ASYMMETRIC TRANSFER HYDROGENATION USING TETHERED LIGANDS

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Many molecules can exist in one of a pair of mirror-images, or 'enantiomers', rather like a pair of hands. Many of the molecules which make up biological organisms (microbes, plants, animals, us...) exist only in a single enantiomer form. These include amino acids (which are used to make peptides and enzymes in the body), carbohydrates, and the chain of DNA (which also has a spiral with a single handedness). Anything we consume interacts with the molecules which make up our bodies. Because the molecules in our bodies are 'one handedness' then each of a pair of enantiomers will interact differently. As a result, there are many cases of enantiomeric molecules where one enantiomer has beneficial properties whilst the other may have none at all, or even be harmful. As a result, any new pharmaceutical compounds, or indeed any new molecular entities with the potential to exist as enantiomers, must be preparable in single-enantiomer form. This is challenging for the synthetic chemist, but represents one of the most important objectives of contemporary synthetic chemistry.In previous work, we have developed catalysts for the conversion of readily-available starting materials (ketones) into predominantly one handedness of an enantiomeric product (alcohols). In some cases the selectivity is very high. However in other cases it is not. In this proposal, we propose several modifications to our catalysts which are predicted to make them more appropriate for the reduction of a much wider series of substrates, thus increasing their overall usefulness. In the long term our objective is to develop ways of modifying our catalysts so that they can be employed for the selective synthesis of pure enantiomers of any desired target. This project represents an important step towards this objective.