Metal-Free [2+2+2] Cycloaddition Reaction Of Ynamides With Nitriles

Ynamide is an alkyne with a special structure,in which the alkynyl is directly attached to the nitrogen atom.The conjugation of the nitrogen lone pairs to the triple bond,as well as the alteration of activity caused by the electron-withdrawing-group on the nitrogen,let ynamide performes well at the aspect of regioselectivity and stereoselectivity in reactions.With the development of ynamide chemistry,ynamide is increasingly involved in cycloaddition reactions such as [2 + 2],[4 + 2],[2 + 2+ 2],and showed excellent reactivity and application potential.Up to now,the cycloaddition reaction of the ynamide has become one of the effective methods for the construction of heterocyclic compounds.Pyridine compound is one of the most studied systems in heterocyclic compounds and can be used in many aspects such as pesticides,pharmaceuticals,antibacterial fungi,feed additives,dyes,surfactants,catalysts,etc.Pyrimidine compound is a class of important substances in life activities,not only in the human body,but also in many natural drugs.2,4-diaminopyridine and 4-aminopyrimidine as the very important branch of pyridine and pyrimidine compounds,respectively,also have important medical research significance and practical value.Therefore,exploring more moderate and highly efficient synthetic methods is crucial for expanding the diversity of these two catagories and is also of great significance for practical application.In this dissertation,we introduce a novel and efficient [2+2+2] anulation reaction between ynamides and nitriles catalyzed by lewis acid,to synthesis 2,4-diaminopyridines and 4-aminopyrimidines.This method has the advantages of simple operation,mild reaction condition,high yields,and wide substrate scope.More importantly,the method firstly realizes metal-free [2+2+2] cycloaddition reaction of ynamides with nitriles,whose regioselectivity depends only on the steric hindrance of the ynamide's alkynyl terminal substituents.When the alkynyl terminal substituent of the ynamide is an alkyl group,the product is a 2,4-diaminopyridine,while when the substituent is an aryl group,the product is a 4-aminopyrimidine.In summary,this method provides a convenient and efficient method for the synthesis of 2,4-diaminopyridines and 4-aminopyrimidines.