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Kinetic resolution of constitutional isomers controlled by selective protection inside a supramolecular nanocapsule

Nature Chemistry volume 2, pages 847–852 (2010)Cite this article

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Abstract

The concept of self-assembling container molecules as yocto-litre reaction flasks is gaining prominence. However, the idea of using such containers as a means of protection is not well developed. Here, we illustrate this idea in the context of kinetic resolutions. Specifically, we report on the use of a water-soluble, deep-cavity cavitand to bring about kinetic resolutions within pairs of esters that otherwise cannot be resolved because they react at very similar rates. Resolution occurs because the presence of the cavitand leads to a competitive binding equilibrium in which the stronger binder primarily resides inside the host and the weaker binding ester primarily resides in the bulk hydrolytic medium. For the two families of ester examined, the observed kinetic resolutions were highest within the optimally fitting smaller esters.

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Figure 1: Molecular structures of the host and guests used in this study.
Figure 2: Binding of esters inside a deep-cavity cavitand.
Figure 3: Kinetics for the hydrolysis of ester 6 in the presence or absence of the cavitand.
Figure 4: Hydrolysis of similarly sized esters encapsulated within host 12.

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Acknowledgements

B.C.G. acknowledges financial support from the National Science Foundation (NSF; CHE-0718461), the National Institutes of Health (NIH; GM074031) and the Post-Katrina Support Fund Initiative (PKSFI, LEQSF(2007-12)-ENH-PKSFI-PRS-04). S.W.R. acknowledges financial support from the NSF (CHE-0611679). The authors also thank G. Raman and A. Sankaranarayanan for calculating the dipole, log P and solubility values of esters 2 to 6.

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Authors and Affiliations

  1. Department of Chemistry, University of New Orleans, New Orleans, 70148, Louisiana, USA

    Simin Liu, Haiying Gan, Andrew T. Hermann, Steven W. Rick & Bruce C. Gibb

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  1. Simin Liu
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Contributions

B.C.G. and S.L. conceived and designed the experiments. S.L. synthesized esters 2–6 and performed the experiments involving these guests. H.G. and A.T.H contributed equally to the syntheses and experiments involving esters 7–11. B.C.G. wrote the paper.

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Correspondence to Bruce C. Gibb.

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Liu, S., Gan, H., Hermann, A. et al. Kinetic resolution of constitutional isomers controlled by selective protection inside a supramolecular nanocapsule. Nature Chem 2, 847–852 (2010). https://doi.org/10.1038/nchem.751

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