Chiral Triazole-substituted Iodonium Salts in Enantioselective Halogen Bond Catalysis

Herein, we present the synthesis of chiral triazole-based diaryliodonium salts and their application as monodentate asymmetric iodine(III) derivates in halogen bond (XB) catalyzed reactions. These potential Lewis acids were successfully benchmarked in the vinylogous Mannich reaction of cyanomethyl coumarin with isatin-derived ketimine to obtain the addition product in up to 99% yield and >99:1 e.r. Furthermore, these halogen bond catalysts allowed an efficient functionalization of ketimines with various alcohols toward N,O-acetals in up to 99% yield and 90:10 e.r. Additionally, we studied the origin of the enantioselectivity based on Density Functional Theory (DFT) and the catalyst crystal structure. These unveiled the first approach of asymmetric induction facilitated by using σ-hole stabilized chiral moieties in iodine(III)-based catalysts and exclusively predicated upon XB activation.