Nickel and Palladium Catalyzed C−H Trifluoromethylation using Trifluoromethyliodide: Investigations into New Reactivity

Due to the prevalence of the trifluoromethyl group (CF3) in high-value organic compounds, there is a constant demand for more selective, efficient and economical trifluoromethylation strategies. In this report we present detailed experimental and computational investigations into the use of cheap and atom-economical CF3I in transition metal catalyzed trifluoromethylation. The mechanistic insight gained allowed novel C−H trifluoromethylation processes to be developed, using both palladium and nickel catalysis. The reported methodology is remarkably selective for C−H trifluoromethylation, with substituents such as amino, nitro, bromo and aldehydes tolerated. Our experimental and computational studies suggest that radical species are not involved, and that the key C−H activation step is facilitated by an unusual difluorocarbene intermediate. Importantly, arylCF3 formation occurs through unique arylCF2-F based reductive elimination, likely from Pd(II)/Ni(II) but potentially through oxidatively-induced reductive elimination from Pd(IV)/Ni(IV). This is the first example of nickel-mediated trifluoromethylation where reductive elimination from nickel can occur in a catalytic manner.