Studies On The Synthesis Of Quinolone Derivatives By Phase-transfer Catalysis

Nitrogen-containing heterocycles are a common molecular skeleton in natural products and drugs,with more than half of the marketed drug molecules containing this type of heterocycle.As a special member of the nitrogen-containing heterocycle family,quinolone derivatives have shown many important pharmacological activities,such as antihistamine,antibacterial,anti-inflammatory,antimalarial,and anticancer effects.Due to its fascinating characteristics,the synthesis of quinolone derivatives has attracted great attention in the field of organic chemistry.In recent years,many synthetic methods for quinolone derivatives have been reported,but exploring simpler and more reliable synthetic methods to efficiently construct structurally more complex and functionally diverse quinolone derivatives is still of great significance.In this thesis,a combination of readily available and inexpensive quaternary ammonium salts and potassium hydroxide was used as a phase-transfer catalytic system to promote the Michael/ammonolysis cascade reaction of cyclohexane-1,3-dione-derived enaminones and olefinic azlactones.By screening reaction conditions such as quaternary ammonium salts,inorganic bases,solvents,and stoichiometry,the optimal reaction conditions were established.Under these reaction conditions,a series of structurally diverse hydroquinoline-2,5-diones were rapidly synthesized with moderate to good yields(53-94%)and excellent diastereoselectivity(>99:1 dr in most cases).The relative configuration of the products was confirmed by X-ray single crystal diffraction and ~1H NOSEY NMR.The realization of gram-scale reaction demonstrated the potential synthetic value of the methodology.Slightly excess enantiomers were obtained in the asymmetric catalysis exploration.The product was derivatized by Suzuki-Miyaura cross-coupling,Heck coupling,reduction,and nucleophilic substitution,successfully affording structurally more complex and diverse hydrogenated quinolone derivatives.Mechanistic studies had shown that anion transfer and trace amount of water in the system were crucial for the progress of the reaction.