Study On Novel Synthesis Of3-Hydroxy-2-oxindoles And Spirooxindoles Mediated By PIFA

3-Hydroxy-2-oxindole is an important motif found in many natural products andpharmaceutical compounds with a wide spectrum of biological activities. Hence it isof vital importance to develop novel approaches to synthesize such compound.Spirooxindole is also a fundamental class of compound which plays an indispensablerole in the biological and pharmaceutical industry. This thesis mainly introduces theresearch of the systhesis of N-subsitituted-3-hydroxy-2-oxindoles and spirooxindolesincluding the following aspects:1. Based on the research results from our group, an approach to synthesize indolevia constructing C-C bond by the connection of C（sp²） in the benzene ring and C（sp³）in the side chain followed by hydroxylation was developed. Therefore, we designedvarious anilides as substrates for further study via the condensation between differentN-substituted anilines and monoethyl molonate or other acids.2. Mediated by hypervalent iodine reagent, namely, phenyliodinebis（trifluoroacetate）（PIFA）, these anilides mentioned above underwent intramolecularcyclizaton to afford oxindole nucleus and hydroxyl group was also added at the3position to generate3-hydroxy-2-oxindole derivatives at room temperature. TheN-substituents could be methyl group, benzyl group or aryl group, and the benzenering could be substituted by weak electron-withdrawing groups or electron-donatinggroups. Substrates with strong electron-withdrawing groups failed to deliver thisstructure. Sixteen3-hydroxy-2-oxindoles have been prepared through this method.3. During the research, we discovered3-oxo-butananilide derivatives mediatedby PIFA failed to undergo intramolecular cyclization, but only a hydroxyl group wasintroduced. Then in the presence of H₂SO₄,3-hydroxyquinolin-2（1H）-one could beprepared in one pot, which is also a new method to prepare these compounds. Five3-hydroxyquinolin-2（1H）-ones were successfully prepared throuth this method.4. Under the identical reaction conditions, N¹,N³-diphenylmalonamidederivatives as substrates were conveniently converted to the spirooxindoles. It had nolimitation whether the benzene ring was substituted by electron-withdrawing orelectron-donating groups. Eight spirooxindole derivatives were generated throuth thismethod.5. Based on the experimental results, a plausible mechanism was proposed forthe PIFA-mediated tandem oxidation process. Explanations were given on the substrates where intramolecular cyclization could not occur.