Organocatalytic Asymmetric Nucleophilic Addition Reactions Of Isatins And Isatin-derived Ketimines

3,3-Disubstituted oxindoles are a class of common structures that are broadly existed in nature.In particular,3-substituted-3-hydroxyoxindoles and 3-substituted-3-aminoxindoles are core skeletons in many natural products and pharmaceutical compounds which show promising biological and medicinal activities.Consequently,considerable efforts have been devoted to exploring efficient and direct protocols to synthesize such molecules,and after several years' development,a variety of asymmetric methodologies have been successfully established.Among them,the catalyst promoted direct and stereoselective nucleophlic addition of nucleophiles to isatins and isatin-derived ketimines is one of the most popular methods due to the diversity of catalysts and nucleophiles and readily availability of isatins and their derivatives.In this thesis,we mainly focus on the small molecules organocatalyzed asymmetric nucleophlic addition of carbonyl compounds to isatins and their derivatives to synthesize various potentially biological active 3,3-disubstituted oxindoles.There are three chapters in this thesis.Chapter 1 first briefly introduced some representative natural products and medicinal compounds containing 3-substituted-3-hydroxyoxindole and 3-substituted-3-aminoxindole moieties and generally summarized the methods to construct the quaternary stereogenic center,then intensively discussed the recent development of catalytic asymmetric synthesis of those molecules via nucleophlic addition of nucleophiles to isatins and their derivatives.Chapter 2 mainly investigated an N-heterocyclic carbene catalyzed chemoselective intermolecular cross-benzoin reaction of aldehydes with isatins,the employment of an electron-withdrawing carbene catalyst successfully suppressed the formation of the undesired hydroacylation products and afforded 3-substituted-3-hydroxyoxindoles with moderate to good yields and good to excellent enantioselectivitiesChapter 3 documented a cinchona alkaloid derived bifunctional catalyst promoted formal asymmetric Mannich reaction of azlactones with isatin derived ketimines,providing 3-substituted-3-aminoxindole products bearing two vicinal quaternary stereogenic centers with moderate to good yields,good to excellent diastereoselectivities and enantioselectivities.