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This thesis describes two research projects aimed at the design and development of new methods for the construction of carbon-carbon bonds. The first focused on attempts to extend previous work within the Spring Group on the formation of biaryl-containing medium rings <i>via</i> the oxidative coupling of organocuprates to the formation of dienyl and alkenyl medium rings. It was found that functionalised alkenylsilanes bearing a pendant coordinating group could be prepared with good control over the geometry of the alkene, and undergo stereospecific fluoride-mediated transmetalation to copper followed by thermolytic or oxidative dimerisation of the so-formed alkenylcopper species to yield symmetrical dienes. Unfortunately, despite considerable effort, it was not possible to extend this finding to an intramolecular medium ring-forming variant of this reaction. The goal of the second project was to develop a novel catalytic soft enolisation – S<i>_N</i>2 alkylation reaction carbonyl compounds. Preliminary screens of various established Lewis acids, bases, and ligands did not provide any useful hits, and so a computational study was undertaken to develop a better understanding of the desired reaction and to identify means by which it might be promoted. This study suggested that a bifunctional Lewis acid catalyst bearing a pendant quaternary ammonium ion might offer a solution to the problem at hand, and so a small library of such ligands was synthesised. A computational study of the proposed reaction identified two key flaws in the original reaction and ligand design and led to the design of a new ligand.

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Chapters 1 and 2: An introduction to the intermolecular oxy-Michael reaction and a brief overview of the methods used to synthesise 1,2-amino alcohols. Chapter 3: An oxy-Michael reaction was developed whereby the addition of (<i>S</i>)-6-methyltetrahydropyran into a,b-unsaturated monosubstituted nitro compounds allowed rapid access to synthetically important 1,2-amino alcohols. Chapter 4: A logical advancement of the oxy-Michael addition was the addition into a,b-unsaturated disubstituted nitro compounds. These molecules were also converted into the corresponding 1,2-amino alcohols. In addition sequential treatment of the oxy-Michael adduct with TPAP yielded the corresponding b-hydroxy ketone motif. Chapters 5 and 6: The highly stereoselective total syntheses of (<i>R</i>)-pronethalol and (<i>R</i>)-salmeterol were achieved using the new oxy-Michael method as the key step. Chapter 7: An expansion of the methodology to incorporate other conjugate acceptors was considered important. However, analogous d-lactol oxy-Michael additions into crotonate ester and pentenolide were unsuccessful. However, successful oxy-Michael addition into symmetrical a,b-unsaturated malonate systems yielded THP* protected b-hydroxy malonates. It is believed that such motifs shall be capable of transformation into b-hydroxy esters after further development.