A Catalytic Asymmetric Cross-Coupling Approach to the Synthesis of Cyclobutanes

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Cyclobutanes are an important class of compounds, which have a number of uses in the chemical industry. There are currently forty-three approved or candidate molecules in the drug discovery pipeline which contain the cyclobutane functionality. Cyclobutanes also appears in a number of natural products and fine chemicals. Methods to access this privileged class of compounds are however not very well developed and there is a pressing need to develop novel synthetic strategies, both to access novel cyclobutane scaffolds and to allow existing ones to be made more efficiently.An asymmetric metal-catalysed transformation is an efficient method to build a complex carbon skeleton from simple components, using only a very small quantity of metal and ligand. The successful development of such transformations revolutionises the molecules available to industry for the development of new medicines, new fragrances, new materials, and new catalysts. In building a complex carbon skeleton, we often come across difficulties in controlling the 3D arrangement. An enantioenriched product is a product in which only one, highly specific, 3D shape is selected for, and this represents a significant challenge to chemists in the production of pharmaceutical treatments and other complex molecules. This project aims to develop novel transformations which provide efficient access to a diverse array of enantioenriched cyclobutanes and other similar compounds, with focus on making the type of sp3-rich molecules that are essential for the development of new medicines.The objectives of this project are to develop technology to enable: i) the synthesis of chiral cyclobutane derivatives, similar to the structures found in a number of biologically active molecules and approved drugs; ii) a greater understanding of the mechanism by which this transformation is occurring, allowing us to further optimise and expand the reaction; iii) the synthesis of biologically active compounds, showcasing the utility of these novel methods and their applicability to medicine; iv) the synthesis of other enantioenriched scaffolds, including nitrogen heterocycles and multiple fused-ring systems, which would greatly expand the classes of 4 membered ring containing structures that can be easily prepared.The work develop a new strategy for the efficient preparation of cyclobutanes and then work will be conducted to increase our understanding of how the chemistry operates so that the reactions can be optimized and inspire us to tackle even more ambitious projects in the future. By developing and expanding the scope of this technology in this way, we significantly increase its value to the pharmaceutical industry and other end users of the technology. Finally, being able to access a diverse range of novel chiral materials will enable the discovery of new medicines, fragrances, materials and catalysts that would otherwise be inaccessible.