Study On The Hypervalent Iodine Reagent-mediated Syntheses Of Oxazole And Isoxazole Derivatives

Presented in many biologically active natural products and pharmaceutical agents, the oxazole and isoxazole skeletons are important heterocyclic motifs. Oxazole derivatives and isoxazole derivatives play key roles not only in the SAR study, but also in the organic synthesis. Based on the systematical research, in the first chapter, synthetic strategies and biologic activities of those heterocycles are disclosed detailly to match the need of development of modern medicine and the demand of convenient methods for the synthesis.In the second chapter, a novel phenyliodine diacetate(PIDA)-mediated syntetic method of oxazole derivatives was described detailly. A group of functionalized oxazoles were synthesized in moderate to good yields from enamides via PIDA-mediated intramolecular cyclization. The main advantageous features of the present method include its broad substrate scope and the heavy-metal-free characteristic of the oxidative carbon–oxygen bond formation process. Meanwhile, a possible mechanism for this transformation was proposed based on the experimental data during the reaction condition screening. The successful synthesis of Oxaprozin and its derivatives also showed that this general procedure to access polysubstituted oxazole derivatives was highly desirable.In the third chapter, we described a new application of Fe Cl2 as an inexpensive, nontoxic and efficient catalyst in a clean ring expansion reaction of 2H-azirine derivatives, an intermediate formed through the PIDA-mediated azirination of readily available enaminones. A new one-pot protocol for the synthesis of various substituted isoxazoles from the corresponding enaminones has been further established based on this new reaction, and a possible mechanism for this transformation was proposed based on the the former study of 2H-azirine rearrangement.