Regioselective TfOH-mediated Hydroamidation Of Ynamides With Nitriles

In organic synthesis,enamides derivatives,a fundamental sort of compounds,have been proved to be the elemental,significant,and versatile building blocks in organic synthesis,as well as a skeletal part of the massive and diverse natural products and compounds with pharmacological activity.For example,enamides have been widely used to construct chiral amino derivatives or nitrogen heterocyclic frameworks,such as pyridines,pyrimidines,and isoquinolines.To the best of our current knowledge,the conventional preparative methods mainly depend on direct addition of amides to alkynes,the coupling reaction ofamides with olefin,and acylation of imines.However,these protocols suffered from low yields,high temperature or metel as catalysts.Thus,the development of novel approaches,especially as part of functionalized scaffolds with high efficiency,flexibility,and good regioselectivity,remains an urgent and challenging synthetic goal.In this paper,a rapid and efficient method for the preparation of enamides was developed,which was based on the Tf OH as catalyst and ynamides as substrates.Features of this reaction include:1)mild reaction conditionswithout high temperature;2)water as a reaction component,green and environmentfriendly;3)the substrates had a wide range of adaptability;4)further chemical transformation of the as synthesized enamideswere also explored.A variety of enamides were prepared from ynamides in the presence of trifluoromethanesulfonic acidthroughketenimine ion intermediates,followed by tandem reaction with nitriles and water.All compounds had been confirmed by ¹H NMR,¹³C NMR,MS and HR-MS.And the enamides reacted with nitriles or alkynes to further generate highly substituted pyridine,4-aminopyrimidine or isoquinoline cores.