Skip to main content
SpringerLink
Log in

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

  • Article
  • Published:

From Nature Chemistry

View current issue Submit your manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

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.

Similar content being viewed by others

References

  1. Silverman, R. B. The Organic Chemistry of Enzyme Catalyzed Reactions Ch. 10 (Academic Press, 2000).

  2. Tokunaga, M., Larrow, J. F., Kakiuchi, F. & Jacobsen, E. N. Asymmetric catalysis with water: efficient kinetic resolution of terminal epoxides by means of catalytic hydrolysis. Science 277, 936–938 (1997).

    Article  CAS  Google Scholar 

  3. Zhu, S.-F., Chen, C., Cai, Y. & Zhou, Q.-L. Catalytic asymmetric reaction with water, enantioselective synthesis of α-hydroxyesters by a copper-carbenoid O–H insertion reaction. Angew. Chem. Int. Ed. 47, 932–934 (2008).

    Article  CAS  Google Scholar 

  4. El-Qisairi, A. Hamed, O. & Henry, P. M. A new palladium(II)-catalyzed asymmetric chlorohydrin synthesis. J. Org. Chem. 63, 2790–2791 (1998).

    Article  CAS  Google Scholar 

  5. Alper, H. & Hamel, N. Asymmetric synthesis of acids by the palladium catalyzed hydrocarboxylation of olefins in the presence of (R)-(–)- or (S)-(+)-1,1′-binaphthyl-2,2′-diyl hydrogen phosphate. J. Am. Chem. Soc. 112, 2803–2804 (1990).

    Article  CAS  Google Scholar 

  6. Gawron, O. & Fondy T. P. Stereochemistry of the fumarase and aspartase catalyzed reactions and of the Krebs cycle from fumaric acid to D-isocitric acid. J. Am. Chem. Soc. 81, 6333–6334 (1959).

    Article  CAS  Google Scholar 

  7. Willadsen, P. & Eggerer H. Substrate stereochemistry of enoyl-CoA hydratase reaction. Eur. J. Biochem. 54, 247–252 (1975).

    Article  CAS  Google Scholar 

  8. Agnihotri, G. & Liu, H. Enoyl-CoA hydratase: reaction, mechanism and inhibition. Bioorg. Med. Chem. 11, 9–20 (2003).

    Article  CAS  Google Scholar 

  9. Mohrig, J. R. et al. Importance of historical contingency in the stereochemistry of hydratase–dehydratase enzymes. Science 269, 527–529 (1995).

    Article  CAS  Google Scholar 

  10. Cornils, B. & Herrmann, W. A. Aqueous-Phase Organometallic Catalysis 2nd edn (Wiley, 2004).

  11. Lindström, U. M. Organic Reactions in Water (Blackwell, 2007).

  12. Noyori, R. et al. Asymmetric hydrogenation of β-keto carboxylic esters. A practical, purely chemical access to β-hydroxy esters in high enantiomeric purity. J. Am. Chem. Soc. 109, 5856–5858 (1987).

    Article  CAS  Google Scholar 

  13. Schetter, B. & Mahrwald, R. Modern aldol methods for the total synthesis of polyketides. Angew. Chem. Int. Ed. 45, 7506–7525 (2006).

    Article  CAS  Google Scholar 

  14. List, B., Lerner, R. A. & Barbas C. F. Proline-catalyzed direct asymmetric aldol reactions. J. Am. Chem. Soc. 122, 2395–2396 (2000).

    Article  CAS  Google Scholar 

  15. Nising, C. F. & Bräse S. The oxa-Michael reaction: from recent developments to applications in natural product synthesis. Chem. Soc. Rev. 37, 1218–1228 (2008).

    Article  CAS  Google Scholar 

  16. Vanderwall, C. D. & Jacobsen, E. N. Enantioselective formal hydration of α,β-unsaturated imides by Al-catalyzed conjugate addition of oxime nucleophiles. J. Am. Chem. Soc. 126, 14724–14725 (2004).

    Article  Google Scholar 

  17. Stewart, I. C., Bergman, R. G. & Toste, F. D. Phosphine-catalyzed hydration and hydroalkoxylation of activated olefins: use of a strong nucleophile to generate a strong base. J. Am. Chem. Soc. 125, 8696–8697 (2003).

    Article  CAS  Google Scholar 

  18. Roelfes, G. & Feringa, B. L. DNA-based asymmetric catalysis. Angew. Chem. Int. Ed. 44, 3230–3232 (2005).

    Article  CAS  Google Scholar 

  19. Roelfes, G., Boersma, A. J. & Feringa, B. L. Highly enantioselective DNA-based catalysis. Chem. Commun. 635–637 (2006).

  20. Coquière, D., Feringa, B. L. & Roelfes, G. DNA-based catalytic enantioselective Michael reactions in water. Angew. Chem. Int. Ed. 46, 9308–9311 (2007).

    Article  Google Scholar 

  21. Boersma, A. J., Feringa, B. L. & Roelfes, G. Enantioselective Friedel–Crafts reactions in water using a DNA-based catalyst. Angew. Chem. Int. Ed. 48, 3346–3348 (2009).

    Article  CAS  Google Scholar 

  22. Shibata, N., Yasui, H., Nakamura, S. & Toru, T. DNA-mediated enantioselective carbon–fluorine bond formation. Synlett 1153–1157 (2007).

  23. Fournier, P., Fiammengo, R. & Jäschke, A. Allylic amination by a DNA-diene–iridium hybrid catalyst. Angew. Chem. Int. Ed. 48, 4426–4429 (2009).

    Article  CAS  Google Scholar 

  24. Denmark, S. E., Winter, S. B. D., Su, X. & Wong, K.-T. Chemistry of trichlorosilyl enolates. 1. New reagents for catalytic, asymmetric aldol additions. J. Am. Chem. Soc. 118, 7404–7405 (1996).

    Article  CAS  Google Scholar 

  25. Heathcock, C. H. Stereodifferentiation addition reactions in Asymmetric Synthesis Vol. 3 (ed. Morrison, J. D.) Ch. 2 (Academic Press, 1984).

  26. Rosati, F. et al. A kinetic and structural investigation of DNA-based asymmetric catalysis using first-generation ligands. Chem. Eur. J. 15, 9596–9605 (2009).

    Article  CAS  Google Scholar 

  27. Bahnson, B. J., Anderson, V. E. & Petsko, G. A. Structural mechanism of enoyl-CoA hydratase: three atoms from a single water are added in either an E1cb stepwise or concerted fashion. Biochemistry 41, 2621–2629 (2002).

    Article  CAS  Google Scholar 

  28. Berman, H. M. & Schneider, B. in Oxford Handbook of Nucleic Acid Structure (ed. Neidle, S.) 295 (Oxford Univ. Press, 1999).

  29. Nguyen, B., Neidle, S. & Wilson, W. D. A role for water molecules in DNA-ligand minor groove recognition. Acc. Chem. Res. 42, 11–21 (2009).

    Article  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Stratingh Institute for Chemistry and Center for Systems Chemistry, University of Groningen, Nijenborgh 4, Groningen, 9747, AG, The Netherlands

    Arnold J. Boersma, David Coquière, Danny Geerdink, Fiora Rosati, Ben L. Feringa & Gerard Roelfes

Authors
  1. Arnold J. Boersma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Coquière
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Danny Geerdink
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fiora Rosati
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ben L. Feringa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gerard Roelfes
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 3905 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.819

  • Springer Nature Limited

This article is cited by

Search

Navigation