Studies On Selective C-H And C-F Bonds Functionalization Of Polyfluorobenzenes And Synthesis Of Anti-HIV Pharmacoenhancer-Cobicistat

This thesis aims at the research on the synthesis of fluorinated nitriles,diaryl ketones,diarylmethanes and fluorinated aryl ethers via selective C-H and C-F bond functionalization of polyfluorobenzenes.Also,the studies on synthesis of anti-HIV pharmacoenhancer--Cobicistat and its key symmetric chiral diamines intermediate had been developed.It was mainly divided into three aspects:1.Synthesis of fluorinated nitriles and diaryl ketones through selective C-F bond functionalization of polyfluorobenzenes under different mild conditions.A highly efficient and simple procedure was developed to synthesize substituted fluorinated nitriles and diaryl ketones under mild conditions from polyfluorobenzenes and phenylacetonitriles by changing the inert environment into oxidative conditions.It was found that both of these reactions could be obtained moderate to excellent yields after the optimization and extension of substrates.To explore the mechanism of oxidative decyanation reaction,HPLC analysis was used to monitor the process.In addition,some control experiments were carried out to determine the source of the oxygen atom in the ketone derivatives.Furthermore,a possible mechanism based on the sequential S_NAr substitution of polyfluorobenzenes and the in situ oxidation of secondary nitrile was proposed.2.Synthesis of diarylmethanes and fluorinated aryl ethers via selective C-H and C-F bond of polyfluorobenzenes under metal-catalyzed and metal-free conditions.A novel and efficient palladium-catalyzed cross-coupling benzylation reaction of pentafluorobenzene via selective C-H functionalization and synthesis of fluorinated aryl ethers via selective C-F functionalization under metal-free conditions have been developed.We have optimized these reaction conditions and investigated the scope of substrates.Also,a possible mechanism of benzylation was proposed.In this part,we have developed a new strategy of cross-coupling between Csp~2 and Csp~3,which could achieve selective C-H and C-F functionalization of polyfluorobenzenes by controlling the reaction conditions.3.Synthesis of anti-HIV pharmacoenhancer--Cobicistat and its key symmetric chiral diamines intermediate.In order to avoid the disadvantages in the synthesis of Cobicistat especially in its key intermediate,we had explored several strategies to construct symmetric Csp~3-Csp~3,such as Mcmurry reaction and Wittig-Horner reaction,and various protecting groups of amino.A novel synthetic route of key intermediate based on Wurtz coupling had been developed.This new method shortened the procedures,simplified the operation,avoided using toxic reagents and most important improved the yield of intermediate up to 60%.On the basic of the intermediate,total synthesis and optimization of Cobicistat had been completed,which would made contribution for the industrial production.