Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.571861
Title: The Ireland-Claisen rearrangement of 3-alkoxypropenol amino esters as an entry to sphingolipid amino acid natural products
Author: Fairhurst, Nathan W. G.
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 2012
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Abstract:
The Ireland-Claisen rearrangement is a powerful synthetic tool which allows predictable diasterocontrol and chirality transfer in the synthesis of γ,δ-unsaturated carboxylic acids. Previous work within the Carbery group has developed a novel protocol for the synthesis of β-alkoxy- and aryloxy-α-amino acids. Chapter 2 covers the initial volume of work on developing this methodology further to allow the synthesis of sterically congested α-quaternary carbon centres in β-alkyoxy- and aryloxy-α-amino acids. Individual substrate optimisation allowed improvement of both the yields and diastereoselectivity of this rearrangement, along with the isolation of a key degradation product. A series of heteroproline-based rearrangements laid the groundwork for remote chirality transfer within this Ireland-Claisen rearrangement. The principle of self-regeneration of stereocentres is applied in an Ireland-Claisen context in Chapter 3. Showing exceptional levels of remote stereocontrol the rearrangement is shown to be general, offering almost exclusively diastereoselectivities of >99:1. Allylic enol ether amino esters saw yields of 47 – 83% and provided functional handles allowing for further synthetic manipulations. Carbon substituted allyl amino esters allowed facile access into β-hydroxy-α-amino acid derivatives of proteinogenic amino acids leucine and isoleucine (amongst others) with excellent selectivity. The synthesis of both enantiomers of mycestericin G in Chapter 4 highlights the synthetic utility of this methodology, in addition to allowing a revision of absolute configuration of this natural product. The synthesis of a mycestericin G analogue, derived from threonine, is also presented. Finally, Chapter 5 exploits these rearrangement products as chiral diene ligands in rhodium-catalysed conjugate addition reactions. Both ligand and reaction condition optimisation led to a range of aryl boronic acids used in the 1,4-addition to 2-cyclohexenone with yields of 24 – 100% and enantioselectivities of 74 – 93% observed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.571861  DOI: Not available
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