C3–H Trifluoroacetylation of Quinolines and Pyridines: Access to Heteroaryl Ketones, Carboxylic Acids, and Amides

Abstract

Despite extensive synthetic endeavors, achieving direct C3-H trifluoroacetylation in quinolines/pyridines continues to pose significant challenges. We report a protocol for direct C3-H trifluoroacetylation of quinolines and pyridines under transition-metal-free conditions. Readily accessible quinolines or pyridines serve as starting materials and undergo a dearomatization process to generate dihydroquinoline or dihydropyridine intermediates, which readily react with trifluoracetic anhydride. Subsequent acid-promoted dealkylative rearomatization delivers heteroaryl trifluoromethyl ketones. This tandem process is accomplished in a two-pot, one column process. The trifluoroacetyl group in the resulting heteroarenes can be readily transformed into a variety of functional groups.