Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.720659
Title: Selective catalytic C-H functionalisation for drug discovery
Author: Paterson, Andrew
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 2017
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Abstract:
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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.720659  DOI: Not available
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