Fluorine moieties are known to enhance the biological activities of organic compounds, hence, they are present in about 25 % of currently marketed pharmaceuticals and 40 % of agrochemicals. The late-stage introduction of fluorinated moieties into functionalized molecules is both challenging and highly desirable.
Lukas J. Goossen and colleagues, Technische Universität Kaiserslautern, Germany, have developed copper-catalyzed Sandmeyer-type processes for the generation of trifluoromethyl thio- and selenoethers from easily available aromatic amines. Reactions were carried out at room temperature and Me4NSCF3 and Me4NSeCF3 were used as the trifluoromethylation sources. The diazonium salts used for the coupling were easily generated by the reaction of anilines with tert-butyl nitrites in the presence of p-toluenesulfonic acid. The researchers propose that the process involves a classical Sandmeyer-type single-electron transfer (SET) mechanism via aryl radicals.
The reactions gave high yields and the process was usable on a gram scale. Various common functionalities such as cyano, amino, nitro, and keto groups were well tolerated. The key advantages of this methodology are the mild reaction conditions, the use of an inexpensive Cu catalyst, and the exceptional functional group tolerance.
- Sandmeyer-Type Trifluoromethylthiolation and Trifluoromethylselenolation of (Hetero)Aromatic Amines Catalyzed by Copper,
Christian Matheis, Victoria Wagner, Lukas J. Goossen,
Chem. Eur. J. 2015.