Iodine(i)-based and iodine(iii)-based halogen bond catalysis on the Friedel-Crafts reaction: a theoretical study

Halogen bond catalysis, especially iodine derivatives catalysis, has attracted increasing attention in recent years owing to the advantages of relatively cheap, stable, green, easy to handle, and favorable catalytic activity. To obtain insights into the catalytic mechanism and activity of halogen bond donor catalysts, iodine(i)-based and iodine(iii)-based halogen bond catalysis on the Friedel-Crafts reaction were investigated in this study. The entire reaction contains several key steps: carbon-carbon bond coupling, proton transfer, hydroxyl departure, indole addition, and deprotonation process. According to the energetic span model, iodine(iii)-based donor catalysts exhibit higher catalytic activity than iodine(i)-based catalysts and double cationic catalysts are more potent than single cationic ones. For halogen bond catalysis, the Gibbs energy barriers have linear relation to the electron density at the halogen bond critical points. Furthermore, the Gibbs energy barriers are also linearly related to the integral charge values of the increased region of electron density outside the oxygen atom of reactants. Therefore, the stronger halogen bond results in lower Gibbs energy barrier, and the stronger polarization further benefits the halogen bond catalysis.