An enantiomerically pure hydrogen-bonded assembly

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Abstract

Chiral molecules have asymmetric arrangements of atoms, forming structures that are non-superposable mirror images of each other. Specific mirror images (‘enantiomers’) may be obtained either from enantiomerically pure precursor compounds, through enantioselective synthesis, or by resolution of so-called racemic mixtures of opposite enantiomers, provided that racemization (the spontaneous interconversion of enantiomers) is sufficiently slow. Non-covalent assemblies can similarly adopt chiral supramolecular structures1,2, and if they are held together by relatively strong interactions, such as metal coordination3, methods analogous to those used to obtain chiral molecules yield enantiomerically pure non-covalent products. But the resolution of assemblies formed through weak interactions, such as hydrogen-bonding, remains challenging, reflecting their lower stability and significantly higher susceptibility to racemization. Here we report the design of supramolecular structures from achiral calix[4]arene dimelamines and cyanurates, which form multiple cooperative hydrogen bonds that together provide sufficient stability to allow the isolation of enantiomerically pure assemblies. Our design strategy is based on a non-covalent ‘chiral memory’ concept4,5, whereby we first use chiral barbiturates to induce the supramolecular chirality in a hydrogen-bonded assembly6, and then substitute them by achiral cyanurates. The stability of the resultant chiral assemblies in benzene, a non-polar solvent not competing for hydrogen bonds, is manifested by a half-life to racemization of more than four days at room temperature.

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Figure 1: Formation of non-covalent chiral assemblies with typical composition 13·(BAR)6 and 13·(CYA)6.
Figure 2
Figure 3: Non-covalent synthesis of an enantiomerically pure hydrogen-bonded assembly.
Figure 4: Study of the racemization process by circular dichroism.
Figure 5: Schematic representations of the different racemization pathways.

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Acknowledgements

We thank C. Marjo and A. Bielejewska for their work on the model complexes 4·5 and 4·6, and R. Fokkens and N.M.M. Nibbering for the MALDI-TOF MS measurements. This work was supported by the Council for Chemical Sciences of the Netherlands Organization for Scientific Research (CW-NWO).

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Correspondence to David N. Reinhoudt.

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