Mechanistic Origin of Ligand Effects on Exhaustive Functionalization During Pd-Catalyzed Cross-Coupling of Dihaloarenes

We describe a detailed investigation into why bulky ligands & horbar;those that enable catalysis at "12e(-)" Pd-0 & horbar;tend to promote overfunctionalization during Pd-catalyzed cross-couplings of dihalogenated substrates. After one cross-coupling event takes place, PdL initially remains coordinated to the pi system of the nascent product. Selectivity for mono- vs difunctionalization arises from the relative rates of pi-decomplexation versus a second oxidative addition. Under the Suzuki coupling conditions in this work, direct dissociation of 12e(-) PdL from the pi-complex cannot outcompete oxidative addition. Instead, Pd must be displaced from the pi-complex as 14e(-) PdL(L') by a second incoming ligand L'. The incoming ligand is another molecule of dichloroarene if the reaction conditions do not include pi-coordinating solvents or additives. More overfunctionalization tends to result when increased ligand or substrate sterics raises the energy of the bimolecular transition state for separating 14e(-) PdL(L') from the monocross-coupled product. This work has practical implications for optimizing the selectivity in cross-couplings involving multiple halogens. For example, we demonstrate that small coordinating additives like DMSO can largely suppress overfunctionalization and that the precatalyst structure can also impact selectivity.