Studies On The Synthesis Of Quinolones, Isocoumarins And Phthalides

Over the years,4-quinolones, isocoumarins and phthalides have attracted considerableattention from medicinal chemists due to their diverse biological and pharmacologicalactivities.4-Quinolones have been investigated as antibacterial, antiviral, antimitotic,antidiabetic, antitrypanosomal, antitumor agents and HIV-1integrase inhibitors.Isocoumarins and phthalides represent an important class of naturally occurringlactones exhibiting anti-microbial, anti-tumor, anti-HIV and anti-inflammatory activities.Besides, isocoumarins and phthalides are useful synthetic intermediates, particularly forfurther elaboration to other biologically heterocyclic and carbocyclic compounds.The first part (Chapter2) describes an efficient palladium-catalyzed tandem aminationprotocol for the synthesis of1,2-disubstituted4-quinolones from easily accessiblechalcones and primary amines, in which the catalyst plays a dual role including Buchwaldcoupling and catalytic dehydrogenation. The second part (Chapter3and Chapter4)provides a simple and efficient method for the synthesis of isocoumarins and phthalides viatert-butyl isocyanide insertion using Pd(OAc)2/DPEPhos and NiCl2/DPPE as the catalystsystem respectively.Characterized by mild reaction conditions and good to excellent yields, theseapproaches provide one of the simplest methods for the synthesis of this class of valuablecompounds, and a wide range of multisubstituted molecules could be generatedaccordingly for chemical library construction.