Mechanistic understanding of the Cu(i)-catalyzed domino reaction constructing 1-aryl-1,2,3-triazole from electron-rich aryl bromide, alkyne, and sodium azide: a DFT study

The mechanism of the Cu(i)-catalyzed domino reaction furnishing 1-aryl-1,2,3-triazole assisted by CuI and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is explored with density functional theory (DFT) calculations. The overall mechanism for this domino reaction comprises four consecutive reactions: (i) deprotonation of terminal alkyne by DBU; (ii) cycloaddition of copper acetylide and N-3(-); (iii) C-N bond coupling of the cuprate-triazole anion and aryl bromide; and (iv) protodecupration. Our theoretical calculations indicate that the Cu-catalyzed azidation of the electron-rich aryl bromides with N-3(-), which would generate the aryl azide for subsequent Cu(i)-catalyzed alkyne-azide cycloaddition, is not the dominant reaction because of its high free energy barrier. In addition, the cycloaddition process can assist C(aryl)-N bond formation. Activation strain analyses suggest that oxidative addition of aryl bromide onto the cuprate-triazole anion is more facile mainly due to enhanced d(Cu)- orbital interaction. A close attraction between copper and aryl bromide during oxidative addition is critical to the lower barrier.

Automated summary

The mechanism of Cu(I)-catalyzed domino reaction for synthesizing 1-aryl-1,2,3-triazole was investigated using DFT calculations, revealing four consecutive reactions and highlighting the importance of aryl azide formation and C-N bond coupling steps. Enhanced d(Cu)- orbital interaction plays a crucial role in the oxidative addition of aryl bromide onto cuprate-triazole anion, lowering the energy barrier.