Abstract
The research in this thesis describes the development of α-aroyloxyaldehydes as bench-stable precursors to the azolium enolate intermediate in N-heterocyclic carbene (NHC) catalysis and the subsequent application of this system to a number of different reaction partners in asymmetric catalytic processes.Chapter 1 aims to place this research in context with respect to the literature, both current and historical, offering a contrast between the described approach, and that undertaken by other research groups across the world. The historical context of this project in terms of research within the Smith group is also presented, as is a statement of the initial aims and objectives of the research project.
Chapter 2 describes the investigation of a model system using β,γ-unsaturated α-keto esters to gain an initial insight into the reactivity and develop an understanding of the α-aroyloxyaldehyde system.
Chapter 3 describes the application of the α-aroyloxyaldehyde-NHC system to a novel class of Michael acceptors, β’-trifluoromethylenones, to generate dihydropyranone products containing stereogenic trifluoromethyl groups. The adoption of (Z)-β’-trifluoromethylenones as reaction partners has confirmed the reaction as stereospecific, and also disclosed within this chapter is an examination of the mechanism of this process through kinetic studies.
Chapter 4 describes the further development of the α-aroyloxyaldehyde-NHC system to synthesise C(5) substituted dihydropyranones, rarely reported in the NHC catalysis literature, through a [4+2] cycloaddition with α-trifluoromethylenones. Also disclosed is the application of a substrate controlled hydrogenation of the C(5) substituted dihydropyranones to the corresponding δ-lactones, and the substrate controlled reduction of C(5) unsubstituted dihydropyranones to δ-lactols.
Chapter 5 describes the development and optimisation of a formal [2+2] cycloaddition between α- aroyloxyaldehydes and trifluoroacetophenones under NHC catalysis. The β-lactone products expected proved to be unstable and therefore a number of different nucleophiles were applied to the system in order to generate β-hydroxyamides and 1,3-diols.
Chapter 6 describes the further development of the formal [2+2] cycloaddition system through the adoption of pentafluoroethyl and perfluorobutyl ketones, providing the β-hydroxyamide and 1,3-diol products in improved yield and diastereoselectivity compared with their trifluoromethyl analogues. The derivatisation of the 1,3-diol products to oxetanes in a one-step procedure is also shown.
Chapter 7 offers a brief summary of the work undertaken and the conclusions that can be drawn from it.
Chapter 8 offers an insight into the potential future developments of this research, and also provides examples of concurrent work undertaken both within and outside of the Smith group on the use of α- aroyloxyaldehydes in NHC catalysis.
| Date of Award | 22 Jun 2016 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Andrew Smith (Supervisor) |
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