The synthesis of a novel spiro-oxazolidin-2-one chiral auxiliary from both enantiomers of the common terpene camphene is described. The compound is formed <I>via</I> nitrene insertion and its structure has been determined by both NMR spectroscopy and X-ray diffraction studies. Evaluation of the functionalisation conditions for this hindered oxazolidin-2-one have been carried out and it has been observed that zinc salts give superior yields of <I>N</I>-acyl products compared to the use of the orthodox lithium or halomagnesium salts. It has been demonstrated that using suitable conditions the auxiliary is capable of inducing high degrees of stereoselectivity in a variety of enolate reactions including alkylation, acylation and aldol condensation. Unsaturated acyl derivatives undergo Diels-Alder cycloaddition with cyclopentadiene in the presence of diethylaluminium chloride to give adducts with very high diastereomeric excess. Michael additions of aluminium reagents to these acyl derivatives also give high diastereomeric excesses where the possibility of formation of a cationic intermediate exists. When such intermediates cannot be formed, in particular addition of trialkyl aluminium reagents, very low diastereomeric excesses are observed. 1,4-Conjugate addition of magnesium reagents is dependent on the presence of copper catalysts but the reactions proceed with high stereoselectivity and the intermediate enolates may be readily alkylated with equal specificity. In many cases the so formed adducts have been cleaved to give the newly created chiral fragments in high optical purity and chemical yield with almost complete recovery of the auxiliary (>90%). The application of a combination of stereoselective 1,4 conjugate addition and aldol condensation reactions has been applied to the synthesis of a number of substituted β-carboxy-γ-lactones (paraconic acids). The stereochemistry of these target molecules has been readily created with a high degree of specificity in very good chemical yield. In one attempted synthesis use of a surprisingly stereoselective lithium enolate aldol condensation is described. The origins of this selectivity has been proposed after considering the selectivities of a number of different substrates. However removal of the chiral product fragment from the auxiliary leaving both intact has been found to be highly dependent on both the functionality and stereochemistry of the adduct. Further applications of the auxiliary to short natural product synthesis and the potential of these routes is also briefly described.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:662935 |
| Date | January 1997 |
| Creators | Thorburn, Paul |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/13130 |
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