Opening a Pandora's Flask on a Prototype Catalytic Direct Arylation Reaction of Pentafluorobenzene: The...

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 PPh₃ ligand, silver carbonate as base, and DMF as solvent. By studying the reaction of 1 with Ag₂CO₃/PPh₃ and with isolated silver (triphenylphosphine) carbonate complexes, we show the formation of C-H activation products containing the Ag(C₆F₅)(PPh₃)_n unit. However, analysis is complicated by the lability of the Ag-PPh₃ 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)(κ¹-OAc)(PPh₃)₂ and [Pd(Ar)(μ-OAc)(PPh₃)]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/nPPh₃]^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(PPh₃)₄, Pd(Ph)(κ¹-OAc)(PPh₃)₂, and [Pd(Ph)(μ-OAc)(PPh₃)]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.