The Construction Of Nitrogen-containing Heterocyclic Compounds Based On Bifunctional Reactions Of Maleimides And Electron-deficient Olefins

The maleimide is the key structural unit presented in the broad range of natural products,pharmaceuticals,biologically active molecules and functional materials.Meanwhile,it can act as a useful building block for the synthesis of complex natural products.Nitrogen-containing heterocyclic compounds have begun to draw interests from researchers due to the feature of their unique biological activity,easily chemical modification and convenient introduction of various functional groups.Therefore,development of novel,efficient,and operationally simple methodologies for the synthesis of nitrogen-containing heterocyclic compounds are of great importance.This dissertation is aimed at the development of transition-metal-catalyzed or nonmetallic-catalyzed oxidative cyclization reaction between maleimides and enamines,aldehyde hydrazones or?-bromoacetophenones.The whole work contains the following chapters:Chapter ?:In this part,the recent progress of maleimides in organic synthesis methodology was reviewed.Maleimides have been widely used in the chemical reactions such as conjugate addition reaction,oxidative coupling reaction and cycloaddition reaction due to its unique molecular structures including unsaturated imide and electron-deficient carbon-carbon double bonds.On this basis,we try to synthesize a series of nitrogen-containing heterocyclic compounds via maleimides with the annulation reaction precursors such as enamines,aldehyde hydrazones and?-bromoacetophenones.Chapter ?:CuCl-catalyzed oxidative cyclization of maleimides with amines and alkyne esters has been successfully realized.In the presence of catalytic amount of CuCl,maleimides with amines and alkyne esters were allowed to react in DMSO at90?for 5 h,affording the corresponding dihydropyrrole derivatives in 40⁸8%yields.Furthermore,the combination of dihydropyrrole formation and subsequent dehydrogenation aromatization in one process was realized in our copper-catalyzed process.When the above mentioned reaction conditions were altered slightly,with the addition of K₂S₂O₈ in DMSO at 90°C for another 12 h,the pyrrole derivatives were isolated as single products in high 42-72%yields.The reaction features mild conditions,a relatively broad scope,and high efficiency.Chapter ?:DABCO-catalyzed double cascade cycloaddition of maleimides with bisarylhydrazones has been explored.With the readily available DABCO as the catalyst,maleimides and bisarylhydrazones were allowed to react in DME at 70?for 12 h and the corresponding pyrazolo[5,1-c][1,2,4]triazole derivatives were obtained in 37-91%yields.It proceeds with high step-and atome fficiency and shows a broad substrate scope and functional group tolerance,making it an efficient approach for the preparation of fully substituted pyrazolo[5,1-c][1,2,4]triazole derivatives.Chapter ?:CuCl-catalyzed oxidative coupling of maleimides with hydrazones has been developed.In the presence of catalytic amount of CuCl,maleimides and hydrazones were allowed to react in DMF at 80?for 2 h,furnishing the corresponding pyrrolo[3,4?c]pyrazole compounds in 57-95%yields.Furthermore,the combination of dihydropyrazole formation and subsequent dehydrogenation aromatization in one process was realized in our copper-catalyzed process.When the above mentioned reaction conditions were altered slightly,with the addition of BTI in DMF at 80°C for another 10 h,the pyrazole derivatives were isolated as single products in high 47-84%yields.The reaction features high yields and good functional group compatibility,offering the opportunity for the further functionalization.Chapter ?:Iodine-catalyzed regioselective oxidative cyclization of aldehyde hydrazones with electron-deficient olefins has been reported.In the presence of catalytic amount of molecular iodine,BPO as oxidants,electron-deficient olefines and aldehyde hydrazones were allowed to react in CH₃CN at 80?for 6 h,obtaining the corresponding pyrazole compounds in 56-90%yields.Besides,when?-alkyl substituted acrylates were used as substrates,TBHP as oxidant,electron-deficient olefines and aldehyde hydrazones were allowed to react in CH₃CN at 80?for 2 h,obtaining the corresponding dihydropyrazole compounds in 52-86%yields.The overall simplicity and regioselectivity of the catalytic system make this approach a valuable and step-economical tool to construct a C-C bond for the synthesis of Mefenpyr-Diethyl.Chapter ?:A reductive radical relay strategy for the construction of fused benzo[e]isoindole-1,3,5-trione through a reaction of?-bromo ketones with maleimides in the presence of Ir?ppy?₃ and K₂HPO₄ in CH₃CN under visible-light irradiation for 20 h is described.A varity of benzo[e]isoindole-1,3,5-triones were obtained in 27-89%yields.The protocol employs very mild reaction conditions and offers satisfactory yields.Moreover,when o-bromo-substituted or p-bromo-substituted substrates were carried out under the standard conditions,the single products were obtained.On the contrary,when m-bromo-substituted substrates were implemented under the standard conditions,no regioselective products were achieved.Instead,the corresponding isomers were observed respectively.