Studies On Copper-Catalyzed Synthesis Of 2-Oxoindolin-3-Ylidene Derivatives And Its Reaction With β-Ketothioamide

2-Spiro oxindole derivatives are a class of indole derivatives having potential biological and medicinal activity.3-methylene-2-oxindole is an important class of intermediates. Frequently, the methods for synthesizing the 3-methylene-2-oxindole have some defects such as complex operation, bw atomic economy and narrow substrate range. This paper has established a kind of method for synthesis of 3-methylene-2-oxindole method with isatin and ethyl isocyanoacetate as synthons.In the first chapter, we generally described the extensive applications of isatin derivatives in organic synthesis and reactions of isocyanoacetate derivatives with aldehydes or ketones; different protocols of preparing 3-ylidene-2-oxoindolin derivatives;β-Ketothioamides are versatile building blocks for the rapid construction of various heterocyclic compounds.In the second chapter, a method was established to synthesize multi-substituted 3-ylidene-2-oxoindolin derivatives, prepared starting with isatin and isocyanoacetate, which had not been reported in literatures. By comparing the effects on reactions of different kinds of catalyst, ligand, solvent and temperature, we found the optimal condition was CuI (10 mol%) as catalyst, phenanthroline (10 mol%) as ligand at 110 ℃ in toluene. A possible reaction mechanism involved in 1,3-dipole/retro-1, 3-dipole reactions. First 2-oxoindolin-spiro-oxazoline was obtained during the reaction of isatin and isocyanoacetate through 1,3-dipole reactions, then the ring-opening of oxazoline through retro-1,3-dipole reactions, followed by the removal of isocyanic acid, generated the target product 3-ylidene-2-oxoindolin 3.In chapter three, we explored an approach to synthesize a new kind of 3-pyrrolidin-2-oxindole derivatives 6 via 3-methylene-2-oxindole and/β-ketothioamide. Piperidine as a catalyst at room temperrature was found the optimal condition.The structures of all the new compounds were characterized by IR, 1H NMR,13C NMR, and HRMS. Furthermore, single crystals of compound 3h and 6a were cultured and their molecular structures were determined.