Iodocyclization of hydroxylamine derivatives based on the control of oxidative aromatization leading to 2,5-dihydroisoxazoles and isoxazoles
An efficient method for the synthesis of 2,5-dihydroisoxazoles and isoxazoles using iodocyclization of N-alkoxycarbonyl O-propargylic hydroxylamines has been developed. 2,5-Dihydro-4-iodoisoxazole underwent the cross-coupling reactions without aromatization to afford polyfunctionalized 2,5-dihydroisoxazoles. This process was applied to the preparation of valdecoxib and its 2,5-dihydro-derivative.
The entitled alcohols are obtained by reaction of cuprous reagents with α-acetylenic epoxides bearing a phtalimido group in α' position, followed by hydrazinolysis.They show an inhibitory effect on the growth of certain transformed cells in tissue culture