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.

Conformer-specific hydrogen atom tunnelling in trifluoromethylhydroxycarbene

Abstract

Conformational control of organic reactions is at the heart of the biomolecular sciences. To achieve a particular reactivity, one of many conformers may be selected, for instance, by a (bio)catalyst, as the geometrically most suited and appropriately reactive species. The equilibration of energetically close-lying conformers is typically assumed to be facile and less energetically taxing than the reaction under consideration itself: this is termed the ‘Curtin–Hammett principle’. Here, we show that the trans conformer of trifluoromethylhydroxycarbene preferentially rearranges through a facile quantum-mechanical hydrogen tunnelling pathway, while its cis conformer is entirely unreactive. Hence, this presents the first example of a conformer-specific hydrogen tunnelling reaction. The Curtin–Hammett principle is not applicable, due to the high barrier between the two conformers.

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

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Schematic presentation of the thermal generation of trans-trifluoromethylhydroxycarbene (1t) from 3,3,3-trifluoro-2-oxopropanoic acid (3) and subsequent reactions.
Figure 2: Comparison of experimentally measured and computed infrared spectra for the key compounds in the observed tunnelling isomerization.
Figure 3: Depiction of the computed potential energy surface (ΔH0) of ground-state singlet 1t for its unimolecular reactions at CCSD(T)/cc-pVTZ.
Figure 4: Time evolution of a selection of infrared bands for the disappearance of 1t.
Figure 5: Comparison of the intrinsic reaction coordinates of 1t and 8t for rearrangement to their corresponding aldehydes.

References

  1. Assion, A. et al. Control of chemical reactions by feedback-optimized phase-shaped femtosecond laser pulses. Science 282, 919–922 (1998).

    Article  CAS  Google Scholar 

  2. Kim, M. H., Shen, L., Tao, H., Martinez, T. J. & Suits, A. G. Conformationally controlled chemistry: excited-state dynamics dictate ground-state reaction. Science 315, 1561–1565 (2007).

    Article  CAS  Google Scholar 

  3. Choi, K.-W., Ahn, D.-S., Lee, J.-H. & Kim, S. K. A highly conformationally specific α- and β-Ala+ decarboxylation pathway. Chem. Commun. 1041–1043 (2007).

  4. Zuev, P. S., Sheridan, R. S., Sauers, R. R., Moss, R. A. & Chu, G. Conformational product control in the low-temperature photochemistry of cyclopropylcarbenes. Org. Lett. 8, 4963–4966 (2006).

    Article  CAS  Google Scholar 

  5. Khriachtchev, L. et al. Conformation-dependent chemical reaction of formic acid with an oxygen atom. J. Phys. Chem. A 113, 8143–8146 (2009).

    Article  CAS  Google Scholar 

  6. Park, S. T., Kim, S. K. & Kim, M. S. Observation of conformation-specific pathways in the photodissociation of 1-iodopropane ions. Nature 415, 306–308 (2002).

    Article  Google Scholar 

  7. Khriachtchev, L., Pettersson, M. & Räsänen, M. Conformational memory in photodissociation of formic acid. J. Am. Chem. Soc. 124, 10994–10995 (2002).

    Article  CAS  Google Scholar 

  8. Ley, D., Gerbig, D. & Schreiner, P. R. Tunnelling control of chemical reactions—the organic chemist's perspective. Org. Biomol. Chem. 10, 3781–3790 (2012).

    Article  CAS  Google Scholar 

  9. Kästner, J. Theory and simulation of atom tunneling in chemical reactions. WIREs Comput. Mol. Sci. 4, 158–168 (2014).

    Article  Google Scholar 

  10. Borden, W. T. Reactions that involve tunneling by carbon and the role that calculations have played in their study. WIREs Comput. Mol. Sci. 6, 20–46 (2016).

    Article  CAS  Google Scholar 

  11. Kohen, A., Cannio, R., Bartolucci, S. & Klinman, J. P. Enzyme dynamics and hydrogen tunnelling in a thermophilic alcohol dehydrogenase. Nature 399, 496–499 (1999).

    Article  CAS  Google Scholar 

  12. Masgrau, L. et al. Atomic description of an enzyme reaction dominated by proton tunneling. Science 312, 237–241 (2006).

    Article  CAS  Google Scholar 

  13. Layfield, J. P. & Hammes-Schiffer, S. Hydrogen tunneling in enzymes and biomimetic models. Chem. Rev. 114, 3466–3494 (2014).

    Article  CAS  Google Scholar 

  14. Zuev, P. S. et al. Carbon tunneling from a single quantum state. Science 299, 867–870 (2003).

    Article  CAS  Google Scholar 

  15. Schreiner, P. R. et al. Methylhydroxycarbene: tunneling control of a chemical reaction. Science 332, 1300–1303 (2011).

    Article  CAS  Google Scholar 

  16. Ley, D., Gerbig, D., Wagner, J. P., Reisenauer, H. P. & Schreiner, P. R. Cyclopropylhydroxycarbene. J. Am. Chem. Soc. 133, 13614–13621 (2011).

