A New Family of Powerful Asymmetric Bifunctional Organocatalysts and their Reactions

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Certain organic molecules have non-flat 3 dimensional structures which have the inherent property of not being superimposable on their own mirror images. Such a molecule is said to be chiral and the two mirror images are known as enantiomers. These enantiomers behave identically in nearly all situations except when placed in a chiral environment like those found inside biological systems, such as cells, receptors and enzymes. Accordingly one enantiomer of a bioactive chiral compound may elicit very different biological responses with sometimes catastrophic consequences. As a result, chemists have been seeking to discover the perfect reaction that will allow the creation (or synthesis) of such chiral compounds as single enantiomers, not mixtures of them. Chiral compounds may be synthesised by adding one compound to another 'flat' compound such as one containing a carbon-carbon double bond (or alkene), a carbon-nitrogen double bond (or imine), a carbon-oxygen double bond (aldehyde or ketone). The addition reaction destroys the planarity and results in the chiral product, but as addition to each face of the alkene is equally likely, an equal amount of both enantiomers is formed (a racemic mixture). Influencing the reaction to lead to a predominance of one enantiomer (known as asymmetric synthesis) is possible by using additional external chiral reagents or catalysts. These catalysts often affiliate with the flat substrate and prevent or promote, to some extent, an addition reaction of a reagent to one or other of the faces of the alkene, imine or aldehyde. In this proposal we wish to build on some preliminary studies, which have shown that a new type of chiral bifunctional catalyst can simultaneously activate the substrate and reagent and facilitate an efficient reaction between them. This enzyme-like process allows the selective formation of the product as predominantly one enantiomer. We now wish to explore the potential and scope of this chemistry by creating a large family of related catalysts to promote new and important types of reaction with excellent enantiocontrol and apply the findings in the synthesis of biologically active compounds. As the numbers of substrates and reagents amenable to this type of catalysis is large, the potential number of new reactions to be discovered is enormous. Fortunately, the design of our system allows for easy chemical modification and hence simple coarse or fine tuning of the catalyst's structure and reactivity profile. This will ultimately allow one particular catalyst to be matched to a given reagent/substrate pair and facilitate bond formation with high enantiocontrol.Unlike many other efficient chiral catalysts in the literature this family benefits from being made of purely organic materials and is free from metal ions. This makes them easy to synthesise, easy to handle, cheap and less toxic than their metal ion counterparts. Accordingly these new environmentally friendly catalysts and their reactions will be of great value to chemists in industry and academia alike.