Investigation On Palladium-Catalyzed Selective Transformations Of Haloalkynes

Haloalkynes,as a class of easily available organic compounds with multiple reaction sites and abundant reactivities,have been widely used in synthetic chemistry.In terms of chemical structure,haloalkynes have carbon-carbon triple bond and carbon-halogen bond,both of which are easy to interact with transition metals.Therefore,over the past decades,transition metal-catalyzed transformations involving haloalkynes have gradually become a highly potential research field in organic synthesis.Among them,the palladium-catalyzed reactions of haloalkynes owning diversity and high efficiency,have played an important role in the synthesis of complex functionalized molecules.However,how to control the sequential and selective conversion of haloalkynes is still a hot and challenging issue that has attracted much attention.In this thesis,the research progress of transition metal-catalyzed transformations of haloalkynes is reviewed.In this context,based on our continuous interest in haloalkyne chemistry and palladium chemistry,we have systematically and deeply explored a series of palladium-catalyzed selective transformations involving haloalkynes.Through the selective breaking and recombination of carbon-carbon triple and carbon-halogen bonds in haloalkynes and chemical bonds in other substrates,we realized the construction of various compounds including 2-alkynylindoles,7-alkynylindoles,3-bromoindoles,3-halopyrroles and 1,3-dienes.See the following for specific researchs:(i)Palladium-catalyzed and primary amine-directed C2-selective C-H alkynylation of indoles has been developed.A series of functionalized 2-alkynylindoles have been obtained by employing haloalkynes as efficient alkynylating reagent,primary amine as directing group and water as single solvent.This reaction features easy available starting materials,simple and mild conditions as well as broad substrate scope.Moreover,the gram scale synthesis and the derivatizations of the alkynylated products have been achieved,further demonstrating the potential applications in synthetic chemistry.Mechanistic investigations suggest that the cleavage of C2-H bond of indoles should be the rate-determining step in this reaction.(ii)Palladium-catalyzed and di-tert-butylphosphinoyl-directed C7-selective C-H alkynylation of indoles has been established.In this protocol,the C-H bond at the C7 position of indoles can be activated under the catalysis of palladium by using di-tert-butylphosphinoyl as an efficient directing group.Meanwhile,the alkynyl fragment can be successfully introduced into indole ring with the help of the oxidative addition process between palladacycle intermediate and carbon-halogen bond of haloalkynes,affording various substituted 7-alkynylindoles in moderate to good yields.In addition,the directing group used in this reaction can be easily removed,which is conducive to the diversity transformations and applications of the product.(iii)Palladium-catalyzed oxidative C-H activation/annulation of N-alkylanilines with bromoalkynes has been achieved for the construction of functionalized 3-bromoindoles.This reaction undergoes the insertion of bromoalkyne into the N-Pd bond,C-H activation,reductive elimination of palladacycle intermediate,leading to the selective conversion of carbon-carbon triple bond in bromoalkyne,in which high atom economy,excellent chemoand regioselectivities,as well as good functional group tolerance have been shown.The retention of bromine atom in this reaction allows the product to be further converted to various functionalized indole derivatives through cross-couplings under simple reaction conditions.(iv)Palladium-catalyzed tandem annulation strategy for the assembly of 3-halopyrroles from N-alkylanilines and haloalkynes has been realized.In this reaction,3-bromopyrrole and3-chloropyrrole derivatives have been constructed with high chemo-and regioselectivities using two molecular haloalkynes and one molecular N-alkylanilines as substrates,and the carbon-carbon triple bond and carbon-halogen bond in haloalkynes can be efficiently transformed in one single step.In addition,the reaction has the characteristics of easily available starting material properties,simple operation and good functional group tolerance.Meanwhile,the products can be easily transformed to different functionalized pyrrole compounds.(v)Palladium-catalyzed sequential three-component cross-coupling of alkenes,bromoalkynes and boronic acids to 1,3-dienes has been accomplished.In this method,alkenes are employed as hydride and alkenyl donors.This reaction proceeds smoothly under mild conditions with excellent stereoselectivity and good functional group tolerance.Mechanistic studies indicate that reaction processes might include the cross-coupling of bromoalkynes and boronic acids involving the formation of internal alkyne intermediate and the hydroalkenylation of internal alkyne and alkenes catalyzed by palladium hydride species.The required initial palladium hydride species might be fromed by the Heck reaction between alkenes and boronic acids.