Efficient synthesis of 3,5-functionalized isoxazoles and isoxazolines via 1,3-dipolar cycloaddition reactions of 1-propargyl- and 1-allylbenzotriazoles

Abstract

3-Aryl-5-(benzotriazol-1-ylmethyl)- 10a-f and 3-p-methoxyphenyl-5-(α-benzotriazol-1-yl-α-ethoxymethyl)-isoxazol e (13) were prepared in high yields by 1,3-dipolar cycloadditions of 1-propargylbenzotriazole (5) and (α-ethoxypropargyl)benzotriazole (8), respectively, with nitrile oxides 3a-f (prepared in situ from benzohydroximoyl chlorides 2a-f). The benzotriazol-1-ylmethyl moiety was further elaborated by sequential lithiation and reaction with aldehydes, alkyl halides and Michael acceptors. Similar 1,3-cycloadditions using 1-allylbenzotriazole (6) and 1-(α-ethoxyallyl)benzotriazole (7) afforded 3,5-substituted isoxazolines 11b,f and 12 in excellent yields.