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.
Subscribe to Journal
Get full journal access for 1 year
only $13.33 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Silverman, R. B. The Organic Chemistry of Enzyme Catalyzed Reactions Ch. 10 (Academic Press, 2000).
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).
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).
El-Qisairi, A. Hamed, O. & Henry, P. M. A new palladium(II)-catalyzed asymmetric chlorohydrin synthesis. J. Org. Chem. 63, 2790–2791 (1998).
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).
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).
Willadsen, P. & Eggerer H. Substrate stereochemistry of enoyl-CoA hydratase reaction. Eur. J. Biochem. 54, 247–252 (1975).
Agnihotri, G. & Liu, H. Enoyl-CoA hydratase: reaction, mechanism and inhibition. Bioorg. Med. Chem. 11, 9–20 (2003).
Mohrig, J. R. et al. Importance of historical contingency in the stereochemistry of hydratase–dehydratase enzymes. Science 269, 527–529 (1995).
Cornils, B. & Herrmann, W. A. Aqueous-Phase Organometallic Catalysis 2nd edn (Wiley, 2004).
Lindström, U. M. Organic Reactions in Water (Blackwell, 2007).
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).
Schetter, B. & Mahrwald, R. Modern aldol methods for the total synthesis of polyketides. Angew. Chem. Int. Ed. 45, 7506–7525 (2006).
List, B., Lerner, R. A. & Barbas C. F. Proline-catalyzed direct asymmetric aldol reactions. J. Am. Chem. Soc. 122, 2395–2396 (2000).
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).
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).
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).
Roelfes, G. & Feringa, B. L. DNA-based asymmetric catalysis. Angew. Chem. Int. Ed. 44, 3230–3232 (2005).
Roelfes, G., Boersma, A. J. & Feringa, B. L. Highly enantioselective DNA-based catalysis. Chem. Commun. 635–637 (2006).
Coquière, D., Feringa, B. L. & Roelfes, G. DNA-based catalytic enantioselective Michael reactions in water. Angew. Chem. Int. Ed. 46, 9308–9311 (2007).
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).
Shibata, N., Yasui, H., Nakamura, S. & Toru, T. DNA-mediated enantioselective carbon–fluorine bond formation. Synlett 1153–1157 (2007).
Fournier, P., Fiammengo, R. & Jäschke, A. Allylic amination by a DNA-diene–iridium hybrid catalyst. Angew. Chem. Int. Ed. 48, 4426–4429 (2009).
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).
Heathcock, C. H. Stereodifferentiation addition reactions in Asymmetric Synthesis Vol. 3 (ed. Morrison, J. D.) Ch. 2 (Academic Press, 1984).
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).
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).
Berman, H. M. & Schneider, B. in Oxford Handbook of Nucleic Acid Structure (ed. Neidle, S.) 295 (Oxford Univ. Press, 1999).
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).
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.
The authors declare no competing financial interests.
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
Doublet Chirality Transfer and Reversible Helical Transition in Poly(3,5‐disubstituted phenylacetylene)s with Pyrene as a Probe Unit †
Chinese Journal of Chemistry (2020)
An Efficient Cyclic Di-AMP Based Artificial Metalloribozyme for Enantioselective Diels-Alder Reactions
European Journal of Organic Chemistry (2020)
Chinese Journal of Chemical Engineering (2020)
Highly Efficient Cyclic Dinucleotide Based Artificial Metalloribozymes for Enantioselective Friedel–Crafts Reactions in Water
Angewandte Chemie International Edition (2020)