Steric control of reactivity: Formation of oximes, benzodiazepinone N-oxides and isoxazoloquinolinones

Reaction of the alkenyl carbonyl compounds 1 with hydroxylamine can lead to the formation of the oximes 2, the benzodiazepinone N-oxides 3 or the isoxazoloquinolinones 5. The product(s) of reaction are shown to depend on the electronic nature of the terminal olefinic substituent R³ and the space filling capacity of the substituants R¹, R² and R⁴. When the olefinic centre is electron poor (R³ = CO₂Et) ketocarbonyls convert exclusively to bicyclic nitrones 3 whereas aldehydes are more sensitive to subtle changes in skeletal structure and give rise to oximes 2, tricycles 5 or mixtures of both. For aldehyde and ketone substrates when the olefinic centre carries an aryl substituent (R³ = Ph) the primary product of reaction is the corresponding oxime which on thermal activation converts to the tricyclic isoxazoloquinolinones.