A Study On C-C Coupling Reaction Catalyzed By N,O-Bidentate-Coordinated Palladium Complexes

The transition metal-catalyzed C-C coupling reaction is one of the most important methods for constructing new carbon-carbon bonds.It is widely used in the synthesis of functional organic molecules and drug molecules.The development of new catalysts or catalytic systems has always been an important research hotspot in this field,and it is also a challenging research direction.On the other hand,palladium complexes derived from nitrogen-containing heterocycles have been proven to be an important catayst for C-C coupling reaction.Novel ligand-derived palladium complexes are still the goal pursued by synthetic chemists.This thesis is mainly based on N,O-bidentate coordinated palladium complexes synthesized in our laboratory in the early stage,and their catalytic properties in three type of C-C coupling reactions are studied.This thesis contains the following four sections:Part 1 IntroductionThe recent research progress of the Heck,Suzuki,Sonogashira coupling reactions catalyzed by transition metal palladium complexes is summarized.Part 2 The Heck reaction of halogenated aromatics and olefins catalyzed by N,O-coordinated palladium complexesUsing p-bromoacetophenone(1a)and methyl acrylate(2a)as template substrates,the effects of palladium complex(I-IV),base,solvent,temperature and other factors on the model reaction were investigated.The best conditions are:II(5 mol%),Et₃N(2 equiv),DMF,130?,1a/2a=1:1.5,1.5 h.The substrate scope of Heck reaction was explored.The reaction has good functional group compatibility,and various substrates with electron-withdrawing or electron-donating groups can undergo coupling reactions smoothly,and corresponding products can be obtained in good yields.Aryl bromide with strong electron-withdrawing group(4-acetyl,4-formyl,4-methoxycarbonyl,4-cyano,3-nitro,2-nitro)shows higher activity than those with electron-donating groups(4-methyl,4-tert-butyl,4-methoxy,4-benzyloxy),while electron-deficient olefin derivatives can all participate well in the reaction.The results show that the electronic effects and spatial positions of the substituents have a certain effect on the reactivity of the substrates.In addition,2,6-dibromopyridine and 1-bromonaphthalene can also reacted with methyl acrylate to obtain the target product in higher yields.Part 3 The Suzuki reaction of halogenated aromatics and arylboronic acids catalyzed by N,O-coordinated palladium complexesTaking the reaction of p-bromoacetophenone(1a)and phenylboronic acid(2a)as a template,and by examining the effects of palladium complex,base,solvent,temperature and other factors on the template reaction,the optimal conditions were determined as:III(5mol%),K₂CO₃(2 equiv),DMF(1 m L),110?,1a/2a=1:1.5,2h.Under the optimal conditions,the substrate range of the reaction was further expanded,and the reaction showed good functional group compatibility.Firstly,the coupling reaction of p-bromoacetophenone with phenylboronic acid containing different substituents was studied.Phenylboronic acid with a strong electron-withdrawing group at the para-position was more active than those with the electron-donating group with a yield of up to 97%.This shows that the electronic effect of groups has a significant influence on the reaction.When a substituent is present in the meta or ortho position,the reactivity of the phenylboronic acid with an electron-donating group is significantly improved,which indicates that there is a steric hindrance effect on the activity of the substrate by the position of the substituent.Next,we extended the substrate range of aryl bromide,and a series of aryl bromides containing different groups were used in this coupling reaction.Similarly,the electronic effect and steric hindrance of the substituents on bromobenzene have an influence on the activity of the substrate,and bromobenzene with an electron-donating group shows a lower reactivity.Finally,the Suzuki coupling reaction between some highly active substrate molecules was further extended,and the corresponding products were obtained in good yields.This reaction provides an efficient and convenient synthetic method for the preparation of biaryl derivatives.Part 4 The Sonogashira reaction of aryl halides and alkynes catalyzed by N,O-coordinated palladium complexesUsing 4-iodobenzonitrile(1a)and phenylacetylene(2a)as templates,the reaction parameter such as palladium complex,bases,solvents and temperatures were screened to obtain the optimal conditions:1a/2a=1:2,II(5%),CuI(0.5 equiv),K₂CO₃(2 equiv),DMF,120?,1h.Then substrates scope of Sonogashira reaction was explored.It was found that the reaction of an electron-withdrawing aryl iodobenzene with phenylacetylene can obtain the products in higher yield.The iodohydrocarbon having a substituent as an electron donating group also has good reactivity.