Efficient Synthesis of Medium-sized Nitrogen Heterocycles by Bronsted Acid-Catalyzed Cyclization of Ene-ynamides

A Bronsted acid-catalysed cyclization of ene-ynamides has been developed to construct 7- or 8-membered azacycles in good to high yields. The use of a simple C=C double bond as a nucleophile enables the synthesis of medium-sized ring from an acyclic ynamide. This reaction system features simple and mild reaction conditions without any metal catalysts, and no requirement of high dilution for medium-sized ring formation. This method is applicable to a variety of substituents on the ynamides, such as alkyl, aryl, acetylene and silyloxy group.

Automated summary

A Bronsted acid-catalysed cyclization of ene-ynamides has been developed for the synthesis of 7- or 8-membered azacycles in good to high yields. This method utilizes a simple C=C double bond as a nucleophile to form medium-sized rings from acyclic ynamides. The reaction conditions are mild and do not require the use of metal catalysts or high dilution for medium-sized ring formation. Various substituents, including alkyl, aryl, acetylene, and silyloxy groups, can be accommodated in this reaction system.