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Enantioselective Synthesis of Ester Oxidation State Compounds via Organocatalysis and Biocatalysis

thesis
posted on 15.03.2017 by Jacob Grant
Esters, and other carbonyls in the ester oxidation state (e.g. acyl chlorides, anhydrides), are widely used in organic synthesis. Catalysis of these substrates by N-heterocyclic carbenes (NHCs) is underdeveloped compared to catalysis of lower oxidation state carbonyls. This thesis focuses on the catalysis of ester oxidation state substrates by NHCs, with a secondary focus on enzyme catalysed reactions of similar substrates.
   The first chapter contains a review of the literature concerning N-heterocyclic carbene catalysed reactions of compounds in the ester oxidation state. The review is organised by the reactive intermediate generated by addition of the NHC to the substrate.
   Chapter two describes the development of an enantioselective NHC-catalysed Claisen rearrangement to synthesise dihydropyranone products. After optimisation of conditions to obtain the dihydropyranones in the highest possible enantiomeric ratios, the generality of the reaction was examined. Attempts to extend the substrate scope to encompass additional heteroatomic variants are also detailed. Finally, the preliminary development of an NHC-catalysed dual-Claisen condensation/rearrangement is described, in which analogous species to the Claisen rearrangement substrate are formed in situ from simple starting materials.
   In the third chapter, a collaborative project with researchers at the Australian National University is described. Mutant organophosphorus hydrolase enzymes are trialled as enantioselective catalysts for kinetic resolutions of esters and phosphoesters, as well as Michael additions to α,β-unsaturated carbonyl compounds.
   The final chapter details experimental methods and spectral data for the compounds synthesised over the course of these projects.

History

Campus location

Australia

Principal supervisor

David Lupton

Additional supervisor 1

Chris Thompson

Year of Award

2017

Department, School or Centre

Chemistry

Faculty

Faculty of Science

Exports

Exports