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

Abstract

AbstractDue 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.