Norbomane, hydroxylation

Early studies with a purified and reconstituted rabbit P450, CYP2B4 (earlier name P450 LM2) on the hydroxylation of the hydrocarbon, norbomane, found that the reaction proceeded to yield a 3.4 1 mixture of exo-endo norborneols (4). Further, hydroxylation of exo-2,3,5,6-tetradeuteronorbornane was found to proceed with a large deuterium isotope effect (11.5 0.5) and a significant amount of epimerization in forming the endo and exo metabolites (Fig. 4.3). 

Two new reactive, very powerful organic peroxides, dimethyldioxirane and methyl(trifluoromethyl)dioxirane (4), have been introduced.81-83 The latter is more reactive and can be used more conveniently.84 85 Acyclic alkanes give a mixture of isomeric ketones on oxidation with methyl(trifluoromethyl)dioxirane,84,85 while cyclohexanone is the sole product in the oxidation of cyclohexane (99% selectivity at 98% conversion).85 With the exception of norbomane, which undergoes oxidation at the secondary C-2 position, highly selective tertiary hydroxylations can be carried out with regioselectivities in the same order of magnitude as in oxidations by peracids.85-87 A similar mild and selective tertiary hydroxylation by perfluorodialkyloxaziridines was also reported.88 Oxidation with dioxiranes is highly stereoselective 85... 

There has been much discussion in the field about the oxygen transfer process 6 —> 7 —> 8. The oxygen rebound mechanism in Scheme 1.1 is consistent with the stereochemical, regiochemical, and allylic scrambling results observed in the oxidation of norbomane, camphor, and cyclohexene by cytochrome P450. The hydroxylation of... 

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