Ligand Effects of BrettPhos and RuPhos on Rate-Limiting Steps in Buchwald–Hartwig Amination Reaction Due to the Modulation of Steric Hindrance and Electronic Structure

[Image: see text] The differences in catalytic activity between two catalyst ligands of Buchwald–Hartwig amination reaction, BrettPhos versus RuPhos, were investigated using density functional theory (DFT) calculations. The reaction process consists of three consecutive steps: (1) oxidative addition, (2) deprotonation, and (3) reductive elimination. Among them, the rate-limiting step of Pd-BrettPhos catalytic system is oxidative addition but that of Pd-RuPhos catalytic system is reductive elimination due to their differences in steric hindrance and electronic structure. It was also revealed that amines with large-size substituents or halides with electron-withdrawing groups would reduce the activation energy barriers of the reactions. The insights gained from the calculations of the Buchwald–Hartwig amination reaction would be helpful for the rational designing of new catalysts and reactions.