Studies On Asymmetric Cross Dehydrogenative Coupling Reaction

Functionalized nitrogen-containing heterocycles constitute a widespread structural motif in biologically active moleculars and an invaluable template for chiral auxiliaries in asymmetric synthesis. The cross dehydrogenative coupling of a C-H bonds adjacent to a nitrogen atom with other C-H bonds provides a concise and efficient way to synthesis of these privileged heterocycles. Today, the development of this transformation into an enantioselective process still remains a great challenge. This thesis is about the development of novel methods, from transition-metal to metal-free process, namely organocatalyst, to introduce functionalities asymmetrically to a-position of amines for the synthesis of the functionalized nitrogen-containing compounds.This dissertation includes seven chapters. The first chapter reviewed the recent developments in asymmetric cross coupling reactions. In the second section, we described a Box/copper-catalyzed asymmetric dehydrogenative coupling between glycine esters and β-kcetoesters for the synthesis of a-alkyl-α-amino acids. The third part is the research of the enantioselective metal/organo-catalyzed a-olefination of tertiary amines with unsaturated carbonyl compounds, which allowed a rapid way to construction of diverse optically active Cl-alkene tetrahydroisoquinoline derivatives. The fourth part is about transition-metal-free catalytic asymmetric cross dehydrogenative coupling of tertiary amines with cycle ketones for the construction of a Csp3-CSp3 bond under mild conditions. This method provided an efficient access to Cl-alkylated tetrahydroisoquinolines. In the fifth chapter, the metal-free catalytic intramolecular oxidative coupling of tertiary amines for the construction of ring-fused tetrahydroquino lines was disclosed. In the following part, described an organocatalytic tandem Michael/cyclization reaction for enantioselective synthesis of functionalized pyranocoumarins and 2-amino-4H-chromenes, and the preliminary biological study of these compounds shows efficient antibacterial activity. The last section is the summary of each chapter in this thesis.This dissertation is focused on catalytic asymmetric cross dehydrogenative coupling of secondary and tertiary amines for building of a-alkyl-a-amino acids, C1-alkene, C1-alkylated and ring-fused tetrahydroisoquinolines. The last chapter is about the synthesis and the antibacterial activity study of chiral pyranocoumarins and 2-amino-4H-chromenes.