Nitrile Oxide [3 + 2] Cycloaddition: Application to the Synthesis of 6-Substituted 3(2H)-Pyridazinones and 6-Substituted 4,5-Dihydro-4-hydroxy-3(2H)-pyridazinones

An efficient method for the preparation of 6-substituted 3(2H)-pyridazinones and 6-substituted 4,5-dihydro-4-hydroxy-3(2H)-pyridazinones starting from 3,5-disubstituted 4,5-dihydroisoxazoles is described. N-O bond cleavage of the isoxazoline ring promoted by molybdenum hexacarbonyl or by catalytic hydrogenation afforded the α-hydroxy γ-keto esters 4a-f which were converted into 6-substituted 4,5-dihydro-4-hydroxy-3(2H)-pyridazinones 5a-f or 6-substituted 3(2H)-pyridazinones 6a-f on treatment with hydrazine hydrate at room temperature or reflux in high yield starting from 4a-f. The flexibility of this protocol has been demonstrated by the synthesis of the C-nucleoside 7 starting from the known β-ribofu-ranosylnitromethane 8. Moreover, an intramolecular version of this methodology has been developed to prepare the known antiulcer tricyclic 3(2H)-pyridazinone 12.