Studies On Some Domino Reactions And Multicomponent Reactions Involving Terminal Alkynes

Domino reactions and Multi-component reactions(MCRs)have been highlighted as one of research frontier,widely used for the construction of heterocycles and in enantioselective synthesis and total synthesis.In this thesis,domino reactions and MCRs involved terminal alkynes are explored for the construction of arens and heterocycles.The discussions and results are listed as following:1.The N-sulfonyl ketenimine in situ generated by the Copper-catalyzed click reaction of terminal alkynes and sulfonyl azides,undergo a domino intramolecular addition-cyclization-dehydration sequence with special synthons bearing nucleophile and electronphile simultaneously:(a)The copper-catalyzed MCRs of terminal alkynes, sulfonyl azides and salicaldehydes furnish iminocoumarins,and the method is extened to 2-aeylphenols,2-acylanilines,potassium salt of 2-thiobenzaldehyde for the construction of substituted iminocoumarins,iminodihydroquinolines, iminothiochromenes respectively.(b)The copper-catalyzed MCRs of terminal alkynes, sulfonyl azides and 2-acylaziridines furnish Z-5-arylidene-2-imino-3-pyrrolines and the stereochemistry is established by NOESY analysis.(c)The copper-catalyzed MCRs of terminal alkynes,sulfonyl azides and iminophosphoranes are also explored for the synthesis of stabilized phosphorous arnidines.All the methods are general and efficient,while deuterium-labeling experiments are carried out to view the sight of the domino reactions.2.A TEA-catalyzed domino reaction(A₃B₂)of propiolates(3 equiv.)and benzaldehydes(2 equiv.)are developed.The reaction is temperature dependant:(a) the product is 2,3,9,9a-tetrahydro-naphtha[2,3-b]furan when the reaction is carried out at -40℃for 3h and quenched by 1N HCl.(b)the product is naphthalene when the reaction is carried out at -20～-10℃for 5h and then under reflux for 5h.(c)the product isβ-hydroxyl-naph.thalene when the reaction is carried out at -20～-10℃for 5h and then kept at rt for 5h.The insight of the domino reaction is viewed by the deuterium-labeling reaction and several controlled reactions and a possible mechanism is proposed.Furthermore,2,3,9,9a-tetrahydro-naphtha[2,3-b]furan is aromatized to naphthofuran exhibiting strong fluoresence.The TEA-catalyzed MCRs of propiolates,aryl aldehydes and DMAD for access to furans are also developed and the structure is established by X-ray analysis.The procedure is general and efficient and a possible mechanism is outlined.3.A novel synthesis of Hantzsch-type N-substituted 1,4-dihydropyridines from salicaldehydes,ethyl propiolate and amines has been developed.Salicaldehydes were treated with ethyl propiolate in the presence of N-methylmorpholine to give ethyl 3-(2-formylphenoxy)-propenoates.Three equiv of ethyl 3-(2-formylphenoxy)-propenoates reacted with one equiv of amines under trifluoroacetic acid(TFA)catalyst to furnish the corresponding N-substituted 1,4-dihydropyridines in good to excellent yields,recovering the starting material salicaldehydes.A possible mechanism for the domino process was proposed. Furthermore,the products can be easily derived via further transformations and three of them exhibited strong fluorescence.4.A novel,efficient and general domino reaction of 2-acyl-aziridines with the Huisgen zwitterions to furnish 2-pyrazoline rings is described.The Huisgen zwitterion in situ generated by PPh₃ and dialkyl azodicarboxylate is intercepted by 2-acylazridine to undergo a domino reaction for achievement of pyrazoline in quantitative yield,releasing Ph₃PO.The structure is firmly established by X-ray analysis and the deuterium-labeling reactions are carried out.A possible mechanism for the domino sequence is proposed.Furthermore,the resulting pyrazolines are converted to pyrazoles in acidic methanol solution under reflux.5.A facile parallel synthesis of polysubstituted 2,6-dicyanoanilines via microwave-promoted three-component reaction of aldehydes,ketones and propanedinitrile in solution and also on polymer support(PEG4000)has been developed.The structure of the compound is confirmed by X-ray analysis.The method is general and efficient.The screening for optical properties identified two new compounds with high fluorescence quantum yields. 6.A novel and facile synthesis of indole via domino reaction of N-aryl amide and Ethyl diazoacetate has been established.The structure of the compound is confirmed by X-ray analysis and the methodology could be utilized to indole-fused heteroeyeles preparation.