Study On Copper-Catalyzed Defluorinative Hydroarylation Of Olefins With Polyfluoroarenes

Fluorinated compounds are a class of crucial organic compounds,which widely used in pharmaceuticals,agrochemicals,materials and tracers for positron emission tomography.According to statistics,approximately 30%of all agrochemicals and 20%of all pharmaceuticals on the market contain fluorine,such as Lipitor,Lexapro and Prozac.Meanwhile,fluorine is used to tag biochemical probes for the study of various biological processes.For instance,the NMR activity of the¹⁹F nuclei enables in vivo magnetic resonance imaging.¹⁸F-positron-emitting tomography is used daily for diagnosing,staging,and detecting the recurrence or progression of various diseases including cancer.Therefore,the synthesis of containing fluorine compounds has become an important research topic in synthetic chemistry.Compared with other C–X?X=Cl,Br?bond,the C–F bond is shortest and has highest bond energy,and therefore the C–F bond is very stable in thermodynamics.Consequently,the C–F bond activation in polyfluoroarenes is very challenging.Yet for all that,there are several ways to achieve this process.The general menthods employ the performed and highly reactive metal reagents?magnesium reagents,zinc reagents,boron reagents,silicon reagents,tin reagents,lithium reagents?reacting with fluoroarenes to forge a series of C–C bond coupling products.On the other hand,the transition-metal-catalyzed defluorohydrogenation and defluoroboronization of fluoroarenes have also been reported.However,there are some shortcomings in these methods.First,the highly reactive metal reagents as the substrates are usually unstable,and have poor functional groups compatibility,and usually require relatively high temperature.Second,the methods for forging C_sp2–C_sp3 bond are far underdeveloped than that of C_sp2–C_sp2 and C_sp2–C_sp bond.Third,the substrates are limited to mono-fluoroaromatics and polyfluoroaromatics with directing groups?such as imine,oxazoline,pyridine,nitro,ketone and hydroxyl?to control regioselectivity of the C–F bond.Therefore,it is still a great challenge for realizing C–F bond activation of simple polyfluoroarenes to construct C_sp2–C_sp3bond under mild conditions.In this thesis,the defluorinative hydroarylation with cheap and readily available olefins and polyfluoroarenes as the substrates to sythesize polyfluoroarenes compounds has been achieved.Using in-situ generated CuH catalyst,which derived from dppbz ligated copper bis?2-ethylhexanoate?in the presence of silane,the hydroarylation of olefins products were obtained with high yields and regioselectivities.These reactions can be performed under very mild conditions,and furnished a variety of highly functional products through in-situ generated catalytic amount of organocopper intermediate instead of traditional stoichiometric organometallics with olfins as the feedstocks.This method not only provides a new avenue to access fluorinated arenes,but also guides a novel idea to active the inert C–F bond.