    Article  CAS  Google Scholar 

  17. Schreiner, P. R. et al. Capture of hydroxymethylene and its fast disappearance through tunnelling. Nature 453, 906–909 (2008).

    Article  CAS  Google Scholar 

  18. Krueger, P. J. & Mettee, H. D. Spectroscopic studies of alcohols III. Fundamental OH stretching bands of 2,2-di- and 2,2,2-tri-haloethanols. Can. J. Chem. 42, 340–346 (1964).

    Article  CAS  Google Scholar 

  19. Glendening, E. D., Landis, C. R. & Weinhold, F. Natural bond orbital methods. WIREs Comput. Mol. Sci. 2, 1–42 (2012).

    Article  CAS  Google Scholar 

  20. Bader, R. F. W. Atoms in molecules. Acc. Chem. Res. 18, 9–15 (1985).

    Article  CAS  Google Scholar 

  21. Barbarich, T. J., Rithner, C. D., Miller, S. M., Anderson, O. P. & Strauss, S. H. Significant inter- and intramolecular O−H···F−C hydrogen bonding. J. Am. Chem. Soc. 121, 4280–4281 (1999).

    Article  CAS  Google Scholar 

  22. Razavy, M. Quantum Theory of Tunneling (World Scientific, 2003).

    Book  Google Scholar 

  23. Ley, D., Gerbig, D. & Schreiner, P. R. Tunneling control of chemical reactions: C–H insertion versus H-tunneling in tert-butylhydroxycarbene. Chem. Sci. 4, 677–684 (2013).

    Article  CAS  Google Scholar 

  24. Kästner, J. Path length determines the tunneling decay of substituted carbenes. Chem. Eur. J. 19, 8207–8212 (2013).

    Article  Google Scholar 

  25. Seeman, J. I. Effect of conformational change on reactivity in organic chemistry. Evaluations, applications, and extensions of Curtin–Hammett/Winstein–Holness kinetics. Chem. Rev. 83, 83–134 (1983).

    Article  CAS  Google Scholar 

  26. Oki, M. Reactivity of conformational isomers. Acc. Chem. Res. 17, 154–159 (1984).

    Article  CAS  Google Scholar 

  27. Amiri, S., Reisenauer, H. P. & Schreiner, P. R. Electronic effects on atom tunneling: conformational isomerization of monomeric para-substituted benzoic acid derivatives. J. Am. Chem. Soc. 132, 15902–15904 (2010).

    Article  CAS  Google Scholar 

  28. Pettersson, M., Maçôas, E. M. S., Khriachtchev, L., Fausto, R. & Räsänen, M. Conformational isomerization of formic acid by vibrational excitation at energies below the torsional barrier. J. Am. Chem. Soc. 125, 4058–4059 (2003).

    Article  CAS  Google Scholar 

  29. Reva, I., Nunes, C. M., Biczysko, M. & Fausto, R. Conformational switching in pyruvic acid isolated in Ar and N2 matrixes: spectroscopic analysis, anharmonic simulation, and tunneling. J. Phys. Chem. A 119, 2614–2627 (2015).

    Article  CAS  Google Scholar 

  30. Schreiner, P. R. et al. Domino tunneling. J. Am. Chem. Soc. 137, 7828–7834 (2015).

    Article  CAS  Google Scholar 

  31. Halasa, A. et al. Three conformers of 2-furoic acid: structure changes induced with near-IR laser light. J. Am. Chem. Soc. 119, 1037–1047 (2015).

    CAS  Google Scholar 

  32. Domanskaya, A., Marushkevich, K., Khriachtchev, L. & Räsänen, M. Spectroscopic study of cis-to-trans tunneling reaction of HCOOD in rare gas matrices. J. Chem. Phys. 130, 154509 (2009).

    Article  Google Scholar 

  33. Mackenzie, R. B., Dewberry, C. T. & Leopold, K. R. The formic acid–nitric acid complex: microwave spectrum, structure, and proton transfer. J. Phys. Chem. A 118, 7975–7985 (2014).

    Article  CAS  Google Scholar 

  34. Tsuge, M. & Khriachtchev, L. Tunneling isomerization of small carboxylic acids and their complexes in solid matrixes: a computational insight. J. Chem. Phys. A 119, 2628–2635 (2015).

    Article  CAS  Google Scholar 

  35. Maçôas, E. M. S., Khriachtchev, L., Pettersson, M., Fausto, R. & Räsänen, M. Rotational isomerism of acetic acid isolated in rare-gas matrices: effect of medium and isotopic substitution on IR-induced isomerization quantum yield and cistrans tunneling rate. J. Chem. Phys. 121, 1331–1338 (2004).

    Article  Google Scholar 

  36. Maçôas, E. M. S. et al. Infrared-induced conformational interconversion in carboxylic acids isolated in low-temperature rare-gas matrices. Vib. Spectrosc. 34, 73–82 (2004).

