TsCl-Mediated, Copper-Catalyzed Deoxygenative Difluoromethoxylation Reaction of Quinoline- N -Oxides

Abstract

Abstract Quinoline derivatives have played a pivotal role in the design and synthesis of drug-active substances and bioactive molecules for a long time. Herein, a TsCl-mediated, copper-catalyzed deoxygenative difluoromethoxylation reaction that facilitates the synthesis of 2-difluoromethoxy quinoline derivatives in good to excellent yields is described. In this method, quinoline-N-oxides are utilized as substrates and ethyl bromodifluoroacetate as a difluoromethylation reagent. The reaction mechanism has been explored, revealing that the oxygen atom of the products originates from water in the reaction system. The advantages of this method include its simplicity, environmental friendliness, and efficiency.