Organocatalytic Acetalization of Aldehydes Utilizing N‐Heterocyclic Iod(az)olium Salts as the Halogen‐Bonding Catalysts

ABSTRACT The formation of acetals from aldehydes is a valuable transformation in organic synthesis and biological systems. In this study, complementing experimental screening and density functional theory (DFT) calculations were performed to predict the relative effectiveness of five potential halogen‐bonding (XB) catalysts for the acetalization reaction between 3‐phenylpropanal and methanol. By analyzing electrostatic potential maps, I⋯O distances, binding energies, and Gibbs free energy changes, the computational study provided a theoretical ranking to guide and rationalize catalyst selection, highlighting the synergy between experimental and computational approaches in catalyst development. We report a mild, cost‐effective, and organocatalytic protocol employing iod(az)olium salts as XB catalysts to promote the acetalization of various aliphatic and aromatic aldehydes, achieving good yields.