    Article  Google Scholar 

  37. Pettersson, M. et al. Cistrans conversion of formic acid by dissipative tunneling in solid rare gases: influence of environment on the tunneling rate. J. Chem. Phys. 117, 9095–9098 (2002).

    Article  CAS  Google Scholar 

  38. Bazsó, G., Góbi, S. & Tarczay, G. Near-infrared radiation induced conformational change and hydrogen atom tunneling of 2-chloropropionic acid in low-temperature Ar matrix. J. Phys. Chem. A 116, 4823–4832 (2012).

    Article  Google Scholar 

  39. Bazsó, G., Magyarfalvi, G. & Tarczay, G. Tunneling lifetime of the ttc/VIp conformer of glycine in low-temperature matrices. J. Phys. Chem. A 116, 10539–10547 (2012).

    Article  Google Scholar 

  40. Bazsó, G., Najbauer, E. E., Magyarfalvi, G. & Tarczay, G. Near-infrared laser induced conformational change of alanine in low-temperature matrixes and the tunneling lifetime of its conformer VI. J. Phys. Chem. A 117, 1952–1962 (2013).

    Article  Google Scholar 

  41. Gerbig, D. & Schreiner, P. R. Hydrogen-tunneling in biologically relevant small molecules: the rotamerizations of α-ketocarboxylic acids. J. Phys. Chem. B 119, 693–703 (2015).

    Article  CAS  Google Scholar 

  42. Alabugin, I. V., Gilmore, K. M. & Peterson, P. W. Hyperconjugation. WIREs Comput. Mol. Sci. 1, 109–141 (2011).

    Article  CAS  Google Scholar 

  43. Lopes, S., Domanskaya, A. V., Fausto, R., Räsänen, M. & Khriachtchev, L. Formic and acetic acids in a nitrogen matrix: enhanced stability of the higher-energy conformer. J. Chem. Phys. 133, 144507 (2010).

    Article  Google Scholar 

  44. Marushkevich, K., Khriachtchev, L., Lundell, J., Domanskaya, A. & Räsänen, M. Matrix isolation and ab initio study of Trans–Trans and Trans–Cis dimers of formic acid. J. Chem. Phys. A 114, 3495–3502 (2010).

    Article  CAS  Google Scholar 

  45. Marushkevich, K., Khriachtchev, L., Lundell, J. & Räsänen, M. cis–trans formic acid dimer: experimental observation and improved stability against proton tunneling. J. Am. Chem. Soc. 128, 12060–12061 (2006).

    Article  CAS  Google Scholar 

  46. Marushkevich, K., Khriachtchev, L. & Räsänen, M. Hydrogen bonding between formic acid and water: complete stabilization of the intrinsically unstable conformer. J. Phys. Chem. A 111, 2040–2042 (2007).

    Article  CAS  Google Scholar 

  47. Marushkevich, K., Khriachtchev, L. & Räsänen, M. High-energy conformer of formic acid in solid neon: giant difference between the proton tunneling rates of cis monomer and trans–cis dimer. J. Chem. Phys. 126, 241102 (2007).

    Article  Google Scholar 

  48. Marushkevich, K., Räsänen, M. & Khriachtchev, L. Interaction of formic acid with nitrogen: stabilization of the higher-energy conformer. J. Phys. Chem. A 114, 10584–10589 (2010).

    Article  CAS  Google Scholar 

  49. Tsuge, M., Marushkevich, K., Räsänen, M. & Khriachtchev, L. Infrared characterization of the HCOOH···CO2 complexes in solid argon: stabilization of the higher-energy conformer of formic acid. J. Phys. Chem. A 116, 5305–5311 (2012).

    Article  CAS  Google Scholar 

  50. Pettersson, M., Lundell, J., Khriachtchev, L. & Räsänen, M. IR spectrum of the other rotamer of formic acid, cis-HCOOH. J. Am. Chem. Soc. 119, 11715–11716 (1997).

    Article  CAS  Google Scholar 

  51. Marushkevich, K., Khriachtchev, L. & Räsänen, M. High-energy conformer of formic acid in solid hydrogen: conformational change promoted by host excitation. Phys. Chem. Chem. Phys. 9, 5748–5751 (2007).

    Article  CAS  Google Scholar 

  52. CFOUR (Coupled-Cluster Techniques for Computational Chemistry) quantum chemical program package www.cfour.de/.

  53. Gaussian09, Revision B.02 (Gaussian, 2009).

Download references

Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft. The authors thank I. Alabugin and G. dos Passos Gomes (FSU Tallahassee) for discussions.

Author information

Authors and Affiliations

Authors

Contributions

A.M. and P.R.S. conceived the experiments. A.M. performed the experiments and all data analysis. A.M. and H.Q. carried out all computations. All authors co-wrote the manuscript.

Corresponding author

Correspondence to Peter R. Schreiner.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 2750 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mardyukov, A., Quanz, H. & Schreiner, P. Conformer-specific hydrogen atom tunnelling in trifluoromethylhydroxycarbene. Nature Chem 9, 71–76 (2017). https://doi.org/10.1038/nchem.2609

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.2609

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