Mechanistic and Computational Studies of Oxidatively-Induced Aryl-CF3 Bond-Formation at Pd: Rational Design of Room Temperature Aryl Trifluoromethylation

This article describes the rational design of first generation systems for oxidatively induced Aryl-CF3 bond-forming reductive elimination from Pd-II. Treatment of (dtbpy)Pd-II(Aryl)(CF3) (dtbpy = di-tert-butylbipyridine) with NFTPT (N-fluoro-1,3,5-trimethylpyridinium triflate) afforded the isolable Pd-IV interrnediate (dtbpy)Pd-IV(Aryl)(CF3)(F)-(OTf). Thermolysis of this complex at 80 degrees C resulted in Aryl-CF3 bond-formation. Detailed experimental and computational mechanistic studies have been conducted to gain insights into the key reductive elimination step. Reductive elimination from this Pd-IV species proceeds via pre-equilibrium dissociation of TfO- followed by Aryl-CF3 coupling. DFT calculations reveal that the transition state for Aryl-CF3 bond formation involves the CF3 acting as an electrophile with the Aryl ligand serving as a nudeophilic coupling partner. These mechanistic considerations along with DFT calculations have facilitated the design of a second generation system utilizing the tmeda (N,N,N',N'-tetramethylethylenediamine) ligand in place of dtbpy. The tmeda complexes undergo oxidative trifluoromethylation at room temperature.