| EPSRC Reference: |
GR/M08226/01 |
| Title: |
TUNEABLE LEWIS ACID LANTHANIDE CATALYSTS AND THE ENANTIOSELECTIVETANDEM ALDOL-TISHCHENKO REACTION HA09 |
| Principal Investigator: |
Scott, Professor P |
| Other Investigators: |
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| Project Partners: |
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| Department: |
Chemistry |
| Organisation: |
University of Warwick |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
01 October 1998 |
Ends: |
31 October 2001 |
Value (£): |
159,378
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| EPSRC Research Topic Classifications: |
| Catalysis & Applied Catalysis |
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| EPSRC Industrial Sector Classifications: |
| Pharmaceuticals and Biotechnology |
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| Panel History: |
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Summary on Grant Application Form |
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We will prepare a range of well defined, water and air-tolerant chiral-non-racemic catalysts incorporating group 3/lanthanide ions and biaryl-bridged quadridentate ligands. These catalysts will be characterised by spectroscopic methods (such as UV/vis/nIR/IR, nOe NMR and FTICR/MS) and X-ray crystallography with the aim of defining their steric and electronic properties. This catalyst system will be used in the novel aldol-Tishchenko reaction to prepare 1, 3-diols and related compounds in clean 1-pot procedures. Different classes of substraint will allow us to optimise the catalysts for individual steps and, for example, to maximise enantioselection and 1, 2- and 1, 3-diastereoselection.Organic products will be analysed by spectroscopic methods and in particular by chiral HPLC and GC. This latter data will by particularly useful in giving feedback for optimisation of metal ionic radius and steric profile of the ligand.New Abstract:The production of racemic aldol-Tischenko products was accounted for in the discovery that the reaction was decelerated by the presence of the chiral ligands. This phenomenon is proposed (on the basis in-situ FTICR experiments and crystallographic studies on related metal complexes) to arise in the predominance of species with supramolecular bimetallic helicate structures which do not have accessible coordination sites. It was found however that anhydrous Sc(OTf)3 catalyses the 1,3-anti diastereoselective (>95%) reduction of R-hydroxyketones to 1,3-diol esters using aldehyde as reducing agent. A strategic decision was therefore taken to apply the ligand design principle to the study of other enantioselective reactions commensurate with the broader of the proposal and the spirit of the Catalysis & Catalytic Processes programme, viz enantioselective group transfer catalyses.The origins of a dramatic variation in catalyst efficiency in copper-catalysed alkene aziridination were delineated and well expressed chiral environments were thereby designed. A highly enantioselective catalytic system (cases of ee > 99%) was thereby developed. The structure of the active site and the nature of the selectivity-determining step were outlined.The speciation issue which plagued the Tishchenko reaction also presented itself in the related alkene cyclopropanation reaction, where lower enantioselection was observed. This catalytic problem was also solved through design of more substitutionally stable ruthenium system which gave an unprecedented combination of excellent enantio- (98%) and diastereoselectivity (99%) in the intermolecular reaction. The origin of this remarkable result was determined to be an unusual bidentate coordination mode in the active catalyst. Other mechanistic studies were also undertaken. An intermolecular cyclopropanation reaction was also successful.The final group transfer reaction of aziridination was found to be generally unsuccessful using the biaryl ligands because of their propensity to undergo radical damage. New systems were designed and funding was secured for their future study.
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Key Findings |
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Potential use in non-academic contexts |
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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| Further Information: |
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| Organisation Website: |
http://www.warwick.ac.uk |