Organocatalytic Asymmetric Cyclization Reactions Of α-isothiocyanates In The Construction Of Chiral Scaffords From Important Bioactive Compounds

Isothiocyanates have been widely employed in the synthesis of various kinds of heterocycles due to their diverse reaction activities. Recently, a-isothiocyanates emerged as one kind of the most attractive synthetic reagent in the catalytic asymmetric addition/cyclization reactions. These developed methodologies are employed for the efficient construction of chiral amino acid derivatives as well as spiro compounds. Howerver, all these method are limited in the 1, 2-addtion/cyclization. So, it is of great significance to exploit the new reaction using α-isothiocyanates for the construction of more challenging synthetic targets.This dissertation focuses on the development of new methodology using α-isothiocyanates. In our work, we have realized the a-isothiocyanates participated 1, 4-addtion/cyclization and self-cyclization/ring-opening reaction. By using these new methods, a variety of chiral spirooxindoles as well as β-amino thiooxazoles was efficiently constructed.The dissertation includes five chapters. The first chapter reviewed the research developments in both isothiocynates participated cyclization reactions and the recently developed methods for the asymmetric construction of spirooxindole frameworks. In chapter 2, we firstly disclosed the catalytic asymmetric 1,4-addtion of α-isothiocyanato imides. This work not only expands the reaction scope of α-isothiocyanates, but also provides a new method for the construction of densely functionalized spirooxindoles with three contiguous stereogenic centers. In chapter 3, a highly efficient enantioselective Michael addition/cyclization reaction of isothiocyanato oxindoles has been developed. This process solved the challenging problem of the catalytic asymmetric synthesis of 3,2’-pyrrolidinyl spirooxindole motif, and thereby offers an unprecedented platform for their medicinal chemistry research. In chapter 4, we focus our study on the active intermediates of a-isothiocyanato imides in the catalysis system, and developed the catalytic asymmetric ring-opening reaction to aziridines by trapping the 2-thiooxazole intermediate. This method provides an efficient way for the synthesis of chiral (3-aminothiooxazole compounds which can be used as precursors of biological active compounds as well as N, S-ligands. The last chapter is about the brief summary of the our works and the prospect in this research field.