Synthetic and mechanistic aspects of dioxirane chemistry

The range and understanding of oxidations by dioxiranes has been extended. Epoxidation of cholesterol and 3β-acetoxycholest-5-ene with a range of dioxiranes generated in situ, affords the 5α,6α and 5β,6β-cholesteryl epoxides in the ratio 1:1. This result differs significantly from peroxyacid methods where α:β 4:1 is expected. 4,4-dimethylcholest-5-enes were not epoxidised and instead a preferred allylic oxidation to give the 7-ketone was observed. The results have allowed mechanistic implications to be proposed in favour of a spiro transition state for the epoxidation of alkenes. Oxidation of estradiol derivatives with dimethyldioxirane gave selective benzylic oxidation to form 9α-hydroxy compounds in good yield. The conversion of alcohols to ketones has been investigated. Oxidation of 18O cholestan-3β-01 by dimethyldioxirane has shown that there is a 40% loss in 18O label from the alcohol. This result suggests that a mechanism involving oxygen atom insertion from the dioxirane into the C-H bond is occurring. Experiments have also shown that axial alcohols are oxidised faster than equatorial alcohols. A series of benzyl ethers has been oxidised by dimethyldioxirane. Aromatic benzyl ethers afford the phenol whilst, 3-benzyloxycholestane yields cholestan-3-one via cholestan-3β-ol. Benzaldehyde dimethylacetal and phenyl acetaldehyde dimethylacetal gave methyl benzoate and methyl phenyl acetate respectively. Epoxides derived from a series of chromenes have been obtained in excellent yields using dimethyldioxirane. Approaches to a method for asymmetric epoxidation of alkenes using dioxiranes derived from chiral ketones have been investigated. However, only a low level of enantiomeric excess (ca 11 %) has been achieved. Acetophenone and benzophenone derived fluoro-ketones have also been used and their potential as reactive dioxirane intermediates assessed. Preliminary work on the application of dioxiranes to oxidation of β-lactams has been investigated