The Preparation of 2-Isoxazolines from O-Propargylic Hydroxylamines via a Tandem Rearrangement-Cyclisation Reaction

A method for the conversion of O-propargylic hydroxyl­amines into 2-isoxazolines in 60-84% yield is described. For 3alkylpropargyl or 3-arylpropargyl hydroxylamines this was achieved by heating a methanolic solution of the hydrochloride salt in the presence of K2CO3. In the case of the 3-unsubstituted compounds, the hydrochloride salts were first converted to the free bases, which rearranged upon heating in methanol. In one case, the methodology was extended to enable the direct transformation of a O-propargyl phthalimide into a 2-isoxazoline in 65% yield by treatment with methyl hydrazine at room temperature over 19 hours.