Copper-Catalyzed Cross-Couplings Between Carbon-Carbon,Carbon-Heteroatom And Their Applications In The Tandem Synthesis Of Heterocyclic Compounds

Transition metal-catalyzed cross coupling, reaction between electrophilic unsaturated carbon and nucleophilic reagents is one of the most powerful protocols for the generation of C(sp or sp2)-C and C(sp or sp2)-X bonds.Owing to the low cost and low toxicity of copper catalysts, synthesizing various aryl, vinyl and alkynyl functionalized compounds through copper catalyzed coupling reaction not only bears the advantage of atom economics, but also caters to the principle of green chemistry. During the past decade, significant progress has been achieved on the researches of copper-catalyzed coupling reaction. The copper-catalyzed coupling reaction has exhibited promising application potential in industry due to its properties of high efficiency, mild reaction conditions, general reactant tolerance as well as low cost et al.Recently, employing copper-catalyzed coupling transformation to the "one-pot" tandem reaction or stepwise operation for the synthesis of various heterocyclic compounds has been also emerging as a hot topic of this area.The dissertation includes three parts. In the first chapter, the research development and current progress of coupling reactions catalyzed by copper were briefly summarized. In the second chapter, we studied the formation of some C-C, C-O, C-S, C-N bonds under copper catalysis. In the last chapter, the application of copper-catalyzed coupling reactions into the tandem synthesis of 1,4-benzodioxanes was investigated.The second chapter contains three sections. Section one:a new method for the synthesis of dithiocarbamates by CuI-catalyzed coupling reaction. A mild, efficient method for the synthesis of aryl and vinyl dithiocarbamates though the coupling reaction of sodium dithiocarbamates with aryl iodides and vinyl bromides has been developed.. The protocol is applicable to aryl iodides, and even to (Z)-and (E)-vimy1 bromides. Section two:Palladium free synthesis of conjugated enynes by direct olefination of terminal alkynes using vinyl bromides. Without using Pd catalyst, we established a new catalyst system for the coupling of aryl alkynes with vinyl bromide. And a series of conjugated enynes were successfully synthesized by the direct copper-catalyzed coupling process. Compared with previous approach, this method requires simpler and cheaper materials and displayed good efficency. Section three: Mild Cul/β-keto ester-catalyzed coupling reactions of vinyl bromides with phenols, thiophenols and imidazoles. We found that the novel ethyl 2-oxocyclohexanecarboxylate was an efficient and facile ligand for the copper-catalyzed coupling reactions of various N-/O-/S-nucleophilic reagents with vinyl bromides. And we developed the synthetic methodology of synthesizing vinyl ethers, vinyl thioethers and N-vinyl imidazoles. These transformations were achived under milder conditions than known reports. The products were obtained with good yield and excellent stereoselectivity.The third chapter consists of two parts. Part one:Cu2O-catalyzed tandem ring-opening/coupling cyclization process for the synthesis of 1,4-benzodioxanes. Using o-iodide phenols and epoxides as the starting materials, we developed the first tandem synthesis of 1,4-benzaodioxans based on the Cu-catalyzed coupling reaction. This method involves in the use of cheaper materials, simpler work up in contrast to literature synthesis. And the procedure allows the use of both aliphatic and aromatic epoxides. Part two:copper catalyzed tandem process:an efficient approach to 2-substituted-1,4-benzodioxanes. We have developed a new tandem synthetic routes to the novelly decorated 1,4-benzodioxanes. Through the modification on the reactant structure, the problem of producing isomers via the nuleophilic attack to different sites of epoxide has been successfully avoided in the present study. The starting materials are easily accessible and experimental procedures are simple.