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 an approach of
asymmetric induction facilitated by using σ-hole stabilized
chiral moieties in iodine(III)-based catalysts, predominantly predicated
upon XB activation.