The first to investigate trifluoromethyl groups in relationship to biological activity was F. Lehmann in 1927. An early review appeared in 1958. An early synthetic method was developed by Frédéric Swarts in 1892, based on antimony fluoride. In this reaction benzotrichloride was reacted with SbF to form PhCFCl and
PhCF. In the 1930s Kinetic Chemicals and IG Farben replaced SbF with HF.
The McLoughlin-Thrower reaction (1968) is an early coupling reaction using iodofluoroalkanes, iodoaromatic compounds and copper. In 1969 Kobayashi & Kumadaki adapted their protocol for trifluoromethylations.