Catalytic enantioselective syn hydration of enones in water using a DNA-based catalyst

Abstract

The enantioselective addition of water to olefins in an aqueous environment is a common transformation in biological systems, but was beyond the ability of synthetic chemists. Here, we present the first examples of a non-enzymatic catalytic enantioselective hydration of enones, for which we used a catalyst that comprises a copper complex, based on an achiral ligand, non-covalently bound to (deoxy)ribonucleic acid, which is the only source of chirality present under the reaction conditions. The chiral β-hydroxy ketone product was obtained in up to 82% enantiomeric excess. Deuterium-labelling studies demonstrated that the reaction is diastereospecific, with only the syn hydration product formed. So far, this diastereospecific and enantioselective reaction had no equivalent in conventional homogeneous catalysis.

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Figure 1: Enantioselective hydration of α,β-unsaturated ketones.
Figure 2: Temporal evolution of enantiomeric excess and conversion.
Figure 3: Diastereospecificity of the catalytic hydration reaction.

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Acknowledgements

This work was supported by grants from the National Research School Combination – Catalysis, the European Research Area Chemistry program and the Netherlands Organisation for Scientific Research.

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A.J.B., B.L.F. and G.R. conceived the project; A.J.B., D.C. and G.R. designed the experiments; A.J.B., D.C., D.G. and F.R. performed the experiments and analysed the data. A.J.B., B.L.F. and G.R. co-wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Ben L. Feringa or Gerard Roelfes.

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The authors declare no competing financial interests.

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Boersma, A., Coquière, D., Geerdink, D. et al. Catalytic enantioselective syn hydration of enones in water using a DNA-based catalyst. Nature Chem 2, 991–995 (2010). https://doi.org/10.1038/nchem.819

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