Highly Enantioselective Organocatalysis with Bidentate Halogen Bond Donors

As the employment of "non-classical" non-covalent interactions like halogen bonding (XB) in asymmetric catalysis is still at a very early stage, there are significant challenges to overcome. In some reported cases, the relevance of halogen bonding to the catalytic action is unclear, while in others, catalyst activity is limited. Herein, we present the second generation of a bidentate iodine(I)-based halogen bond donor as a modifiable and highly active chiral halogen bonding catalyst. With these modified derivatives, high stereocontrol of up to 98% ee could be achieved in a model Mukaiyama aldol reaction for a range of different substrates. Importantly, the crucial role of halogen bonding in this catalytic process was demonstrated by the low performance of the non-iodinated variants and by DFT calculations. The latter also indicate that the stereoinduction is based on the imposed orientation of the substrates towards each other.