Abstract:

Isoxazoles are very important organic compounds, and many natural products and drugs contain the five-membered heterocycle moiety. A variety of synthetic methods has been known for preparation of iso-xazoles, of which the cycloaddition of nitrile oxides with alkynes is the most direct. In the reported procedures, the yields of isoxazoles are often quite low, side reactions result in impurities and both regioisomers are often obtained. Recently, the catalytic utilization of hypervalent iodine reagents is increasing in importance, with the growing interest in the development of environmentally benign synthetic transformations. In order to extend the scope of catalytic use of hypervalent iodine reagents in organic synthesis, we investigated the new method for preparation of isoxazoles using iodobenzene as catalyst and a novel catalytic method for synthesis of 3,5-disubstituted isoxazoles was reported. Terminal alkynes were mixed and stirred with oximes, m-chloroperbenzoic acid and a catalytic amount of iodobenzene in 2,2,2-trifluoroethanol at room temperature for several hours, a [3+2] cycloaddition was easily be carried out, and after establishing optimal conditions, a series of 3,5-disubstituted isoxazoles was obtained in good yields. The possible mechanism for the cycloaddition was suggested, which included iodobenzene was first oxidized by m-chloroperbenzoic acid into the hypervalent iodine intermediate, then it transformed oximes to nitrile oxides in situ, following a cycloaddition of the nitrile oxides with alkynes to form isoxazoles. The method has some advantages such as mild reaction conditions, simple procedure and good yields.

Key words: Isoxazole, Hypervalent iodine intermediate, Catalytic oxidation, [3+2]Cycloaddition