Regioselective Synthesis of Isoxazoles by Hypervalent Iodine(III) Reagent Mediated Oxidative Cycloaddition

University of Minnesota M.S. thesis. August 2019. Major: Chemistry. Advisor: Viktor Zhdankin. 1 computer file (PDF); ix, 106 pages.Isoxazole is a five membered heterocyclic compound containing oxygen and nitrogen atoms in the 1,2 positions. Isoxazole rings are found in natural products, such as ibotenic acid and muscimol. The isoxazole structure is incorporated in a variety of pharmaceutical agents. Substitution on different positions on the nucleus of the isoxazole results in various pharmacological effects. Specifically, isoxazole compounds are used in various types of pharmaceutical compounds to treat bacterial infections and pain relief. Oxidative cycloaddition of aldoximes with unsaturated substrates provides an efficient approach to the formation of heterocyclic compounds. More specifically, various isoxazoles can be easily prepared by the oxidative cycloaddition of aldoximes with unsaturated substrates in the presence of hypervalent iodine(III) reagents. Oxidation of aldoximes by hypervalent iodine(III) compounds produces nitrile oxides which further react with respective unsaturated substrates through a 1,3-dipolar cycloaddition reaction resulting in various isoxazole products. This technique is an efficient process that utilizes green chemistry. Here, we report an efficient synthetic approach for preparation of various regioselective 3,4-substituted isoxazoles and 3,4,5-substituted isoxazoles using [hydroxy(tosyloxy)iodo]benzene, commonly known as Koser’s reagent. To our knowledge, this is the first time the 3,4-substituted isoxazole has been prepared. The oxidative cycloaddition proceeds at room temperature resulting in moderate to high yields. Structures of several isoxazole derivatives were established by X-ray crystallography. These isoxazole derivatives are stable compounds that have the potential to be useful for biologically active molecules and pharmaceutical reagents