Catalyst Activation and Speciation Involving DyadPalladate Precatalysts in Suzuki-Miyaura and Buchwald-Hartwig Cross-Couplings

Understanding mechanisms underpinning Pd precatalyst activation and formation of active species is important in maximizing catalyst activity and lifetime. DyadPalladate precatalysts, represented by the general formula [R3PH+]2[Pd2Cl6]2- (R3P = tertiary alkylphosphine/arylphosphines), have recently emerged as sustainable, active Pd precatalysts for cross-couplings (e.g., Suzuki-Miyaura {SMCC} and Buchwald-Hartwig aryl amination {BHA}). This study investigates the activation of the [HXPhos]2[Pd2Cl6] 1, as a model precatalyst from the DyadPalladate class, against BHA and SMCC reactions. It was found that BHA and SMCC reactions reached the same active Pd0 catalyst, [Pd0(XPhos)2]. This species is generated efficiently through a reductive activation step involving a dual base/nucleophile chemical trigger. However, the mechanistic path of each is somewhat different based on the selected nucleophile. The active Pd complex participates in oxidative addition with aryl halides, the first committed step in many cross-coupling reactions. The activation pathway and catalytic efficiency of [HXPhos]2[Pd2Cl6] 1 were compared with those of known PdII precatalysts, possessing the XPhos ligand, through both stoichiometric and catalytic studies. Investigating the activation triggers and characterizing the active Pd0 catalyst, under catalytically relevant conditions, provide valuable insight into future catalyst design, targeting optimal efficiency in specific reactions, i.e., knowing that the precatalyst has been fully activated.