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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This work was supported by the Deutsche Forschungsgemeinschaft. The authors thank I. Alabugin and G. dos Passos Gomes (FSU Tallahassee) for discussions.
The authors declare no competing financial interests.
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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