Fine-Tuning Substrate-Catalyst Halogen-Halogen Interactions for Boosting Enantioselectivity in Halogen-Bonding Catalysis
A. C. Keuper, K. Fengler, F. Ostler, T. Danelzik, D. G. Piekarski, O. Garcia Mancheno
Angewandte Chemie Inetnational Edition, 2023
Abstract
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.