Dr. Nick Greeves

The University of Liverpool

Department of Chemistry

The Robert Robinson Laboratories

P.O. Box 147

LIVERPOOL L69 7ZD UK

Email: ngreeves@liv.ac.uk

via Eudora Pro 3.1 on PowerMacintosh 9500 @ 150 MHz

TEL NOS:- DIRECT +44 (0)151 794 3506

DEVELOPMENT OF NEW ASYMMETRIC SYNTHETIC METHODS FOR ORGANIC CHEMISTRY

Our research covers all aspects of organic synthesis, particularly the design, discovery, and development of new stereoselective reactions and the application of these synthetic methods to the construction of various biologically active natural products and structurally related molecules of interest. Opportunities exist for industrial collaboration with leading pharmaceutical companies on the testing of these materials.

New Synthetic Methods

There is a need for new and more efficient methods of synthesis, particularly those with high levels of stereocontrol. We are interested in using novel organometallic reagents and catalysts in important carbon-carbon bond forming reactions that will form the basis of synthetic strategy.

1. Acyclic Stereocontrol via Tandem Wittig-Anionic Oxy-Cope Rearrangement The combination of two established diastereoselective sigmatropic rearrangement reactions into a single powerful synthetic operation and its utility as a tool for natural product synthesis.

2. Enantioselective Organolanthanide Reagents and Catalysts. A new class of organocerium compounds, bearing optically pure "designer" diols as ligands to maximise enantioselectivity, as reagents and lanthanide complexes with neutral optically pure ligands as Lewis acid catalysts for asymmetric carbon-carbon bond formation.

3. Novel Methods for the Synthesis of Aromatic Heterocycles. Design and execution of novel methods for the synthesis of substituted five-membered heterocycles which appear structurally simple but possess significant biological activity.

4. Synthesis of Synthetic Pyrethroids and Intermediates. The development of new versatile approaches to the stereo- and enantioselective synthesis of cyclopropane carboxylic acid derivatives for application to synthetic pyrethroid preparation.

5. Enantioselective Diels-Alder Reactions of 2H-Pyrans. Preparation and study of the heterocyclic dienes, 2H-pyrans, with asymmetric dienophiles and Lewis acid catalysts. The optically pure oxabicyclic adducts are useful synthetic intermediates for a range of targets including thromboxanes.

Selected Recent References

  • `New Homochiral Binaphthol-Modified Organolanthanide Reagents for the Enantioselective Addition to Aldehydes', Tetrahedron Asymmetry, 1993, 4, 2407-2410.

  • `Ligand Effects on Diastereoselective Addition of Organocerium Reagents to Aldehydes and Cyclic Ketones', Tetrahedron Lett., 1994, 35, 285-288.

  • `Ytterbium Trifluoromethanesulfonate [Yb(OTf)3] as a Novel Catalyst for the Allylation of Aldehydes', Tetrahedron Lett. 1994, 4639-4640.

  • `Regioselective and Stereoselective Palladium(0) Catalyzed Hydrostannation of Disubstituted Propargyl Alcohols', Synlett 1994, 537-538.

  • `Stereoconvergent One-Pot Tandem [2,3]-Wittig-Anionic Oxy-Cope Rearrangement of Acyclic Bis-allylic Ethers in the Diastereoselective Synthesis of Substituted Tetrahydropyrans', J. Chem. Soc., Chem. Commun. 1994, 1469-1470.

  • `Acyclic Stereocontrol via Sequential and Tandem [2,3]-Wittig-Anionic Oxy-Cope Rearrangements', Tetrahedron Lett. 1994, 35, 7077-7080.

  • 'Enantioselective Addition Of Organocerium Reagents to Aldehydes - Effects Of Taddol Ligand Structure', N. Greeves and J.E. Pease, M.C. Bowden, S.M. Brown, Tetrahedron Lett. 1996, 37, 2675-2678.

  • 'Enantioselective Addition Of Tris(Taddol) Organocerium Reagents to Aldehydes', N. Greeves and J.E. Pease, Tetrahedron Lett. 1996, 37, 5821-5824.

  • 'An Improved Williamson Etherification of Hindered Alcohols Promoted by 15-Crown-5 and Sodium Hydride', H.C. Aspinall, N. Greeves, W-M. Lee, E.G. McIver, and P.M. Smith, Tetrahedron Lett. 1997, 38, in the press.

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