Catalytic C−C Coupling Reactions at Nickel by C−F Activation of a Pyrimidine in the Presence of a C−Cl Bond: The Crucial Role of Highly Reactive Fluoro Complexes

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.