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Conformer-specific hydrogen atom tunnelling in trifluoromethylhydroxycarbene

Nature Chemistry volume 9, pages 71–76 (2017)Cite this article

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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.

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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.

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Acknowledgements

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

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Authors and Affiliations

  1. Institute of Organic Chemistry, Justus-Liebig University, Heinrich-Buff-Ring 17, Giessen, 35392, Germany

    Artur Mardyukov, Henrik Quanz & Peter R. Schreiner

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  1. Artur Mardyukov
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  3. Peter R. Schreiner
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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.

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Correspondence to Peter R. Schreiner.

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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

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