Zirconium Oxide‐Catalyzed Direct Amidation of Unactivated Esters under Continuous‐Flow Conditions

A sustainable and environmentally benign direct amidation reaction of unactivated esters with amines has been developed in a continuous‐flow system. A commercially available amorphous zirconium oxide was found to be an efficient catalyst for this reaction. While the typical amidation of esters with amines requires a stoichiometric amount of a promoter or metal activator, the present continuous‐flow method enabled the direct amidation reaction under additive‐free conditions with an extensive diversity towards various functional groups. High yields of the products were obtained with a nearly equimolar proportion of starting materials to reduce byproduct formation, which renders this process applicable for use in a sequential‐flow system.