Unveiling mechanistic patterns of copper-catalyzed radical bond formation through linear free energy relationship

Copper-catalyzed radical transformations have seen extensive investigations over recent decades. Due to the complexity of controlling factors and the diversity of reaction components, accurately delineating the bond formation mechanisms-namely reductive elimination, outer-sphere radical substitution, and ion pair-type bond formation-poses a formidable challenge. This study reveals the linear free energy relationships (LFER) for the C-C bond formation of Cu-catalyzed radical transformations. Leveraging this discovery, we formulate an accurate LFER model for predicting radical bond formation mechanisms in this catalytic system. By establishing LFER scales for ligands, radicals, and nucleophiles, the bond formation mechanisms across 132,300 potential Cu-catalyzed radical transformations are revealed, offering a detailed mechanistic guide for future C-C bond designs. This research advances the mechanistic understanding of Cu-catalyzed radical transformations, providing systematic and quantitative insights into the mechanistic preference of radical bond formations.