Investigation of a new substrate directed aza-Claisen rearrangement for natural product synthesis

Jamieson, Andrew G (2006) Investigation of a new substrate directed aza-Claisen rearrangement for natural product synthesis. PhD thesis, University of Glasgow.

Abstract

A novel substrate directed, palladium(II)-catalyst aza-Claisen rearrangement has been developed. Aza-Claisen rearrangement of a series of delta-ether substituted allylic trichloroacetimidates demonstrated that the oxygen atom in this position can effectively direct facial coordination of the palladium(II)-catalyst, with the MOM-ether substrate giving the most selective rearrangement reaction. An optimisation study was carried out using different catalysts and reaction conditions. The results from this study showed that bis(acetonitrile)palladium(II) chloride catalyst and non-coordinating solvents such as toluene give the most selective rearrangement resulting in the isolation of the anti-compound in up to 88% diastereomeric excess. This methodology was used as the key step in the novel diastereoselective synthesis of beta-hydroxy alpha-amino acids from enantiopure alpha-hydroxy acids. During the rearrangement step, a competing [1,3] pathway catalysed by palladium(O) was suppressed using p-benzoquinone as an in-situ oxidant in the reaction mixture. A series of compounds based on the structure of the piperidine alkaloid (+)-alpha-conhydrine were synthesised using this newly developed ether-directed, palladium(II)-catalysed aza-Claisen rearrangement and a ring closing metathesis reaction as the key steps.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: Andrew Sutherland
• Keywords: Organic chemistry
• Date of Award: 2006
• Depositing User: Enlighten Team
• Unique ID: glathesis:2006-74005
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 23 Sep 2019 15:33
• Last Modified: 23 Sep 2019 15:33
• URI: https://theses.gla.ac.uk/id/eprint/74005