Larson, Nathaniel G.Norman, Jacob P.Neufeldt, Sharon2024-08-292024-08-292024-04Larson, N. G., Norman, J. P., & Neufeldt, S. R. (2024). Mechanistic Origin of Ligand Effects on Exhaustive Functionalization During Pd-Catalyzed Cross-Coupling of Dihaloarenes. ACS Catalysis, 14(9), 7127-7135.2155-5435https://scholarworks.montana.edu/handle/1/18790We 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.en-USCopyright American Chemical Society 2024http://web.archive.org/web/20190502075603/http://pubs.acs.org/paragonplus/copyright/jpa_form_a.pdfTECHNOLOGY::Chemical engineering::Chemical process and manufacturing engineering::Catalysisoxidative additiondifunctionalizationligand effectsring-walking12-electron palladiumArticle10.1021/acscatal.4c00646