Article | Published:

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

Nature Chemistry volume 2, pages 991995 (2010) | Download Citation

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.

  • Compound C11H16N2O

    (E)-4,4-Dimethyl-1-(1-methyl-1H-imidazol-2-yl)-2-penten-1-one

  • Compound C8H10N2O

    (E)-1-(1-Methyl-1H-imidazole-2-yl)-but-2-en-1-one

  • Compound C10H14N2O

    (E)-1-(1-Isopropyl-1H-imidazol-2-yl)but-2-en-1-one

  • Compound C12H18N2O

    (E)-1-(1-Methyl-1H-imidazole-2-yl)oct-2-en-1-on

  • Compound C10H14N2O

    (E)-4-Methyl-1-(1-methyl-1H-imidazole-2-yl)-pent-2-en-1-one

  • Compound C13H12N2O

    (E)-(1-Methyl-1H-imidazole-2-yl)-3-phenylprop-2-en-1-one

  • Compound C11H18N2O2

    (R)-3-Hydroxy-4,4-dimethyl-1-(1-methyl-1H-imidazol-2-yl)pentan-1-one

  • Compound C11H18N2O2

    (S)-3-Hydroxy-4,4-dimethyl-1-(1-methyl-1H-imidazol-2-yl)pentan-1-one

  • Compound C8H12N2O2

    3-Hydroxy-1-(1-methyl-1H-imidazol-2-yl)butan-1-one

  • Compound C10H16N2O2

    3-Hydroxy-1-(1-isopropyl-1H-imidazol-2-yl)-1-butanone

  • Compound C12H20N2O2

    3-Hydroxy-1-(1-methyl-1H-imidazol-2-yl)octan-1-one

  • Compound C10H16N2O2

    3-Hydroxy-4-methyl-1-(1-methyl-1H-imidazol-2-yl)pentan-1-one

  • Compound C13H14N2O2

    3-Hydroxy-1-(1-methyl-1H-imidazol-2-yl)-3-phenylpropan-1-one

  • Compound C11H16D2N2O2

    (R,R)-2-Deutero-3-hydroxy-4,4-dimethyl-1-(1-methyl-1H-imidazol-2-yl)pentan-1-one

  • Compound C11H17DN2O2

    (S,R)-2-Deutero-3-hydroxy-4,4-dimethyl-1-(1-methyl-1H-imidazol-2-yl)pentan-1-one

  • Compound C11H15DN2O

    (E)-4,4-Dimethyl-1-(1-methyl-1H-imidazol-2-yl)-2-deutero-2-penten-1-one

  • Compound C12H12N2

    4,4'-Dimethyl-2,2'-bipyridine

  • Compound C30H30N4O2

    N1-(9-Acridinyl)-N2-(3,5-dimethoxybenzyl)-N2-(2-pyridinylmethyl)-1,2-ethanediamine

  • Compound C31H32N4O2

    N1-(9-Acridinyl)-N3-(3,5-dimethoxybenzyl)-N3-(2-pyridinylmethyl)-1,3-propanediamine

  • Compound C32H28N4

    N1-(9-Acridinyl)-N2-(1-naphthylmethyl)-N2-(2-pyridinylmethyl)-1,2-ethanediamine

  • Compound C33H30N4

    N1-(9-Acridinyl)-N3-(1-naphthylmethyl)-N3-(2-pyridinylmethyl)-1,3-propanediamine

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

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

  2. 2.

    , , & Asymmetric catalysis with water: efficient kinetic resolution of terminal epoxides by means of catalytic hydrolysis. Science 277, 936–938 (1997).

  3. 3.

    , , & 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).

  4. 4.

    & A new palladium(II)-catalyzed asymmetric chlorohydrin synthesis. J. Org. Chem. 63, 2790–2791 (1998).

  5. 5.

    & 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).

  6. 6.

    & 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).

  7. 7.

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

  8. 8.

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

  9. 9.

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

  10. 10.

    & Aqueous-Phase Organometallic Catalysis 2nd edn (Wiley, 2004).

  11. 11.

    Organic Reactions in Water (Blackwell, 2007).

  12. 12.

    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).

  13. 13.

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

  14. 14.

    , & Proline-catalyzed direct asymmetric aldol reactions. J. Am. Chem. Soc. 122, 2395–2396 (2000).

  15. 15.

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

  16. 16.

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

  17. 17.

    , & 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).

  18. 18.

    & DNA-based asymmetric catalysis. Angew. Chem. Int. Ed. 44, 3230–3232 (2005).

  19. 19.

    , & Highly enantioselective DNA-based catalysis. Chem. Commun. 635–637 (2006).

  20. 20.

    , & DNA-based catalytic enantioselective Michael reactions in water. Angew. Chem. Int. Ed. 46, 9308–9311 (2007).

  21. 21.

    , & Enantioselective Friedel–Crafts reactions in water using a DNA-based catalyst. Angew. Chem. Int. Ed. 48, 3346–3348 (2009).

  22. 22.

    , , & DNA-mediated enantioselective carbon–fluorine bond formation. Synlett 1153–1157 (2007).

  23. 23.

    , & Allylic amination by a DNA-diene–iridium hybrid catalyst. Angew. Chem. Int. Ed. 48, 4426–4429 (2009).

  24. 24.

    , , & Chemistry of trichlorosilyl enolates. 1. New reagents for catalytic, asymmetric aldol additions. J. Am. Chem. Soc. 118, 7404–7405 (1996).

  25. 25.

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

  26. 26.

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

  27. 27.

    , & 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).

  28. 28.

    & Oxford Handbook of Nucleic Acid Structure (ed. Neidle, S.) 295 (Oxford Univ. Press, 1999).

  29. 29.

    , & A role for water molecules in DNA-ligand minor groove recognition. Acc. Chem. Res. 42, 11–21 (2009).

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

Affiliations

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

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

Authors

  1. Search for Arnold J. Boersma in:

  2. Search for David Coquière in:

  3. Search for Danny Geerdink in:

  4. Search for Fiora Rosati in:

  5. Search for Ben L. Feringa in:

  6. Search for Gerard Roelfes in:

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.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Ben L. Feringa or Gerard Roelfes.

Supplementary information

PDF files

  1. 1.

    Supplementary information

    Supplementary information

About this article

Publication history

Received

Accepted

Published

DOI

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

Further reading