Synthesis Of Heterocycles Via Annulations Of Propargyl Amines/Alcohols

Heterocycles are the key moieties in many pharmaceutical intermediates and potentially biologically active molecules,and also occur in natural products.It is one of the important research topics to design and develop the multi-component annulation to construct heterocyclic structure in catalytic synthetic chemistry,pharmaceutical chemistry and organic material chemistry.Cycloaddition reaction of alkynes is one of the important organic transformation for developing the synthetic reactions with high atom utilization,and propargyl amines and propargyl alcohols have been widely applied in the synthesis of heterocyclic compounds.The purposes of this dissertation is to develop the efficient synthetic methods for the formation of N-and O-heterocyclic compounds,and the research work focused on the annulation of propargyl amines or propargyl alcohols to provide the protocols for the formation of multi-substituted pyridines,pyrroles and naphtho[2.1-b]pyran-2-carboxamides.In chapter 1,the recent advances in the synthesis of O-and N-heterocycles by using propargyl alcohols,propargyl amines and their derivatives as one of reactants was summarized.The cited literatures show the well-applied propargyl compounds as the versatile synthons in the synthesis of various heterocycles.In chapter 2,in the presence of silver salts,the annulation of terminal propargyl amines with electron-deficient alkynes was designed and studied.It has been found that under the different reaction conditions,propargylamines and N-methyl propargylamine underwent[4+2]and[3+2]cycloaddition reactions with electron-deficient alkynes with excellent chemoselectivity,when K₂S₂O₈ and DBU were used as additives,providing the efficient synthetic methods for the synthesis of multi-substituted pyridines and pyrroles.In chapter 3,with the use of cheap Lewis acids of ZnI₂ and FeCl₃ as catalysts,a three-component cyclo-coupling reaction of?-naphthol,propargyl alcohols and cyclohexyl isocyanide has been studied under air atmosphere to develop the synthetic method of 3H-naphtho[2.1-b]pyran-2-carboxamides in good to high yields.The proposed mechanism involves Lewis acid promoting the formation of allenyl carbocation intermediate and it's electrophilic substitution reaction with naphthol?-position,the cyclization giving the key intermediate having Zn-C bond,as well as a sequent insertion of isocyanide into Zn-C bond to give the precursor for the formation of amide group.The use of NBS as electrophiles resulted in the formation of2-bromo-1-phenyl-spiro[naphtho[2.1-b]pyran-3,1'-cyclohexane],so as to confirm the reactivity of C-Zn bond.The developed two catalytic systems in this dissertation have the advantages including the use of cheap and easily available catalysts,catalytic systems being not sensitive to air and moisture,reaction with high atom utilization and high selectivity.The results obtained in this dissertation have developed the application of propargyl amines and propargyl alcohols in the synthesis of N-and O-containing heterocycles.