Metal-Free Hydroalkoxylation Of Ynamides

Ynamides are alkynes that are connected with amide.Due to the conjugation of C-C triple bond and inductive effect of electron-withdrawing group,ynamides achieve a perfect balance between reactivity and stability,and also show very good regioselectivity in different reactions.With the vigorous development of the field,ynamindes are more and more used in the synthesis of natural products and drug molecules.As a very useful structural unit,the applications of ynamides in organic synthesis are very extensive.For example,our laboratory has reported that ynamides are involved in the synthesis of many compounds such as 2-aminonaphthalenes,2-aminoanthrenes,2,4-diaminopyridines,4-aminopyrimidines,2-aminochromones and 3-aminoisocoumarins.According to our past accumulated experience and a large number of literatures investigation,enamides have been widely used in organic synthesis and a variety of natural products,which is of great significance for the construction of some important structural compounds.Despite a diverse array of oxygen nucleophile additions that have been developed,the hydroalkoxylation of ynamides which directly provides useful alkoxy-substituted enamides has met with limited success.Therefore,exploring more moderate and highly efficient synthetic methods is crucial and is also of great significance for practical application.In this dissertation,we present a highly efficient methodology of constructing alkoxy-substituted enamides via TMSOTf-catalyzed hydroalkoxylation of ynamides with esters under mild conditions,various ynamides are transformed into their corresponding enamides within short reaction times,and this method has the advantages of high yields,stereoselectivity and wide substrates scope.More importantly,this strategy first realized the metal-free hydroalkoxylation of ynamides for the synthesis of alkoxy-substituted enamides.In summary,this method provides a novel and efficient method for the synthesis of enamides.