Complexity-Generating Hydration Reactions via Metal-Catalysed Reaction of Boronic Acids with Alkenes

Simple organic molecules containing carbon-carbon double bonds, known as alkenes, are widely available bulk chemicals that serve as basic starting materials for the synthesis of a wide range of more complex molecules with useful properties - pharmaceuticals, fine chemicals, agrochemicals, polymers, etc. In this proposal we outline new catalytic strategies for the direct conversion of alkenes into complex molecular structures. In each case, a novel sequence of reactions is initiated via the formal addition of a molecule of water across the carbon-carbon double bond of the alkene (a hydration reaction). The reaction of water with an alkene can be difficult to accomplish as many alkenes do not dissolve in water. It is usually achieved using either strong acids (e.g. sulfuric acid) or mercury salts (which are very toxic). In this research we will employ a new strategy based upon previous work from our laboratory in which the water molecule is attached to an organic boron-containing compound, enabling it to be 'dissolved' in an organic solvent and to react more readily in the presence of a suitable catalyst (In this project more efficient and considerably less toxic catalysts based around metals such as palladium, platinum and gold will be used - our preliminary experiments have demonstrated that such catalysts are effective). This strategy is potentially very powerful as the boron atom can be used in further (post-hydration) chemical reactions to construct complex products. These new reaction strategies will be of use for the synthesis of a wide range of products including molecules of interest for screening against disease targets in medical research. This will enable us to build up collaborations with appropriate biologists in order to apply our new discoveries in the development of new medical treatments.

The new catalytic methods outlined in this proposal will benefit scientists working in a variety of fields worldwide. In the first instance, chemists working on the synthesis of a wide range of molecules with useful properties in academia, the charity sector (e.g. medical research charities) and industry will be able to employ these new processes to enable them to construct more complex molecules with greater efficiency. The end users of these molecules working in other disciplines including chemical biology, biomedical science, polymer and materials synthesis, molecular signalling, medical imaging, catalysis, drug discovery, electronics, supramolecular chemistry and nanotechnology will then be able to explore the application of these newly available molecules in their research. Subsequently, fine chemical suppliers will be able to exploit these reactions for the synthesis of valuable chemical products for commercial supply. This in turn will make the end products of the chemistry readily available to the global scientific community.
The new catalytic reactions developed in this work are likely to offer more efficient routes to existing molecules of industrial/commercial importantance. This will therefore bring environmental benefits by reducing the impact of their synthesis on the global environment (fewer waste products, lower energy consumption, lower CO2 emissions from waste disposal, etc).
Where appropriate, valuable reactions/catalysts will be protected by patents in order to generate financial returns via licensing of the technology to an appropriate commercial partner, or via formation of a spin-out company. Ultimately such arrangements will benefit the UK economy via creation of new skilled jobs and contribute to economic growth and wealth generation. The increased availability of novel and complex molecules will assist researchers in the discovery and development of new medical treatments, eventually leading to health and well being benefits for the UK population.