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This thesis will describe the development of a new route to homoallylic amines 9, in four steps from alcohols 1, or acetals 2, which may themselves have to be synthesised. The synthesis is stereoselective, and generates <i>E</i>-9 and <i>Z</i>-9 quite separately, thereby avoiding the sometimes difficult separation of these isomers. Alkenes 3, readily available from alcohols 1 or acetals 2, undergo regio- and stereo-selective 1,3-dipolar cycloadditions with nitrile oxides 4 or nitrones 6. The resulting heterocycles 5 and 7 are reductively cleaved to give β-hydroxy-δ-aminoalkyldiphenylphosphine oxides 8. These alcohols undergo Horner-Emmons-type elimination of sodium diphenylphosphinite to give homallylic amines 9, stereospecifically. Isoxazolines 5, resulting from nitrile oxide cycloadditions, undergo stereoselective reduction, and give rise to primary amines 9, R<SUP>3 =</SUP> H. Isoxazolines 7, resulting from nitrone cycloadditions, give rise to secondary amines 9, R<SUP>3 =</SUP> alkyl or aryl. When the alkoxy substituted alkenes 3, R<SUP>1 =</SUP> OR are used, protected enol ethers 9, R<SUP>1 =</SUP> OR, R<SUP>3 =</SUP> Ac are the final products. The vital cycloaddition and reduction steps are both high yielding, although the elimination is often less so.

This thesis is divided into two sections. In Section I, the desymmetrisation of a <i>meso-</i>cyclic anhydride was described. However, the transformation requires extremely low temperatures (-55°C) and a long reaction time (96 h) in order to achieve high enantioselectivity, which is not feasible for transfer into a continuous flow system. Later on, the work turned to investigation of its application towards the synthesis of chiral cyclopentanes using new enabling technologies. In Section II, the enantioselective Michael addition of aldehydes to nitroethylene in flow was described. The process was successfully incorporated into a flow system (R2+ and R4 unit). Key to this organocatalytic process is the use of catalytic amounts of a diphenylprolinol silyl ether catalyst with acetic acid as co-catalyst. This is an efficient catalytic system that enables faster transformation (1-3 h) with high enantioselectivities (up to 98% <i>ee</i>). A study on a proposed enol mechanism for this catalytic process was also discussed. Both sections provide full experimental procedures as well as characterisation in support of the results described within this thesis.

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This thesis is divided into five Chapters. The first consists of an introduction to dispiroketals and an overview of what has been achieved through their application in organic synthesis. The second Chapter describes the use of (<I>2S,2'S</I>)-2,2'-diphenyl-6,6'-bi-3,4-dihydro-<I>2H</I>-pyran to achieve the asymmetric synthesis of (+)-D-conduritol B. The synthesis proceeds in nine steps from DL-1-<I>0,2-0:4-O,5-O-</I>dicyclohexylidene-<I>myo</I>-inositol and the key step is the simultaneous protection and resolution of a racemic diol <I>via </I>dispiroketal methodology. The optical rotation of the final product, (+)-1D-Conduritol B, was found to differ significantly from literature reports, but the optical purity of our synthetic material was proved to be >98% using chiral gas chromatography. The third Chapter concerns work towards the synthesis of unsymmetrical bis-enol ethers and their use in dispiroketalisations. The synthetic approach to these compounds is a palladium-catalysed coupling of enol triflates with vinyl stannanes. Unusually, homocoupling of both partners was observed in addition to the desired heterocoupling but optimisation of conditions led to reasonable yields. The few dispiroketals possessing unsymmetrical alkyl substitution on the pyran rings are prepared. The fourth Chapter describes studies towards the development of an asymmetric reagent based on dispiroketals. A lithium aluminium hydride reduction modified with an enantioenriched dispiroketal-based diol gave a modest enantiomeric excess of product. A synthetic route to a dispiroketal-based secondary amine was developed in the racemic series, with a view to application of an enantioenriched version as a homochiral lithium amide base.

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