Copper-catalyzed Multicomponent Cascade Reactions Of Diaryliodonium Triflates,cyanamines,and Alkynylamines For The Synthesis Of Guanidines

Guanidine is a special kind of three nitrogen organic compounds,which is widely used in pharmaceutical industry and coordination chemistry because of its physiological activity diversity.At early stage,the main methods for the synthesis of guanidine are nucleophilic substitution or nucleophilic addition reaction using cyanamide,thiourea and imidazole chloride,and based on traditional condensation of guanidyl carbonyls and their analogues,these methods have some shortcomings,such as harsh reaction conditions,long reaction time and low efficiency.The synthesis strategy based on transition metal-catalyzed functionalized guanidine cyclization is a kind of efficient method developed in the past two decades.However,there are some defects,such as expensive catalyst,and tedious precursors preparation.Therefore,it is of great significance to synthesize guanidine compounds with high efficiency from simple starting materials under mild conditions.This thesis described a method of synthesizing guanidine compounds by copper-catalyzed multicomponent cascade reactions of cyanamines,diaryliodonium triflates,and alkynylamines.The research results are as follows:（1）Using K₂CO₃ as base,copper-catalyzed the rapid three-component reaction of cyanamides,diaryliodonium triflates,and propargylamine under mild reaction conditions.The reaction underwent guanidination and intramolecular 5-exo-dig hydroamination,three C-N bonds were constructed in one step to genatate 1,5-disubstituted 2-aminoimidazoles with good yield.The reaction has high chemical selectivity and regioselectivity,and has good compatibility with functional groups.（2）Using pyridine as base,copper-catalyzed the four-component reaction of cyanamides,diaryliodonium triflates,propargylamine and diaryliodonium triflates.The reaction underwent guanidination,intramolecular 5-exo-dig hydroamination,and C-N coupling in a short time,and four C-N bonds constructed in one step to efficiently genarate 1,5-disubstituted 2-aminoimidazoles.The reaction showed good universality and compatibility to substrates and active functional groups.（3）When the reaction is extended but-3-yn-1-amine,the four-component reaction of cyanamides,diaryliodonium triflates,but-3-yn-1-amine and water synthesize chain carbonyl guanidine compounds.The reaction conditions were screened and the optimal reaction conditions were obtained:DMF as solvent.K₂CO₃ as base and Cu I as catalyst at 80℃for 3 h,the yield is 53%.The reaction mainly experienced guanidination and alkyne water addition reaction,in which two C-N bonds and one C-O bond were constructed in one step.The universality of the reaction to the substrate needs to be further investigated.This thesis described a one-pot synthesis method of copper-catalyzed multicomponent cascade reactions of diaryliodonium triflates,cyanamides and alkynylamines can construct 3-4 C-N bonds quickly and efficiently.Copper has been effectively used in each step of the reaction,and good selectivity has been obtained through selection of base.In addition,we found that copper-catalyzed the four-component reaction of cyanamides,diaryliodonium triflates,but-3-yn-1-amine and water synthesize chain carbonyl guanidine compounds.This would provide an efficient and step-economic approach to rapid synthesis of guanidine compounds.