Since their discovery in the early 1900s by Fritz Ullmann, copper-catalysed C-N cross-coupling
reactions have been widely investigated in both academic and industrial settings. While the
discovery of oxalamide ligands by Ma et al. has advanced the Ullmann reaction by increasing
the substrate scope and improving reaction conditions, greater advancement has been
stunted by limited understanding of the reaction mechanism. The work in this thesis attempts to clarify the mechanism of the Ullmann C-N cross-coupling reaction. In Chapter 2, kinetic studies were performed on a successful Cu/oxalamide-catalysed C-N
cross-coupling reaction. It was found that catalyst deactivation occurred at low loadings of copper, while increased loadings of ligand prevented deactivation. This led to improved
reaction conditions whereby the ligand was employed in large excess while copper loadings
could be decreased to as low as 5 ppm for a range of substrates. TONs of 6.88 × 104
and 1.9 × 105 were achieved with an aryl bromide and iodide substrate respectively. The
reaction was first order in [aryl bromide], zero order in [amine] and [base], and first order in
[copper] and [ligand].
In Chapter 3, the role of the oxalamide ligand was investigated. The ligand did not show
evidence of inducing formation of the active CuI species, but the base, KOH, was able to
reduce CuII species, indicating its role in the formation or recycling of the active catalytic
species. A multiple addition experiment with the ligand proved the ligand is being consumed
during the reaction, but the nature of this process could not be determined.
In Chapter 4, alternative ligands were investigated in the reaction conditions employed in Chapters 2 and 3. The ligands employed were not as effective as the asymmetric oxalamide ligands, since the yields obtained were much lower, and, generally, higher copper and ligand
loadings were required.