Asymmetric synthesis using chiral vinyl ethers.

Using chiral alcohol precursors, a number of chiral vinyl ethers were prepared by mercuric acetate-catalysed transetherification with butyl vinyl ether. a-Lithiation of (1R)-menthyl vinyl ether was unsuccessful under a variety of conditions. (1S)-(Menthylthio)ethene was prepared from (1S)-menthanethiol but deprotonation was not possible as the thioether was found to decompose rapidly at room temperature. The deprotonation of (R)-phenethyl vinyl ether, (S)-l-(2-naphthyl)-l-ethyl vinyl ether and (S)-l-phenyl-1-butyl vinyl ether and attempted reaction with benzaldehyde yielded none of the a-alkylated adduct but a Wittig rearrangement reaction was seen. The cycloaddition reaction of benzonitrile oxide with a range of chiral vinyl ethers was investigated. The isoxazoline product was isolated as a mixture of two diastereoisomers after flash column chromatography. In most cases the diastereoisomer ratio neared 1:1, but (S)-l-(2-naphthyl)-l-ethyl vinyl ether and 1-phenyl-1-butyl vinyl ether gave a single diastereoisomer of the isoxazoline product, after chromatography, with a variety of nitrile oxides. Conditions have been developed for the removal of the chiral auxiliary but as yet only achiral isoxazolines have been obtained by this method. Attempts at ring deprotonation/alkylation and also the addition of a nucleophile or radical to the isoxazoline C=N bond were hindered by the instability of the isoxazoline adducts. A chiral vinyl pyrrolidinone was also prepared and found to undergo an asymmetric cycloaddition reaction with benzonitrile oxide to yield a single diastereoisomer of the isoxazoline product. The equivalent acrylamide was synthesised and, although this gave a 1:1 mixture of diastereoisomers with both benzonitrile oxide and 2,2-dimethylpropanenitrile oxide, these diastereoisomers could be separated. Removal of the chiral auxiliary yielded hydroxyisoxazolines with an enantiomeric excess of 90-94%. Attempts to investigate the extent of any asymmetric induction in the cycloaddition of nitrile oxides to chiral vinyl sulphoxides were hampered by the instability of the isoxazoline product, which underwent an immediate syn-elimination. In an effort to determine the potential of chloromethyl-(1R)-menthyl ether as a chiral OH protecting group, a series of (1R)-menthoxymethyl ethers were prepared from a variety of racemic and homochiral alcohols. Conditions for deprotection were developed which did not lead to the racemisation of homochiral alcohols. The usefulness of the (1R)-menthoxymethyl ether group as a simple means of measuring enantiomeric excess was demonstrated in a silicon-directed diene synthesis.