 162, Ch. 3 (Cambridge Univ. Press, Cambridge, 2004)

    Book  Google Scholar 

  15. Long, D. A. Raman Spectroscopy 130 (McGraw-Hill, New York, 1977)

    Google Scholar 

  16. Haesler, J. Construction of a New Forward and Backward Scattering Raman Optical Activity Spectrometer and Graphical Analysis of Measured and Calculated Spectra for (R)-[2H1, 2H2, 2H3]-neopentane. PhD thesis (Univ. Fribourg, 2006)

  17. Pitzer, K. S. & Kilpatrick, J. E. The entropies and related properties of branched paraffin hydrocarbons. Chem. Rev. 39, 435–447 (1946)

    Article  CAS  Google Scholar 

  18. Weiss, S. & Leroi, G. E. Infrared spectra and internal rotation in propane, isobutane, and neopentane. Spectrochim. Acta A 25, 1759–1766 (1969)

    Article  ADS  CAS  Google Scholar 

  19. Durig, J. R., Craven, S. M. & Bragin, J. Low-frequency modes in molecular crystals. VI. Methyl torsions and barriers to internal rotation of C(CH3)4, C(CD3)4, Si(CH3)4, Ge(CH3)4, and Sn(CH3)4 . J. Chem. Phys. 52, 2046–2052 (1970)

    Article  ADS  CAS  Google Scholar 

  20. Rush, J. J. Cold-neutron study of hindered rotations in solid and liquid methylchloroform, neopentane, and ethane. J. Chem. Phys. 46, 2285–2291 (1967)

    Article  ADS  CAS  Google Scholar 

  21. Grant, D. M., Strong, K. A. & Brugger, R. M. Direct observation of methyl librations in neopentane. Phys. Rev. Lett. 20, 983–986 (1968)

    Article  ADS  CAS  Google Scholar 

  22. Petryk, M. W. P. & Henry, B. R. Through space coupling and fermi resonances in neopentane-d0, -d6, -d9, and tetramethylsilane. J. Phys. Chem. 106, 8599–8608 (2002)

    Article  CAS  Google Scholar 

  23. Palmo, K., Mirkin, N. G. & Krimm, S. Spectroscopically determined force fields for macromolecules. 2. Saturated hydrocarbon chains. J. Phys. Chem. A 102, 6448–6456 (1998)

    Article  CAS  Google Scholar 

  24. Barth, G. & Djerassi, C. Circular dichroism of molecules with isotopically engendered chirality. Tetrahedron 37, 4123–4142 (1981)

    Article  CAS  Google Scholar 

  25. Barron, L. D. Raman optical activity due to isotopic substitution: [α-2H]benzyl alcohol. J. Chem. Soc. Chem. Commun. 9, 305–306 (1977)

    Article  Google Scholar 

  26. Hug, W. Instrumental and theoretical advances in Raman optical activity. In Raman Spectroscopy, Linear and Nonlinear (eds Lascombe, J. & Huong, P. V.) 3 (John Wiley & Sons, Chichester, 1982)

    Google Scholar 

  27. Polavarapu, P. L., Nafie, L. A., Benner, S. A. & Morton, T. H. Optical activity due to isotopic substitution. Vibrational circular dichroism and the absolute configurations of α-deuterated cyclohexanones. J. Am. Chem. Soc. 103, 5349–5359 (1981)

    Article  CAS  Google Scholar 

  28. Frisch, M. J. et al. Gaussian 03 Revision C.02 (Gaussian Inc., Wallingford, Connecticut, 2004)

    Google Scholar 

Download references

Acknowledgements

We thank F. Nydegger and F. Fehr for their analytical work. This work was supported by the Swiss National Science Foundation.

Author Contributions W.H. developed the design of the instrument. J.H. constructed the spectrometer used in this work and performed the ROA measurements. J.H. and I.S. isolated the sample in the capillary. J.H. performed the ab initio calculations. I.S. and E.R. performed and optimized the synthesis. C.G.B. designed the synthetic route. W.H. proposed this work. W.H. and C.G.B. wrote the paper. All authors discussed the results and commented on the manuscript.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Fribourg, ch. du Musée 9, CH-1700 Fribourg, Switzerland,

    J. Haesler, I. Schindelholz, E. Riguet, C. G. Bochet & W. Hug

Authors
  1. J. Haesler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Schindelholz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Riguet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. G. Bochet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W. Hug
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to J. Haesler or W. Hug.

Ethics declarations

Competing interests

Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures S1-S8 with Legends. Supplementary Figure S1 is a summary of the main findings. Supplementary Figure S2 shows the ratio Δ of ROA to Raman backscattering of (R)-[2H1, 2H2, 2H3]-neopentane and the degree of circularity. Supplementary Figure S3 shows an overview of the ROA spectrometer used in this work. This file also contains Supplementary Scheme S1 and Supplementary S2. Scheme S1 shows the intuitive conventional retrosynthetic analysis and Scheme S2 shows the synthetic route to chirally deuterated Neopentane. Finally, this file contains the synthetic protocols for all the intermediates and the detailed spectral data (1H-NMR, 13C-NMR, DEPT 135, 2H-NMR and MS-EI) for the characterization of (R)-[2H1, 2H2, 2H3]-neopentane (Figures S4-S8). (PDF 2760 kb)

Supplementary Data 1

This file contains Supplementary Data 1 with the spectral data for (4S)-Tiglyloxazolidinone 4, Oxazolidinone 5 and Alcohol 6. (PDF 3903 kb)

Supplementary Data 2

This file contains Supplementary Data 2 with the spectral data for Diol 7, Dimesylate 8 and Neopentane 1. (PDF 3098 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Haesler, J., Schindelholz, I., Riguet, E. et al. Absolute configuration of chirally deuterated neopentane. Nature 446, 526–529 (2007). https://doi.org/10.1038/nature05653

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature05653

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing