DFT Insights into Pd-Catalyzed Aminative Suzuki-Miyaura Coupling for Diarylamine Synthesis

A recently developed transformation merges features of Suzuki-Miyaura and Buchwald-Hartwig couplings by introducing formal nitrene insertion, thereby redirecting the reaction outcome from C-C-linked biaryls to C-N-C-linked diarylamines (Science, 2024, 383, 1019). In this work, density functional theory (DFT) calculations are employed to elucidate the reaction mechanism and the ligand-controlled origin of the selectivity. The results clarify that the reaction proceeds via a nucleophile-first pathway rather than an electrophile-first pathway, resolving a key mechanistic ambiguity left open by the experimental study. Moreover, the calculations highlight the pivotal role of the ligand in governing product selectivity. The t-BuBrettPhos ligand stabilizes the C-N bond-forming transition state via C-H···π interactions with the substrate, favoring diarylamine formation. In contrast, the RuPhos ligand promotes C-C bond formation due to its intrinsically reduced steric bulk and electron-deficient nature, leading to the biphenyl product. These findings offer molecular-level insights into the elegant aminative Suzuki-Miyaura coupling strategy and its ligand-controlled pathway selectivity, providing a theoretical foundation for the rational design of catalysts with improved efficiency.