The work described herein is concerned with the [3+2] dipolar cycloaddition of amino acid derived azomethine ylids. Such cycloadditions are a highly efficient technique for the construction of proline derivatives, and may potentially be employed in other areas of asymmetric synthesis. Chapter 1 commences with a brief review of natural and synthetic, proline containing, molecules. Approaches to the synthesis of the proline moiety are described, focusing on previously developed methods for performing the [3+2] dipolar cycloaddition in a chiral manner. The methodology employed in this thesis is subsequently detailed, along with a brief description of the aims of the work. This is followed by a review of α-amino acid synthesis via chiral template technology. The potential application of chiral [3+2] dipolar cycloadditions to such syntheses is introduced. Chapter 2 describes the cycloaddition of carboxylate substituted chiral azomethine ylids with a range of dipolarophiles under both thermal and Lewis acid catalysed conditions. The effect on the stereoselectivity and yield caused by changing the conditions is discussed. Subsequent removal of the chiral template allows the synthesis of some tetra-substituted proline derivatives. Chapter 3 details the intramolecular variant of the cycloaddition. Further functionalisation of the cycloadducts via insertion of alternative chain links and sulfone alkylation was attempted. The Pummerer rearrangement of the related sulfoxide was shown to proceed smoothly and with total regio- and stereocontrol. Application of the methodology to the synthesis of a simple proline derivative and a symmetric pyrrolidine is described. Chapter 4 reports the attempted application of [3+2] dipolar cycloadditions to the synthesis of α-amino acids. The synthesis and subsequent cycloaddition of a new, α-amino acid derived, chiral template is described. Subsequent deprotection of the cycloadducts generated allows the synthesis of some α-phenyl substituted prolines. Unsuccessful attempts to incorporate additional substituents and perform the cycloaddition in an intramolecular manner are described. Chapter 5 contains a description of the techniques employed, together with spectroscopic data for the compounds described in this thesis.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:294328 |
| Date | January 1995 |
| Creators | Lilley, Ian Andrew |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://ora.ox.ac.uk/objects/uuid:64d5745b-e6ef-4a77-8abe-b01f1c627e8f |
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