Study On Transition Metal-Catalyzed Coupling Reactions Using Haloalkynes As Substrates

In recent years,haloalkynes have been widely used in medicine chemistry,chemical industry,food,materials and other fields due to their easy availability,high reactivity,and multiple reaction sites.Halogen atom could activate the triple bond,so the haloalkynes has higher reactivity than the alkynes.Haloalkynes not only have the activity of the terminal alkyne,but also easily undergo oxidative addition with transition metals.Therefore,the haloalkynes can achieve some reactions but the terminal alkynes cannot be realized.Currently,many research results have been obtained based on the nucleophilic addition,alkynylation,tandem reaction and annulation of haloalkynes.However,there are also many challenges in the haloalkyne chemistry that need to be solved.Therefore,how to achieve the chemical-and regio-selective reactions of haloalkynes with high efficiency and high step economy is still a hot spot and difficulty for organic chemists.In continuation of our strong interest in the field of haloalkyne chemistry,we thoroughly studied on transition metal-catalyzed nucleophilic addition and tandem annulation reactions using haloalkynes as substrates.In addition,the controllable alkynylation of 2-aminobiphenyl derivative has been achieved,a series of methods for building new carbon-carbon and carbon-heteroatom bonds with high efficiency,high step economy and high regioselectivity have been developed to synthesize various of(Z)-vinyl thiocyanates,3-substituted isocoumarins,alkynylating biaryl-2-amines and6-methylene-6H-dibenzo[b,d]pyrans derivatives.The details are summarized as following:In chapter two,we developed the silver-catalyzed nucleophilic addition of potassium thiocyanate to haloalkynes obtained the corresponding vinyl thiocyanates in exclusive regioselectivity.The usage of inexpensive and nontoxic nucleophile and solvent makes this method more attractive and environmental friendly.This strategy exhibits broad substrate scope and gram-scale synthesis.In addition,the halogen atom of haloalkynes is retained,making further transformation on the scaffold possible,which allows the synthesis of heterocycle and trifluoromethyl sulfides compounds via convenient operation.In chapter three,we report a novel protocol for the synthesis of 3-substituted isocoumarins via Pd-catalyzed nucleophilic annulation of bromoalkynes with benzoic acids.DPEPhos was used as ligand.This transformation was highly dependent on the Pd(0)generated in situ and construction of C(sp~2)-O bond and C(sp~2)-C(sp~2)bond in one step.Mechanistic studies revealed that the protocol might proceed via nucleophilic addition and C-H activation procedure.In addition,the C-H bond cleavage process should be the rate determining step in the catalytic process.It is noteworthy to mention that the reaction was rather sensitive to solvent.In chapter four,the first example of the palladium-catalyzed primary amine-directed controllable alkynylation of biaryl-2-amines has been developed by using haloalkynes as an alkynylating reagent.The alkynylation products could be selectively obtained by adjusting the stoichiometries of substrates,this reaction using primary amine as a directing group which has an atom economy and step economy than other nitrogen-containing DGs.This transformation features broad substrate scope and good functional group tolerance.We proposed that the protocol may proceed through a Pd(II)/Pd(IV)catalytic process.In chapter five,we report an novel transformation for the synthesis of6-methylene-6H-dibenzo[b,d]pyransviapalladium-catalyzedsequentialC(sp~2)-H alkynylation/annulation of 2-phenylphenols with haloalkynes.This protocol features a traceless directing group strategy,unique regioselectivity and mild reaction conditions.The annulation process could be envisioned to follow two possible mechanisms.In the path a,the procedure would begin with activation of the palladium(II)-catalyst to alkyne moiety of the intermediate,which would trigger cis-addition of the intermediate to generate product.In an alternative scenario,undergoing a sequential trans-oxypalladation and protodepalladation,the desired products could also be obtained.