Metal-free stereoselective addition of propiolic acids to ynamides: a concise synthetic route to highly substituted enediyne/dienyne-(E)-N,O-acetals

Abstract

A straightforward and sustainable approach for the 1,2-addition of propiolic acids to ynamide has led to bench-stable sp² (E)-enol-enamides of enediynes and dienynes. The reaction is chemo-, regio-, and stereoselective and does not require metal catalysts and solvent. The ynamide motif is extremely amenable to functionalization in the presence of the tethered alkyne triple bond. The synthetic technique is operationally simple; no hydrolysis of ketenimine species occurs under acidic conditions. The transformation tolerates a wide range of common functional groups, constructing a library of highly functionalized 1,5,5′/6′-enediynes and 1,5,5′-dienynes of sp² (E)-N,O-acetal skeletons.