Cationic Cyclization of 1,6-Enynes for the Synthesis of Methylene Glutarimides

Based on glutarimide's excellent phamaceutical bioactivities, herein, we developed a Brønsted acid-mediated cationic cyclization reaction of 1,6-enynes with electron-deficient alkyne as terminator. And the substrates can be easily transformed into diversified methylene glutarimides with tetrasubstituted alkenes in moderate to excellent yields. Furthermore, nucleophile scope can be diversified to include not only halides and O-nucleophiles, but also C-nucleophiles and S-nucleophiles. Moreover, this protocol demonstrates operational simplicity, mild reaction conditions, broad substrate scope, and gram-scale synthesis capability.