Computational Design of Bidentate HypervalentIodine Catalysts in Halogen Bond‐MediatedOrganocatalysis

In recent years, halogen bond‐based organocatalysis has garnered significant attention as an alternative to hydrogen‐based catalysis, capturing considerable interest within the scientific community. This transition has witnessed the evolution of catalytic scaffolds from monodentate to bidentate architectures, and from monovalent to hypervalent species. In this DFT‐based study, we explored a bidentate hypervalent iodine(III)‐based system that has already undergone experimental validation. Additionally, we explore various functionalisations (‐CF$_3$, ‐CH$_3$, ‐tBu, ‐OH, ‐OMe, ‐NO$_2$, ‐CN) and scaffold modifications, such as sulfur oxidation, theoretically proposed for an indole‐based Michael addition. The investigated systems favour bidentate O‐type binding, underlining the importance of ligand coordination in catalytic activity. Electron‐deficient scaffolds exhibited stronger binding and lower activation energies, indicating the pivotal role of electronic properties for $\sigma$‐hole‐based catalysis. Of these groups, Lewis‐base‐like moieties formed stabilising intramolecular interactions with hypervalent iodines when in the ortho‐position. Furthermore, inductive electron withdrawal was deemed more effective than mesomeric withdrawal in enhancing catalytic efficacy for these systems. Lastly, increasing sulfur oxidation was theoretically proven to improve catalytic activity significantly.