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Dynamic multi-component covalent assembly for the reversible binding of secondary alcohols and chirality sensing

Nature Chemistry volume 3, pages 943–948 (2011)Cite this article

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Abstract

Reversible covalent bonding is often used for the creation of novel supramolecular structures, multi-component assemblies and sensing ensembles. Despite the remarkable success of dynamic covalent systems, the reversible binding of a mono-alcohol with high strength is challenging. Here, we show that a strategy of carbonyl activation and hemiaminal ether stabilization can be embodied in a four-component reversible assembly that creates a tetradentate ligand and incorporates secondary alcohols with exceptionally high affinity. Evidence is presented that the intermediate leading to binding and exchange of alcohols is an iminium ion. To demonstrate the use of this assembly process we also explored chirality sensing and enantiomeric excess determinations. An induced twist in the ligand by a chiral mono-ol results in large Cotton effects in the circular dichroism spectra indicative of the handedness of the alcohol. The strategy revealed in this study should prove broadly applicable for the incorporation of alcohols into supramolecular architecture construction.

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Figure 1: Proposed solution to the challenge of the binding of secondary alcohols.
Figure 2: Component exchange within the multi-component assembly.
Figure 3: Experimental evidence and proposed mechanism for multi-component assembly.
Figure 4: Exploration of four-component assembly for chirality sensing and e.e. determination.

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Acknowledgements

The authors thank B. Shoulders and S. Sorey for NMR assistance, K. Keller for mass spectrometric assistance and E.J. Cho of the Texas Institute for Drug and Diagnostic Development. The authors are grateful for the financial support provided by the National Institutes of Health (GM 077437) and the Welch Foundation (F-1151).

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, 78712, Texas, USA

    Lei You, Jeffrey S. Berman & Eric V. Anslyn

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  1. Lei You
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Contributions

L.Y. and E.V.A. developed the strategy and the mechanistic concepts. L.Y. performed the experiments. J.S.B. participated in the reaction optimization. E.V.A. directed the research. L.Y. and E.V.A. wrote the manuscript.

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Correspondence to Eric V. Anslyn.

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The authors declare no competing financial interests.

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You, L., Berman, J. & Anslyn, E. Dynamic multi-component covalent assembly for the reversible binding of secondary alcohols and chirality sensing. Nature Chem 3, 943–948 (2011). https://doi.org/10.1038/nchem.1198

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