Catalyst Activation and Speciation Involving DyadPalladate™ Pre-Catalysts in Suzuki-Miyaura and Buchwald-Hartwig Cross-Couplings

Understanding mechanisms underpinning Pd pre-catalyst activation and formation of active species is important in maximizing catalyst activity and lifetime. DyadPalladateTM pre-catalysts, represented by the general formula [R3PH+]2[Pd2Cl6]2– (R3P = tertiary alkylphosphine/arylphosphines), have recently emerged as sustainable, active Pd pre-catalysts 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 pre-catalyst from the DyadPalladateTM class, against BHA and SMCC reactions. It was found that BHA and SMCC reactions reach 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 was compared with known PdII pre-catalysts, possessing the XPhos ligand, through both stoichiometric and catalytic studies. Investigating the activation triggers and characterizing the active Pd0 catalyst, under catalytically relevant conditions, provides valuable insight into future catalyst design, targeting optimal efficiency in specific reactions, i.e. knowing that the pre-catalyst has been fully activated