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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:571861 |
| Date | January 2012 |
| Creators | Fairhurst, Nathan W. G. |
| Contributors | Carbery, David |
| Publisher | University of Bath |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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