Mechanistic and Experimental Insights into Ligand-Class and Radical-Identity Effects on S_H2-Mediated Radical Sorting...

Herein, we report a detailed mechanistic and experimental investigation of the nickel-catalyzed bimolecular homolytic substitution (S_H2) reaction, with an emphasis on how the ligand environment influences the individual steps of the catalytic cycle. Using Ni-catalyzed difunctionalization as a model, density functional theory (DFT) calculations were performed to gain insight into the origins of selectivity in the initial radical capture and the subsequent S_H2-mediated radical sorting process. These calculations suggest clear differences between anionic and neutral ligand systems. For the anionic Ni-(Tp^*)(acac) catalyst, the reaction proceeds efficiently through an open-shell singlet S_H2 pathway, wherein the ligand's steric bulk and electron-rich character promote radical capture while disfavoring competing pathways. In contrast, the neutral Ni-bpy system favors a triplet S_H2 pathway with a significantly higher barrier and is subject to intense competition from multiple low-energy hydrogen-transfer pathways. Furthermore, the mechanistic framework is extended to more sterically demanding 2°-3° and 3°-3° couplings, identifying hydrogen-transfer pathways as a key challenge. Collectively, this work supports a unified mechanistic picture of Ni-catalyzed S_H2 reactions and provides a rational basis for ligand design to achieve efficient and selective radical cross-couplings, particularly in congested systems.