Trifluoromethylation Meets Flow Chemistry

When chemists want to tweak the properties of an aromatic or heteroaromatic molecule, they often gussy it up with a trifluoromethyl group. The CF₃ substituent is known to alter solubility and improve the activity of drugs. There are several ways to append CF₃ groups to the rings, but no existing process is without its flaws. Some produce a variety of regioisomers. Others require reagents that are tricky to work with. Seeking to provide chemists with a simple and scalable trifluoromethylation method, MIT chemists Stephen L. Buchwald and Mao Chen combined their expertise in trifluoromethylation with their know-how in flow chemistry, where reactions are run via a continuous stream instead of in a batch. They’ve come up with a process that can make trifluoromethylated aromatics and heteroaromatics in a matter of minutes (Angew. Chem. Int. Ed. 2013, DOI: 10.1002/anie.201306094). The copper-mediated cross-coupling reaction uses aryl iodides as starting materials and inexpensive and easy-to-handle potassium trifluoroacetate as a CF₃ source.