On-Cycle Enforcement in Water: Trimetallic Assemblies Preventing Pd Black Formation While Accelerating Selective Suzuki-Miyaura Coupling without Olefin Interference.

Palladium-catalyzed cross-couplings are frequently limited by off-cycle deactivation pathways, particularly phosphine deligation followed by aggregation of Pd(0) to catalytically inactive palladium black. We report an "on-cycle enforcement" strategy that employs a cooperative, nonalloyed trimetallic assemblyPd(0), Cu-(I), and Mn-(III)confined within PS-750-M/HPMC micelles in water. In this architecture, Pd mediates the canonical oxidative addition and reductive elimination steps, Cu-(I) accelerates transmetalation via a Cu-nucleophile intermediate, and Mn-(II/III) serves as a redox buffer that likely continuously reoxidizes off-cycle Pd(0) to micelle-soluble Pd-(II), followed by its religation and reduction, thereby preventing Pd black formation. Spectroscopic analysistransmission electron microscopy, scanning transmission electron microscopy-high-angle annular dark-field imaging, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and X-ray absorption spectroscopyreveals that the three metals remain spatially separated in the assembly yet electronically complementary within a phosphorus-rich matrix, enabling persistent catalytic activity. The resulting platform supports rapid, selective C-C couplings at 45 °C with broad substrate compatibility, including heteroarenes and terminal olefincontaining partners, without olefin interference. The catalyst displays exceptional longevity, minimal metal leaching (<1 ppm), and robust scalability, with multicycle reactions and gram-scale processes proceeding efficiently even after extended catalyst storage. These findings establish redox-buffered, compartmentalized trimetallic assemblies as a general solution to enforcing on-cycle Pd catalysis in water.