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Ultra-remote stereocontrol by conformational communication of information along a carbon chain

Nature volume 431, pages 966–971 (2004)Cite this article

Abstract

Many receptors1 and allosteric proteins2 function through binding of a molecule to induce a conformational change, which then influences a remote active site. In synthetic systems, comparable intramolecular information transfer can be effected by using the shape of one part of a molecule to control the stereoselectivity of reactions occurring some distance away3. However, the need for direct communication with the reaction site usually limits such remote stereocontrol to distances of not more than about five bond lengths. Cyclic structures overcome this problem by allowing the controlling centre and the reaction site4,5 to approach each other, but the information transfer spans only short absolute distances. Truly remote stereocontrol can, however, be achieved with rigid compounds containing amide groups: the conformation of the amides can be controlled by stereogenic centres6,7,8,9 and responds to that of neighbouring amide groups10,11,12 and in turn influences stereoselective reactions13. This strategy has allowed remote stereocontrol spanning 8 (ref. 11) or 9 (ref. 12) bonds. Here we demonstrate stereocontrol over a reaction taking place more than 20 bond lengths from the controlling centre, corresponding to a linear distance of over 2.5 nm. This transmission of information, achieved by conformational changes relayed through the molecule, provides a chemical model of allostery and might serve as a molecular mechanism for communicating and processing information14,15,16.

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Figure 1
Figure 2
Figure 3: Synthesis of bisxanthene 8.
Figure 4: Remote stereocontrol in a xanthene and a bisxanthene.
Figure 5: Inverting relative stereochemistry from a distance.
Figure 6: Ultra-remote stereocontrol in a trisxanthene.
Figure 7: Symmetry matching in bis-oxazolidines.

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Acknowledgements

We are grateful to the EPSRC for support of this work.

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Authors and Affiliations

  1. Department of Chemistry, University of Manchester, Oxford Road, M13 9PL, Manchester, UK

    Jonathan Clayden, Andrew Lund, Lluís Vallverdú & Madeleine Helliwell

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  1. Jonathan Clayden
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  2. Andrew Lund
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  3. Lluís Vallverdú
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  4. Madeleine Helliwell
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Correspondence to Jonathan Clayden.

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The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Information

Contains: Supplementary Figures S1-S6, showing NMR and HPLC evidence for the level of remote stereocontrol achieved in the addition reactions, Supplementary Figures S7-S8, showing X-ray crystal structures of 9 and 20, and experimental procedures and characterisation data for new compounds reported. (PDF 598 kb)

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Clayden, J., Lund, A., Vallverdú, L. et al. Ultra-remote stereocontrol by conformational communication of information along a carbon chain. Nature 431, 966–971 (2004). https://doi.org/10.1038/nature02933

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