Study On Synthesis Of Difluoroalkylated Quinazolinones

When fluorine atoms or fluorine-containing groups are introduced into organic compounds,their physical,chemical,and physiological properties?such as lipophilic,metabolic stability,ability to bind to target proteins,cell membrane penetration,and bioavailability?are usually significantly improved compared with their parent molecules.Therefore,fluorination has gained wide attentions in pharmaceutical chemistry,organic chemistry and material chemistry by researchers.Compared with the introduction of F and CF₃,the introduction method of CF₂ is relatively rare.As an important fluorogroup,ethyl difluorobromoacetate can not only introduce CF₂ into the molecule easily,but also introduce other functional groups at the same time.Therefore,it has greater advantages over direct fl uorination in terms of economy and practicability of the synthesis.At the same time,the rapid development of radical chemistry provides a novel way for difluoroalkylation.As a kind of special substituted olefin compounds,N-cyanogen alkenes have many functional groups and reaction sites at the same time.Quinolinone is an important alkaloid and active molecule which exists widely in nature.In this paper,N-cyanoamine olefins were used as the central substrate to study different cyclic reactions catalyzed by Cu/B₂Pin₂ system or catalyzed by fac-Ir?ppy?₃.Difluoroalkylated quinolones were synthesized by using Cu as catalyst and B₂Pin₂ as reducing agent under the condition of heating.The method utilized the reducing property of B₂Pin₂,reduced the amount of catalyst,and obtained high yield under mild reaction conditions.Employing fac-Ir?ppy?₃ as photocatalyst,a series of quinolinone pentacyclic and hexacyclic ring systems were synthesized by using N-cyanamide alkene and ethyl difluorobromoacetate as template substrates under the condition of visible light irradiation.Compared with the traditional method using peroxide and other conditions,this approach provides a mild and efficient way.