Fluorine meets amides

Abstract

There’s a silver lining for chemists trying to make N-trifluoromethyl carbonyl compounds. Using silver fluoride as a key reagent, a team at RWTH Aachen University has developed a general method for making these elusive compounds, including N-trifluoromethyl amides, carbamates, thiocarbamates, and ureas (Nature 2019, DOI: 10.1038/s41586-019-1518-3). The reaction could help medicinal chemists on the hunt for new drugs. These chemists often incorporate amides into their drug candidates because the motif can help a compound bind to its biological target. As a result, amides show up frequently in best-selling small-molecule drugs. But amides are also sites where the body’s enzymes can metabolize drug molecules. If chemists could add a trifluoromethyl group—which tends to resist biological breakdown—to an amide’s nitrogen, they might be able to make a drug last longer in the body. Until now, making these N-trifluoromethyl amides has been tricky. Such reactions required toxic or extremely reactive reagents, like...