Opening a Pandora's Flask on a Prototype Catalytic Direct Arylation Reaction of Pentafluorobenzene: The Ag 2 CO 3 /Pd(OAc) 2 /PPh 3 System.

Direct C-H functionalization reactions have opened new avenues in catalysis, removing the need for prefunctionalization of at least one of the substrates. Although C-H functionalization catalyzed by palladium complexes in the presence of a base is generally considered to proceed by the CMD/AMLA-6 mechanism, recent research has shown that silver(I) salts, frequently used as bases, can function as C-H bond activators instead of (or in addition to) palladium(II). In this study, we examine the coupling of pentafluorobenzene 1 to 4-iodotoluene 2a (and its analogues) to form 4-(pentafluorophenyl)toluene 3a catalyzed by palladium(II) acetate with the commonplace PPh 3 ligand, silver carbonate as base, and DMF as solvent. By studying the reaction of 1 with Ag 2 CO 3 /PPh 3 and with isolated silver (triphenylphosphine) carbonate complexes, we show the formation of C-H activation products containing the Ag(C 6 F 5 )(PPh 3 ) n unit. However, analysis is complicated by the lability of the Ag-PPh 3 bond and the presence of multiple species in the solution. The speciation of palladium(II) is investigated by high-resolution-MAS NMR (chosen for its suitability for suspensions) with a substoichiometric catalyst, demonstrating the formation of an equilibrium mixture of Pd(Ar)(κ 1 -OAc)(PPh 3 ) 2 and [Pd(Ar)(μ-OAc)(PPh 3 )] 2 as resting states (Ar = Ph, 4-tolyl). These two complexes react stoichiometrically with 1 to form coupling products. The catalytic reaction kinetics is investigated by in situ IR spectroscopy revealing a two-term rate law and dependence on [Pd tot /nPPh 3 ] 0.5 consistent with the dissociation of an off-cycle palladium dimer. The first term is independent of [ 1 ], whereas the second term is first order in [ 1 ]. The observed rates are very similar with Pd(PPh 3 ) 4 , Pd(Ph)(κ 1 -OAc)(PPh 3 ) 2 , and [Pd(Ph)(μ-OAc)(PPh 3 )] 2 catalysts. The kinetic isotope effect varied significantly according to conditions. The multiple speciation of both Ag I and Pd II acts as a warning against specifying the catalytic cycles in detail. Moreover, the rapid dynamic interconversion of Ag I species creates a level of complexity that has not been appreciated previously.