Studies On Organocatalytic Domino Cyclization And Methodology For The Synthesis Of Oxindole Skeleton

In the first chapter, we have reviewed the recent studies on organocatalytic domino cyclizations. Recently, organocatalytic domino reactions have quickly become a powerful and efficient tool in organic chemistry. More and more organocatalytic multicomponent domino reactions have been utilized for the efficient and stereoselective construction of complex molecules from simple precursors in a single process, and they often proceed with excellent stereoselectivities and are environmentally friendly because the use of toxic metals are avoided. Asymmetric organocatalysts mainly consist of chiral amines and chiral Brφnsted acids. Organocatalytic domino reactions catalyzed by amines, especially secondary amines, are widespread, as secondary amines are capable of both enamine and iminium catalysis. Most of the chiral amines-catalyzed domino reactions are based on iminium-enamine activation, enamine- enamine activation and enamine- iminium activation. In Brφnsted acids-catalyzed domino reactions, the activation of the substrate relies on the partial protonation or the formation of a strictly directed hydrogen bond by the catalyst. The interaction between the catalyst and the substrate is noncovalent, and the chiral ion pair is the intrinsic activated species. Chiral thiourea-based derivatives and phosphoric acid derivatives are effective Brφnsted acid organocatalysts. We have developed a facile and efficient synthesis of 1,3-diaryl-5-spirohexahydropyrimidines via a one-pot Mannich-type condensation of anilines, formaldehyde and cyclohexanones catalyzed by proline. In this one-pot three-component reaction, six molecules of reactants are involved and six new covalent bonds are generated. Bicyclic products are obtained from the starting materials in one pot using readily available starting materials and catalysts.In the second chapter, we have reviewed methodology for the synthesis of oxindole skeleton. Oxindoles are common and important substructures in natural products and biologically active molecules. Numerous methods have been reported for the synthesis of oxindoles, including cyclization of o-aminophenylacetic acids andα-halo orα-ahydroxy acetanilides, the derivatization of isatin and indoles, radical cyclizations, palladiumcatalyzed Heck reactions, domino Heck/cyanation reactions, cyanoamidation reactions, Coupling of Csp2 and Csp3, Pummerer reaction, and cyclization of propiolanilides and 2-(alkynyl)aryl isocyanates. We have developed two reliable and operationally simple protocols to synthesize functionalized oxindoles via palladium-Catalyzed C-H functionalization and iodonium-mediated electrophilic cyclization of simpleα,β-unsaturated amides.