Versatile Catalyst Delivers CF₃ Groups

Tack one more reaction onto the list that bulky ligands from MIT help accomplish—adding tri­fluo­ro­meth­yl groups to aromatic rings. Tri­fluo­ro­meth­yls make molecules more lipophilic and metabolically stable, among other desirable properties, so chemists in the drug and agrochemical industries are constantly trying to prepare them more efficiently. Stephen L. Buchwald and colleagues at MIT previously used a bulky, phosphine-containing ligand to install fluorine atoms on aromatic rings (C&EN, Aug. 17, 2009, page 7). Now, they’ve applied a related ligand to trifluoromethylations, with help from a catalytic amount of palladium and a silicon reagent that acts as a trifluoromethyl source (Science 2010, 328, 1679). So far, the reaction (shown) works best at elevated temperatures. But it doesn’t require directing groups, and it works with a wide range of aryl chlorides, including heteroaromatic chlorides. The work is “one of the most important breakthroughs in fluoroalkylation chemistry since the late 1960s,” says David A. Vicic, an organometallic chemist at the University of Hawaii, Manoa. “The future of this chemistry will be to get the reactions to go using cheaper reagents,” he adds.