Is the metal involved or not? A computational study of Cu(I)-catalyzed [4+1] annulation of vinyl indole and carbene precursor

The Cu(I)-catalyzed [4 + 1] annulation of vinyl indoles and a carbene precursor is a powerful method for constructing cyclopentaindole derivatives. Density functional theory (DFT) calculations were used to elucidate the mechanism and regioselectivity of this reaction. After Cu-assisted indole C3-alkylation, direct 1,5-annulation was favored over the Cu-assisted annulation pathway. Furthermore, the regioselectivity for 1,5-annulation was attributed to the generated five-membered-ring product being more stable than the three-membered-ring product from 1,3-annulation, which was the kinetically favored pathway. (C) 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

In this study, the mechanism and regioselectivity of the Cu(I)-catalyzed [4 + 1] annulation of vinyl indoles and a carbene precursor were investigated using density functional theory (DFT) calculations. The results showed that direct 1,5-annulation was favored over the Cu-assisted annulation pathway, and the regioselectivity for 1,5-annulation was attributed to the greater stability of the generated five-membered-ring product compared to the three-membered-ring product from 1,3-annulation, which was kinetically favored.