This thesis details the current methods for meta-selective C-H functionalisation and contains three chapters relating to the area of ruthenium catalysed meta selective functionalisation by σ-activation.The first of which contains a published manuscript entitled “Catalytic meta-selective C-H functionalization to construct quaternary carbon centres” and describes a meta selective tertiary alkylation procedure on 2-phenylpyridine substrates. Key findings from this work provide good evidence for a radical based mechanism and proposes a catalytic cycle involving two distinct roles for the ruthenium catalyst; both in the activation of the substrate molecule and in the formation of a tertiary radical coupling partner. The second chapter contains another published manuscript entitled “Mechanistic insight into ruthenium catalysed meta-sulfonation of 2-phenylpyridine” and provides mechanistic analysis for the meta selective sulfonation of 2-phenylpyridine. Key findings from this work show through stoichiometric experiments that sulfonation occurs at the position para to the C-Ru bond formed following cyclometalation with a radical addition being implied. The work also shows that the catalytic species involved do not require an arene ligand and deuterium labelling studies identified a likely rate limiting radical sulfonation step.The final chapter contains additional work relating to the use of α-halo carbonyl coupling reagents to enable meta selective primary, secondary and tertiary alkylations. The use of a triphenylphosphine ligand source was necessary for the coupling of primary α-halo carbonyl coupling partners at the meta position. Crucially, this transformation was not possible with simple, straight-chain alkyl halides, highlighting the privileged reactivity of α-halo carbonyl coupling reagents. This work also contains experimental and computational mechanistic analysis which reveals additional support for a dual activation pathway.
|Date of Award
|27 Jun 2017
|Novartis Institutes for BioMedical Research, Horsham
|Christopher Frost (Supervisor)