The Study Of Domino Reactions Containing 3-phenacylideneoxindoles

In recent years, chemistry of isatin has been received wide concerns along with the rapid development of multicomponent reactions. Isatin and its derivatives are the privileged structural scaffolds of many naturally occurring substances and the synthetic pharmaceuticals. They have showed a wide variety of biological activities such as anti-tumor, anti-bacterial and so on. 3-Phenacylideneoxindoles, which can be easily derived from condensation of isatins with acetophenones, have the structure of α, β-unsaturated ketones and were widely used as synthetic blocks for the synthesis of diverse spirooxindole frameworks. In this thesis, we successfully developed several domino reactions by using 3-phenacylideneoxindoles as one of main substrate and synthesized several kinds of spirooxindole systems. The advantages of these reactions included using readily available starting material, mild reaction conditions, simple operation and good yields, which provided convenient and practical synthetic procedures for the complex spirocompounds.1. A simple protocol for the construction of novel dispirocyclopentanebisoxindoles is accomplished by the base promoted domino reactions between two molecules of 3-phenacylideneoxindoles with the participation of solvents, alcohol, or other added nucleophiles such as amines or thiophenols. Significantly, this domino reaction results in the complex dispiro compounds with high yields and diastereoselectivity, which would allow construction of dispirocyclopentanebisoxindole with four and five diastereoisomeric centers using simple materials. All products were characterized by IR,1H NMR,13C NMR, HRMS spectroscopy. The single crystal structures of six products were determined by X-ray diffraction method.2. We systematically investigated the domino reactions of 3-phenacylidene-oxindoles with a series of vinyl malononitriles and successfully developed an efficient protocol for the synthesis of novel functionalized spirocyclic oxindoles. It is interesting to find out that the base appears to be a crucial factor for this reaction, and the reaction mechanism is also rationally proposed on the basis of capture of the reaction intermediates. All products were characterized by IR,1H NMR, 13C NMR, HRMS spectroscopy. The single crystal structures of fourteen products were determined by X-ray diffraction method.3. The multicomponent reactions of imines, dialkyl acetylenedicarboxylate and 3-phenacylideneoxindole afforded functionalized spiro[indoline-3,2’-pyridine] in good yields. The reaction mechanism involved the sequential formation of Huisgen 1,4-dipole and dipolar cycloaddition. This domino reaction has the advantages of using readily available raw material, mild reaction condition and high yields. This reaction provided convenient synthetic procedure construction of complex spiro compounds and high molecular diversity. All products were characterized by IR,1H NMR,13C NMR, HRMS spectroscopy. The single crystal structures of six products were determined by X-ray diffraction method.