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Computational evidence that hyperconjugative interactions are not responsible for the anomeric effect

Nature Chemistry volume 2, pages 666–671 (2010)Cite this article

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A Corrigendum to this article was published on 01 September 2010

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Abstract

The ‘anomeric effect’ is the thermodynamic preference for polar substituents to occupy the axial position in the chair conformation of various heterocycles. The most common explanation given for this effect at present is hyperconjugation from the lone pairs on the ring heteroatom to the antibonding orbital between the anomeric carbon and its linking substituent. Alternatively, the anomeric effect could be explained by intramolecular electrostatic interactions between local dipoles. Few models can provide convincing data for either theory at the quantum-mechanical level. Now, using the extended block-localized wavefunction method, which is the simplest form of valence bond theory, we have evaluated the degree of hyperconjugation in various compounds that display the anomeric effect and have interpreted their conformational preferences in terms of steric, hyperconjugation and dispersion effects. The results provide strong evidence that hyperconjugative interactions are not responsible for the anomeric effect and that it is better interpreted in terms of electrostatic interactions.

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Figure 1: Anomeric effect in substituted tetrahydropyran.
Figure 2: Two most common explanations for the anomeric effect.
Figure 3: Electron density difference (EDD) maps showing electron delocalization within compounds displaying the anomeric effect.

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Change history

  • 28 July 2010

    In the version of this Article originally published, Fig. 1 was incorrect. This error has now been corrected in the HTML and PDF versions of the Article.

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Acknowledgements

This work was supported by the Keck Foundation and Western Michigan University.

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  1. Department of Chemistry, Western Michigan University, Kalamazoo, 49008, Michigan, USA

    Yirong Mo

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Mo, Y. Computational evidence that hyperconjugative interactions are not responsible for the anomeric effect. Nature Chem 2, 666–671 (2010). https://doi.org/10.1038/nchem.721

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