Synthesis of Nitrogen-containing Heterocycles Using Ynamides and their Application to Natural Products

Heterocycles are an important and attractive class of compounds for medicinal and material chemistries because of their biological importance and structural features. Meanwhile, ynamides have received much attention as fascinating building blocks for the synthesis of nitrogen-containing compounds because of their availability and unique reactivity. In particular, the ring-forming reactions of ynamide are an efficient and atom-economical method for the synthesis of nitrogen-containing cyclic molecules. In the review, we introduce our recent transformations of ynamides with acid catalysts to construct heterocyclic compounds. First, we demonstrated Brønsted acid promoted arene-ynamide cyclization to construct multicyclic quinolines toward the total synthesis of marinoquinolines and aplisiopsamine A. Moreover, Lewis acid catalyzed diastereoselective domino reaction of ene-ynamide with external nucleophiles to yield spiroindolopyrrolidine derivatives was developed. Finally, we demonstrated efficient synthesis of medium-sized nitrogen heterocycles by Brønsted acid-catalyzed cyclization of ene-ynamides.