Effects of PAr3 Ligands on Direct Arylation of Heteroarenes with Isolated [Pd(2,6-Me2C6H3)(μ‑O2CMe)(PAr3)]4 Complexes

The palladium-catalyzed direct arylation of heteroarenes with aryl halides has attracted considerable attention as a simple cross-coupling process that does not need organometallic reagents. It is generally accepted that this catalysis proceeds via an arylpalladium carboxylate intermediate, which produces direct arylation products via the sequence of three elementary processes: (a) substrate coordination, (b) C–H bond cleavage, and (c) C–C reductive elimination. This paper describes kinetic investigations into the effects of four kinds of PAr3 ligands on direct arylation using the isolated complexes [Pd­(2,6-Me2C6H3)­(μ-O2CMe)­(PAr3)]4 (1: Ar = Ph (a), 4-MeOC6H4 (b), 4-FC6H4 (c), 4-F3CC6H4 (d)). While 1a–d have a tetrameric structure in the solid state, they are in rapid equilibrium with the monomeric species [Pd­(2,6-Me2C6H3)­(O2CMe-κ2O)­(PAr3)] in solution. Complexes 1a–d react with 2-methylthiophene (3) and benzothiazole (4) in THF at 65 °C to give the corresponding direct arylation products in high yields. The reactivity order of 1a–d is reversed according to the heteroarene substrates; the reaction with 3 is accelerated by electron-deficient PAr3 (1b 1a 1c 1d), whereas that with 4 is facilitated by electron-donating PAr3 (1d 1c 1a 1b). The reasons for the opposite ligand effects are examined by DFT calculations using the model compounds [PdPh­(O2CMe-κ2O)­(PAr3)]. Unlike the general assumption, the C–H bond cleavage process is relatively insensitive to electronic properties of PAr3. Instead, the reaction of 3 invokes the C–C reductive elimination process as the rate-determining step, and the activation energy is significantly reduced by electron-deficient PAr3. On the other hand, although the rate-determining step for 4 is assigned to the C–H bond cleavage process, the transition state is little affected by PAr3 ligands. In this case, electron-donating PAr3 destabilizes the precursor complex for C–H bond cleavage, thereby reducing the activation barrier for the rate-determining step.