Golden ticket to trifluoromethylations

Abstract

Medicinal chemists love to add trifluoromethyl groups to drug candidates. The substituents are roughly the size of a milquetoast methyl, but the C–F bonds make the moieties resistant to metabolism, helping compounds to circulate longer in the body. Now, chemists led by F. Dean Toste at the University of California, Berkeley, report a new method for adding trifluoromethyl substituents to molecules. Working in collaboration with researchers at Lawrence Berkeley National Laboratory, led by James P. O’Neil, the chemists adapted the reaction to make molecules with one 18F in the trifluoromethyl group, creating a new method for making radiolabeled compounds for positron emission tomography (PET). The reaction uses a tris(pentafluorophenyl)borane catalyst and stoichiometric amounts of a gold complex to generate the trifluoromethylated product (Science 2017, DOI: 10.1126/science.aan1411). The gold complex tolerates a wide range of reactions, including aluminum hydride reduction, Simmons-Smith cyclopropanation, os...