Design, Synthesis And Application Of Novel Chiral Squaramide Catalysts In Asymmetric Catalytic Reaction

In recent years, much attention has been paid to hydrogen bonding donor chiral squaramide catalysts owing to their unique structure and excellent catalytic properties. These organocatalysts have been successfully applied into lots of asymmetric reactions, such as Michael addition reaction, Friedel-Crafts reaction, Morita-Baylis-Hillman reaction, Aldol reaction and so on, and made a great progress. Preparation and application of the chiral squaramide catalysts now is a hot topic in field of asymmetric catalysis research. Two kinds of novel chiral squaramide catalysts were designed and developed by our group based on our early researches, which including a series of multiple hydrogen bonding donor BINOL-quinine-squaramide catalysts and Fe3O4@SiO2megnetic nanoparticles supported chiral squaramide catalysts. Their application in different asymmetric reactions has been investigated, and excellent yields and enantioselectivities as well diastereoselectivities have been obtained. The contents of the thesis were as following:Prat1:The progress of research and application of chiral squaramid catalysts and Fe3O4@SiO2megnetic nanoparticles supported chiral organocatalysts in asymmetric catalysis was introduced according to the asymmetric catalytic reaction types.Prat2:Two kinds of chiral squaramide catalysts were successfully preparaed. One is chiral bifunctional squaramide catalysts derived from BINOL and quinine with multiple hydrogen bonding donors, high yield and excellent enantioselectivity and diastereoselectivity of these catalysts will be realized through the concerted catalysis of all the active groups. Another is the Fe3O4@SiO2megnetic nanoparticles supported chiral squaramide catalysts, these immobilized catalysts proved to be highly effective in asymmetric Michael addition and could be recycled easily without loss of the activity and enantioselectity.Part3:A set of BINOL-quinine-squaramides bearing multiple hydrogen bonding donors catalysts were used to promote the catalytic enantioselective Michael addition reaction of of β-nitroalkenes to pentane-2,4-dione, in which Cat-la was found to be the best catalyst. After screening the reaction condition, the substrate scope was next investigated. The reaction was catalyzed by Cat-la and the products were obtained with excellent ees and drs (up to>99%ee, up to>99:1dr) at low catalyst loading (0.5mol%). Further more, the methodology was applied successfully to the synthesis of enantiomerically pure isoxazole derivatives and β-amino acid esters.Part4:A chiral BINOL-quinine-squaramide bearing multiple hydrogen bonding donors Cat-la has been identified as the best catalyst for the asymmetric Michael addition of2-hydroxy-1,4-naphthoquinone to β-nitroalkenes, the Cat-la give the products with excellent yields and ees (up to99%yield and93%ee) at low catalyst loading (0.5mol%). Moreover, the catalyst also could be recycled, after3cycles, it’s also with high activity and enantioselectivty. To further illustrate the synthetic potential of this methodology, the synthesis of (S)-3-phenyl-2,3-dihydro-1H-benzoindole-4,9-dione was performed with high ee value (up to91%ee).Part5:The Fe3O4@SiO2megnetic nanoparticles supported chiral squaramide catalyst Cat-5b was successfully applied to asymmetric Michael addition of pentane-2,4-dione to β-nitroalkenes to give the products in moderate yields and good ee values (up to69%yield, up to93%ee). Furthermore, the catalyst can be easily and quickly recycled in the presence of external magnetic field and can be reused for4times without loss of the activity and enantioselectivity.