Study On The C-N And C-S Coupling Reactions With Trisarylbismuths

The construction of carbon-nitrogen bonds and carbon-sulfur bonds catalyzed by transition metals is widely used in pharmaceutical chemistry,functional materials and total synthesis of natural products.For the construction of these two types of chemical bonds,the commonly used arylation reagents reported in the literature mainly include aromatic halogenated hydrocarbons,aryl trifluoromesylate,high-valent iodine reagents,as well as aryl boric acid,aryl zinc,aryl magnesium and other transmetallic reagents.However,this kind of reagent has some shortcomings such as halogen ion contamination,complex preparation process or unstable structure,which is not easy to preserve.Therefore,it is very necessary to develop other types of arylation reagents with stable structure,simple preparation,safety and green preparation.Triarylbismuth is an excellent organometallic reagent,which can be used as catalyst,ligand or arylation reagent in organic synthesis because of its weak carbon-bismuth bond energy.In addition,these compounds have the advantages of easy preparation and preservation,low toxicity or non-toxicity of bismuth-containing materials and byproducts,high reactivity and mild reaction conditions.Based on this,this paper mainly uses triarylbismuth as an arylation reagent for the synthesis of triarylamine and 2-（arylthioyl）pyridine-1-oxide and its derivatives,providing a new synthesis method for the construction of carbon-nitrogen bonds and carbon-sulfur bonds.Part I,two synthetic routes were designed according to the method of references.Sixteen triaryl bismuth and three triaryl antimony were prepared at the scale of gram,and their structures were characterized.Method 1:10 kinds of triaryl bismuth and 3 kinds of triaryl antimony were synthesized from bismuth trichloride and aryl Grignard reagent in a yield of 28-88%;Method 2:6 kinds of triaryl bismuth compounds were synthesized from magnesium metal,bismuth trichloride and bromide in a"one-pot"method,with a yield of 22-62%.Part II:The synthesis method of triarylamine was established by C-N coupling reaction involving triarylbismuth as arylation reagent.Firstly,the coupling reaction of diphenylamine and triphenylbismuth was taken as the model reaction,and the influencing factors such as catalyst,base,solvent,reaction temperature and reaction gas atmosphere were optimized to obtain the optimal reaction conditions:Cu（OAc）₂ as catalyst,1,2-dichloroethane（DCE）as solvent,Et₃N as base,reaction under oxygen atmosphere at 90℃for 12 h,the model reaction with 99%high yield to obtain the corresponding coupling products.Secondly,under optimal conditions,the applicability of different substituted triarylbismuth and high resistance secondary amine substrates was studied.A total of 32 substrates were expanded,with yields ranging from 62-99%.4 symmetric and 4 asymmetric triarylamine compounds were synthesized from aniline by"one-pot one-step method"and"one-pot two-step method"with other reaction conditions unchanged.The yields were 60-96%and 55-97%,respectively,by adjusting the amount of triarylamine.In addition,we also studied the application of primary heterocyclic amines and primary aliphatic amines as substrates.Under the optimal reaction conditions,by controlling the dosage of triarylbismuth,5 single arylated products and 3 double arylated products were successfully obtained,with yields of 49-85%and49-94%,respectively.Finally,the mechanism of the reaction is speculated.The reaction mainly goes through the processes of transmetallization,reduction elimination,oxygen oxidation catalyst regeneration,etc.In this system,the triaryl bismuth is also prone to the aryl self-coupling reaction to form biphenyl and other byproducts.Part III:The synthesis method of 2-（arylthiopyridine）-1-oxide and its derivatives was established by C-S coupling reaction involving triarylbismuth as arylating reagent.Firstly,the C-S coupling of Cu PT and triphenyl bismuth was used as the model reaction.The conditions of reaction solvent,type and amount of base,temperature and atmosphere of reaction gas were optimized,and the optimal conditions were determined.DMF as solvent,pyridine as base,and the model reaction rate reached 96%under the condition of no additional copper source after 12 h reaction at 50℃.Secondly,under the optimal conditions,the applicability of different substituted triarylbismuth to Cu PT coupling reaction was studied.20 substrates were expanded,and the yield was between 68-99%.For triarylantimony,the coupling reaction can also occur smoothly,and the corresponding coupling products are obtained at 93%,95%and 99%high yields in the three examples,respectively.Since Cu PT is prepared by pyridinthione sodium（Na PT）and Cu SO₄·5H₂O under alkaline conditions,we studied the C-S coupling reaction between pyridinthione sodium（Na PT）and triarylbismuth under added copper source.The results showed that under the same reaction conditions,only Cu SO₄·5H₂O was added as the catalyst to achieve the coupling of pyridyl thione sodium（Na PT）and triarylbismuth,and expanded 16 substrates,the yield between 53-99%.Finally,with Cu（OAc）₂ as the catalyst,the selective C-S coupling of amino/hydroxybenzene-mercaptan and triarylbismuth was successfully achieved,and 13 substrates were expanded,with yields ranging from 66-99%.The reaction mechanism is similar to the C-N coupling reaction,but the amount of byproduct biphenyl is less than the C-N coupling reaction.To sum up,this thesis mainly carried out the research of C-N and C-S coupling reaction with triarylbismuth as the cross-coupling arylation reagent,and realized the N-arylation reaction of high-hindered secondary amine and the S-arylation reaction of Cu PT（or Na PT or substituted phenylthiophenol）with high efficiency and high substrate adaptability.The method established in this thesis provides new ideas and options for the construction of C-N bonds and C-S bonds.