Treatment of [Ni(COD)₂] (COD = 1,5-cyclooctadiene) with 5-chloro-2,4,6-trifluoropyrimidine (1) in the presence of PⁱPr₃ or PPh₃ effects the formation of the fluoro complexes trans-[NiF(4-C₄N₂ClF₂)(PⁱPr₃)₂] (3) and trans-[NiF(4-C₄N₂ClF₂)(PPh₃)₂] (4). The chloro complex trans-[NiCl(4-C₄N₂ClF₂)(PPh₃)₂] (5) can be prepared by reaction of 4 with Me₃SiCl. In contrast, a reaction of 1 with [Pd(PPh₃)₄] leads to the insertion of a {Pd(PPh₃)₂} unit into the C−Cl bond yielding trans-[PdCl(5-C₄N₂F₃)(PPh₃)₂] (6). Treatment of 4 with an excess of TolB(OH)₂ at 273 K results in the slow formation of trans-[NiF(4-C₄N₂TolClF)(PPh₃)₂] (7) and subsequently 5-chloro-2-fluoro-4,6-ditolylpyrimidine (8). Quenching of a solution of 7 with Me₃SiCl leads to the chloro derivative trans-[NiCl(4-C₄N₂TolClF)(PPh₃)₂] (9). Treatment of 4 with PhB(OH)₂ followed by addition of Me₃SiCl gives the complex trans-[NiCl(4-C₄N₂PhClF)(PPh₃)₂] (10). In catalytic experiments, 1 is converted with the boronic acids TolB(OH)₂, PhB(OH)₂, and p-F₃CC₆H₄B(OH)₂ into the 5-chloro-2-fluoro-4,6-diarylpyrimidines 8, 11, and 12 in 73%, 88%, and 37% yield, respectively, when 10% of 4 is employed as catalyst. The molecular structures of the complexes 5, 6, and 10 have been determined by X-ray crystallography. The studies reported in this paper represent the first catalytic C−C coupling reactions involving the activation of a C−F bond in the presence of a thermodynamically weaker C−Cl bond. They provide a route to access 5-chloro-2-fluoro-4,6-diarylpyrimidines, which have not been described before. There is considerable evidence that the presence of the fluoro ligand in 4 is crucial for the transmetalation step to occur and for the catalytic cycle to proceed.