Intramolecular hydrogen bonding in phenolic amides enables direct synthesis of indolizines

Abstract

Herein, pyridinium 1,4-zwitterionic thiolates were treated with various chloroacetamides to form indolizines. Intramolecular hydrogen bonding in phenolic amides guides a stepwise [(5 + 1) − 1] cyclization that allows for the mild and efficient synthesis of these compounds. DFT calculations provided detailed insights into crucial interactions and structural characteristics. The theoretical and practical results confirmed the significant impact of intramolecular hydrogen bonding on the activation of the α-CH₂ of the amide carbonyl group.