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

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.