Scholarly Work - Chemistry & Biochemistry

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    Mechanistic Origin of Ligand Effects on Exhaustive Functionalization During Pd-Catalyzed Cross-Coupling of Dihaloarenes
    (American Chemical Society, 2024-04) Larson, Nathaniel G.; Norman, Jacob P.; Neufeldt, Sharon
    We describe a detailed investigation into why bulky ligands─those that enable catalysis at “12e–” Pd0─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 π system of the nascent product. Selectivity for mono- vs difunctionalization arises from the relative rates of π-decomplexation versus a second oxidative addition. Under the Suzuki coupling conditions in this work, direct dissociation of 12e– PdL from the π-complex cannot outcompete oxidative addition. Instead, Pd must be displaced from the π-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 π-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.
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