Computational study of Ru-catalyzed cycloisomerization of 2-alkynylanilides

The reaction mechanism of Ru-catalyzed cycloisomerization of 2-alkynylanilides to 3-substituted indole or 2-substituted indole was analyzed at the B3LYP level of density functional theory. The solvation effect of the system was also considered by SMD model. The calculation results show that the reaction system first forms a ruthenium π-alkyne complex. On the one hand, the cyclization reaction of the amino group and the alkyne carbon in the reaction precursor complex directly forms the 2-substituted indole product. On the other hand, the benzene ring in the reaction complex undergoes 1,2-carbon migration on the C≡C triple bond to form the vinylidene complex. After cyclization and hydrogen transfer, the catalyst is regenerated to obtain 3-substituted indole product. The latter reaction process has relatively lower activation free energy and is also the main reaction channel for this reaction, which is consistent with published experimental results. This study provides a reasonable reaction mechanism and effective experimental supplement.