Transition Metal Copper-Catalyzed Synthesis Of Propargylamines And Its In Situ Conversion

In the fields of medicinal chemistry and organic synthesis,extremely extensive reports on propargylamine and its derivatives have been described due to these compounds are not only considered as building block for the preparation of a series of nitrogen-containing bioactive compounds and natural products,but also show good biological activity in the treatment of neurodegenerative diseases.In view of this,the development of a simple and efficient method for the synthesis of propargylamine has attracted great attention from the chemists.Among them,the discovery and development of the three-component coupling reaction of aldehyde,amine,and acetylene?commonly referred to as A³ coupling?provided a convenient way for the synthesis of propargylamines,However,there are still many limitations in the construction of secondary propargylamine.Therefore,development of a new method for the synthesis of propargylamines is still desired.Based on theses,this thesis proposes 1)Transition metal copper catalyzed oxidative deamination/alkynylation in an A³-type coupling reaction;2)A series of 2-oxazolidones were constructed by copper-catalyzed decarboxylative A³coupling/CO₂cyclization using the in situ formed propargylamine and.The second chapter of this thesis specifically introduced a new method for the synthesis of propargylamines instead of the classical A³ coupling reaction using copper as a catalyst:This protocol proceeded with a CuBr₂/TBHP system through a process of oxidative deamination of primary amines to imine,and then this imine intermediate was further captured by the alkyne,and finally 25 new propargylamine compounds were produced in good yield.The whole process has the advantage of a short reaction time,a wide range of substrates,good functional group tolerance and simple operation.In addition,when two different amines were used,the reaction could also work smoothly and show high chemoselectivity under the standard conditions.Next,a series of oxazolidinone derivatives were synthesized in the presence of copper catalyst.The reaction involved a process of the annulation of the in situ generated propargylamine and releasing CO₂ from decarboxylative A³ coupling of?-carbonyl acids,amines,and alkynes.Meanwhile,the scope of?-carbonyl acids,amines and alkynes was evaluated,providing a diversity of oxazolidone derivatives.This strategy effectively avoided the preparation and separation of propargylamines,and also overcame the limitation of traditional processes depended on a high-pressure CO₂ or precious metals,which reflects a good environment and process friendliness?corresponding to chapter III of this article?.