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 substituents 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