Synthetic Methodologic Studies On Isoquinolines And Isoindolinones Catalyzed By Ir(Ⅲ) And Iodine

Nitrogen-based heterocycles are kinds of key bioactive organic chemicals, they are common important structures of various natural products. Much attention are paid to isoquinolines and isoindolinones beause of their excellent biological activities. However the classical approaches for the synthesis of the two compounds which have harsh reaction conditions, low yields, low selectivity don't meet the needs of the green chemistry. The development of more economic, concise, efficient synthesis method is requisite and challenging.In this dissertation, nitrogen-based heterocycles such as isoquinolines and isoindolinones were preparated by Ir-catalyzed cyclization of functionalized alkynes and alkenes, this represents a hot process in synthetic, particularly in pharmaceutical chemistry.In this dissertation, we have achieved isoquinolines from nitrone alkynes through the internal redox cyclization of nitrone-functionalized terminal alkynes mediated by a simple iridium(III) complex(IrCp*Cl2). Firstly, iridium azomethine complexes have been isolated from nitrone-alkynes and 0.5 stoichiometric IrCp*Cl2 in good yields. Due to the lability of the complex, heating the complex with MeI readily afford the ionic complex. Secondly, catalytic cyclization of nitrone alkynes with 1mol% IrCp*Cl2 afford azomethine ylides in high yields. Furthermore, the nucleophilicity of the oxygen atom of azomethines were revealed by the reaction with HCl·Et2O or MeI, wherein protonation and methylation products were isolated, respectively, in high yields. Azomethine ylides also can undergo an intermolecular [3+2] dipolar addition reaction with activated alkynes or alkenes to give different stereoselective isoquinolines. The potential reaction mechanism has been probed by the X-ray crystallography and kinetics of the reaction. A new efficient approach for synthesize isoquinolines has been developed. This strategy should find broad applications in the synthesis of related bioactive organic heterocyclic molecules.In this dissertation, we have achieved iodinated isoindolinones from nitrone alkynes through the I2-mediated cyclization with a process of the intramolecular oxygen transfer. We also have achieved diketones from sulfoxide alkynes through the I2-mediated cyclization via an addition-elimination process. We give a plausible mechanism due to the related experiment. A new efficient approach for synthesize isoindolinones or diketones has been developed. This method could quickly proceed in excellent yields under mild conditions.