Work

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

Year: 2024

Type: article

Abstract: We describe a detailed investigation into why bulky ligands─those that enable catalysis at “12 e – ” Pd 0 ─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 12 e – PdL from the π-complex cannot outcompete oxidative addition. Instead, Pd must be displaced from the π-complex as 14 e – 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 14 e – 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.

Source: ACS Catalysis

DOI: 10.1021/acscatal.4c00646

Authors: Nathaniel G. Larson, Jacob P. Norman, Sharon R. Neufeldt

Institution: Montana State University

Language: English

Topic: Catalytic Cross-Coupling Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences, Office of Advanced Cyberinfrastructure, Division of Chemistry