Reaction of ketoximes with methyl propiolate afforded geometrical isomers of the methyl 3-(hydroxyimino)propanoates 4 and of the O-vinyl oximes 5 as well as the 2-isoxazoline 6. With dimethyl penta-2,3-diendioate 8c reaction progressed via an O-alkylation to give the O-oxime ethers 9, only in the case of cyclopentanone oxime was the spirocyclic dihydroazepinol 11 also obtained, its identity has been confirmed by an X-ray structure determination.

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 R-3 and the space filling capacity of the substituents R-1, R-2 and R-4. When the olefinic centre is electron poor (R-3 = 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 (R-3 = Ph) the primary product of reaction is the corresponding oxime which on thermal activation converts to the tricyclic isoxazoloquinolinones.

Synthesis of the title ring system by a sequential intermolecular nucleophilic displacement and intramolecular 'conjugate' addition has been achieved both as a one pot and as a stepwise procedure; an X-ray structure determination has been carried out to distinguish between the possible isomeric structures 8c-I and 8c-II.

The aldoximes 1 in the presence of electron poor olefins react to form either the 5,6,7-tricyclic isoxazolobenzodiazepinone 3 or the 5,6,6-tricyclic isoxazoloquinolinone 5 ring skeleton, In each case the ring system formed depends on the relative electrophilicity of the added and internal olefin, The oximes 1a,b,c react with N-methylmaleimide, methyl acrylate or phenyl vinyl sulfone to afford the corresponding regioisomeric isoxazolobenzodiazepinones by a tandem intramolecular dipole formation-intermolecular cycloaddition sequence, With the more electrophilic olefin, methyl vinyl ketone, intermolecular nitrone generation precedes intramolecular cycloaddition and the isoxazoloquinolinone skeleton results and for each oxime reaction proceeds smoothly in a regio-and stereo-specific manner, Steric control of chemoreactivity is observed with the ring or chain substituted aldoximes 1d,e,f. These oximes react in the presence of phenyl vinyl sulfone to give the isoxrazolobenzodiazepines 15 and 16 together with varying quantities of the N-unsubstituted isoxazoloquinolines 14, The latter arise via an oxime-nitrone-cycloaddition sequence, in each case the cycloaddition proceeds in a regio-and stereo-specific manner, The oximes 1d,e,f react with methyl vinyl ketone to give single regio-and stereo-isomers of the N-unsubstituted and -substituted isoxazoloquinolinones 14 and 17, The high degree of chemo-, regio-and stereoselectivity with which the one-pot reaction of the oximes 1 with electron poor olefins proceeds represents a convenient method for the construction of the title tricyclic molecular frameworks.

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