| Summary: | This thesis details research into the mechanism of the copper-catalysed cross-coupling reaction, with a focus on the N-arylation of secondary amines and amides (Ullmann-Goldberg reaction). Issues limiting the application of the Ullmann-Goldberg reaction on industrial scale are uncovered and understood from a mechanistic point of view, to provide a platform for more efficient copper catalysts. In situ kinetic monitoring using 1H NMR spectroscopy is used to understand the role of each key component in the N-arylation of piperidine using a copper catalyst in a fully homogeneous system. Key roles of the amine and catalyst are observed, whilst product inhibition was found to significantly inhibit the reaction. Solvent effects are evaluated by repeating the in situ kinetic investigation in d7-DMF and d3-MeCN. The kinetic findings indicate deviation of the mechanism from the accepted literature mechanism, with a rate-limiting amine coordination proposed. Kinetic studies are also used to show the key role that the solubility of inorganic bases such as Cs2CO3 and K3PO4 play in rate-determining equilibria between copper species. Slow catalyst turnover was observed for up to 14 hours at lowered catalyst loadings, before a dramatic increase in the rate of reaction. A link between particle size, solubility and the deprotonation of the cyclic amide substrate are made, with the results having important implications on the use of inorganic bases in cross-coupling reactions. Inhibition of the reaction from inorganic side products and precipitation of copper from solution is combined with findings of a novel interaction between copper and cesium cation to give evidence for a non-innocent role of the cesium cation in copper-catalysed N-arylation. Heterogeneous catalysis is explored, where it is shown that copper precipitated from the reaction is capable of catalysis, introducing a question of a pseudo-heterogeneous mechanism and phase equilibria. A multi-edge XAFS (X-ray absorption fine structure) study is combined with laboratory experiments to uncover the activation, deactivation and reactivation pathways of an immobilised iridium transfer hydrogenation catalyst. The key role of an Ir-Cl bond is shown, where initial ligand exchange activates the catalyst, followed by further, slow ligand exchange, leading to deactivation of the catalyst.
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