Synthetic and Mechanistic Interrogation of Pd/Isocyanide-Catalyzed Cross-Coupling: π-Acidic Ligands Enable Self-Aggregating Monoligated Pd(0) Intermediates

Despite the large number of judiciously designed ligands that have been exploited in palladium-catalyzed cross-coupling protocols, the incorporation of ligands bearing appreciable pi-acidic properties has remained significantly underexplored. Herein, we demonstrate that well-defined and low-coordinate Pd-0 complexes supported by m-terphenyl isocyanides function as competent catalysts for the Suzuki Miyaura cross-coupling of aryl bromides and arylboronic acids. Two-coordinate Pd(CNArDiPP2)(2) was active for the coupling of unhindered aryl bromides at room temperature in 2-propanol, while increasing the temperature to 60 degrees C allowed for the use of mono-or di-ortho-substituted aryl bromides. Oxidative addition of the aryl bromide was shown to proceed via a dissociative mechanism, implicating monoligated Pd(CNArDipp2) as the catalytically active intermediate. Attempts to access this fleeting species via activation of the Pd-II monoisocyanide PdCl(eta(3)-C3H5)(CNArDipp2) with alkoxide base yielded the dinuclear Pd-I species mu-C3H5(mu-O'Pr)[Pd(CNArDipp2)](2). Although dinuclear Pd-I complexes are often produced as off-cycle species when using complexes of the type PdCl(eta(3)-allyl)L as precatalysts, this represents the first time that the comproportionation product (mu-allyl)(mu-Cl)[PdL](2) has been observed to undergo nucleophilic substitution with alkoxide, despite the fact that activating conditions for these precatalysts typically employ alkoxide bases. Remarkably, this alkoxide complex can undergo, beta-hydride elimination with expulsion of acetone and propene to produce two equivalents of, catalytically active Pd(CNArDipp2), which can self-aggregate to yield the isolable tripalladium cluster Pd-3(eta(2)-Dipp-mu-CNArDipp2)(3). This cluster is catalytically competent for the Suzuki Miyaura reaction and functions as a formal source of monoligated Pd(CNArDipp2) in solution.