Cross-assembly confined bifunctional catalysis via non-covalent interactions for asymmetric halogenation

Bifunctional catalysis plays a key role in the synthesis of useful compounds. By offering a sterically confined environment, chiral bifunctional catalysts can achieve highly enantioselective reactions. However, introducing suitable substituents to create a confined microenvironment for asymmetric catalysis on many occasions involves tedious procedures, leading to inefficient reaction optimi-zation. Herein, we report a proof-of-concept study on formulating confined bifunctional catalysts by linking catalytic species via non -covalent interactions (NCIs). Chiral phosphate and achiral cyclopro-penium cations cross-assembled to give a confined bifunctional system for asymmetric bromo-semipinacol rearrangement. By changing the achiral catalyst to aminopyridine, the system can be applied to asymmetric bromocycloetherification. These reactions are largely optimized by simply changing the achiral catalyst. A computational study revealed that the strength of the NCI donor is crucial in creating tighter catalytic pockets to amplify the effect of enantiofacial discrimination of substrates.