Highly Stereoselective Synthesis Of Spirooxindoles Via Organocascade Reactions

The spirooxindoles,which occur in many alkaloid natural products, have drawn tremendous interest of researchers in the area of organic synthetic chemistry and medicinal chemistry worldwide because of a wide range of important biological and pharmacological activities. cascade reactions have been widely used in the synthesis of spirooxindoles by virtue of their high efficiency and easy operating. In this dissertation, our attention mainly focuses on the construction of structurally diverse spirooxindoles via organocascade reactions. The whole work is mainly composed of following three parts:Part I: Highly diastereoselective synthesis of spiro-triazolidine oxindoles containing N,N?bicyclic heterocycles via 1, 3-dipolar cycloaddition reactions. Initially, We chose N,N'-cyclic azomethine imines and isatin imines as substrates, and systematically optimized for this reaction conditions by screening catalysts, tempratures, solvents, catalyst loading. Subsequently, under the optimal reaction conditions, we extended the reaction scope. The relative configuration of spiro-triazolidine oxindoles was determined by the single crystal X-ray analysis. Then reaction mechanism was hypothesized to account for the stereoselective formation of spiro-triazolidine oxindoles by relative configuration of spiro-triazolidine oxindoles and DFT calculations locating the concerted transition state.Part II: In the presence of inorganic base, the desired spiro-imidazolidine oxindoles were obtained in excellent chemical yield and dr value by means of the diastereoselective [3 + 2] cycloadditions of N-acylhydrazinederived imines with 3-isothiocyanato oxindoles. The relative configuration of spiro-imidazolidine oxindoles was determined by the single crystal X-ray analysis, then we proposed mechanism for the [3 + 2] cycloadditions.Part III: Highly enantioselective synthesis of spiro-pyran oxindoles via organocatalytic cascade reactions. In the presence of organocatalyst, the developed organocatalytic three-component cascade reaction of isatins, malononitrile, and 2-hydroxynaphthalenes readily proceeded to furnish chiral spiro-pyran oxindoles in excellent chemical yields and high enantioselectivities. A single crystal of spiro-pyran oxindoles was obtained, and its absolute configuration was determined to be R by X-ray crystal structure analysis. Moreover, a reaction mechanism is proposed that accounts for the stereocontrolled formation of the chiral spiro-pyran oxindoles.