Chapter 1 describes an introduction to the area of organocatalysis and delineates previous work within the Smith group on the use of isothioureas in asymmetric catalysis. Chapter 2 showcases a one-pot isothiourea-catalysed Michael addition-lactamisation using cheap and readily available starting materials (carboxylic acids) and easily prepared α,β-unsaturated ketimines via an ammonium enolate intermediate to give dihydropyridinones with high diastereo- and enantioselectivity (typically >90:10 dr, up to 99% ee). The resultant dihydropyridinones can be successfully derivatised into multiple products without erosion of stereointegrity. In chapter 3 the same concept has also been applied to the synthesis of planar molecules by using (phenylthio)acetic acid as a suiTable ammonium enolate precursor. Generation of an ammonium enolate using an achiral isothiourea (DHPB) and reaction with α,β-unsaturated trifluoromethyl ketones allows an isothiourea-mediated Michael addition / lactonisation / thiophenol elimination cascade reaction for the formation of 4,6-disubstituted and 3,4,6-trisubstituted 2-pyrones in good to excellent yields (61-99%). Notably this method allows low catalyst loadings of 1% to be used. The methodology has successfully been applied to the synthesis of a COX-2 inhibitor and a wide range of derivatisations has been performed, giving valuable aromatic and heteroaromatic products containing the trifluoromethyl motif. In chapter 4 a novel N- to C-sulfonyl migration of dihydropyridinones via photoisomerisation is investigated. The scope and limitations of this process is investigated and the process is shown to proceed without compromising the diastereo- or enantiomeric purity of the starting material, giving 5-sulfonyl products in good to excellent yields (67-95%). Mechanistic crossover has indicated that this migration includes an intermolecular step, while EPR studies provided evidence of its radical nature.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:730663 |
| Date | January 2015 |
| Creators | Yeh, Pei-Pei |
| Contributors | Smith, Andrew David |
| Publisher | University of St Andrews |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/10023/11961 |
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