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 π-acidic properties
has remained significantly underexplored. Herein, we demonstrate that
well-defined and low-coordinate Pd0 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 °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 PdII monoisocyanide PdCl­(η3-C3H5)­(CNArDipp2) with alkoxide base yielded the dinuclear
PdI species (μ-C3H5)­(μ-OiPr)­[Pd­(CNArDipp2)]2. Although dinuclear PdI complexes are often produced
as off-cycle species when using complexes of the type PdCl­(η3-allyl)­L as precatalysts, this represents the first time that
the comproportionation product (μ-allyl)­(μ-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 β-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 Pd3(η2-Dipp-μ-CNArDipp2)3. This cluster is catalytically competent for the Suzuki–Miyaura
reaction and functions as a formal source of monoligated Pd­(CNArDipp2) in solution.