Fine‐Tuning Substrate–Catalyst Halogen–Halogen Interactions for Boosting Enantioselectivity in Halogen‐Bonding Catalysis

A new approach towards highly enantioselective halogen‐bonding catalysis has been developed. To circumvent the intrinsic issues of the nature of the halogen‐bond (XB) and the resultant unresolved limitations in asymmetric catalysis, fine‐tuned halogen–halogen interactions between the substrate and XB‐donor were designed to preorganize the substrate in the catalyst's cavity and boost enantiocontrol. The present strategy exploits both the electron cloud (Lewis base site) and the sigma (σ)‐hole site of the halogen substituent of the substrates to form a tight catalyst–substrate–counteranion chiral complex, thus enabling a controlled induction of high levels of chirality transfer. Remarkable enantioselectivities of up to 95 : 5 e.r. (90 % ee) have been achieved in a model dearomatization reaction of halogen‐substituted (iso)quinolines with tetrakis‐iodotriazole multidentate anion‐binding catalysts. A new strategy towards boosted enantioselectivities in primary halogen‐bonding catalysis is presented. Fine‐tuned multiple halogen–halogen interactions between the substrate and halogen‐bond (XB)‐donor catalyst, through both the electron cloud (Lewis base site) and the sigma (σ)‐hole site of the incorporated halogen substituents, allows enantioselectivities of up to 90 % ee in model anion‐binding‐catalyzed dearomatization reactions.