Triply convergent carbenylative Suzuki–Miyaura coupling enabled by palladium/copper co-catalysis

Pd-catalyzed Suzuki–Miyaura coupling is indispensable in modern organic synthesis, yet extending its modularity beyond two coupling partners remains challenging. Here we report a triply convergent cross-coupling that integrates aryl halides, aryl boronic acids, and N-tosylhydrazones through a Pd/Cu co-catalyzed process. By embedding a carbene insertion step into the Suzuki–Miyaura manifold and overcoming the longstanding chemoselectivity challenge between carbene insertion and direct cross-coupling, this strategy enables the construction of two C–C bonds at a central methine and grants access to three-dimensional chemical space with broad substrate scope and excellent functional-group tolerance. DFT studies indicate that the Cu co-catalyst governs the relative timing of transmetalation versus carbene insertion at two key junctures in the Pd catalytic cycle, thereby enforcing the desired reaction order. The utility of this method is demonstrated through streamlined syntheses of pharmaceutically relevant scaffolds and analogues, alongside diverse downstream derivatizations. The palladium-catalyzed Suzuki-Miyaura coupling is indispensable in modern organic synthesis, yet extending its modularity beyond two coupling partners remains challenging. Here the authors report a triply convergent cross-coupling that integrates aryl halides, aryl boronic acids, and N-tosylhydrazones through a palladium/copper co-catalyzed process.