Bidentate Chiral Bis(imidazolium)-Based Halogen Bond Donors: Synthesis and First Applications in Enantioselective Recognition and Catalysis

Even though halogen bonding – the noncovalent interaction between electrophilic halogen substituents and Lewis bases – has now been established in molecular recognition and catalysis, its use in enantioselective processes is still very little explored. Herein, we present the synthesis of chiral bidentate halogen bond donors based on two iodoimidazolium units with rigidly attached chiral sidearms. With these Lewis acids, chiral recognition of a racemic diamine is achieved in NMR studies. DFT calculations support a 1:1 interaction of the halogen bond donor with both enantiomers and indicate that the chiral recognition is based on a different spatial orientation of the Lewis bases in the halogen bonded complexes. In addition, moderate enantioselectivity is achieved in a Mukaiyama aldol reaction with a preorganized variant of the chiral halogen bond donor. This represents the first case in which asymmetric induction was realized with a pure halogen bond donor lacking any additionally active functional groups.