Halogen‐Bond‐Assisted Anti ‐Selective Henry Reaction Promoted by a Chiral Nickel Catalyst

A novel catalytic asymmetric anti ‐selective Henry reaction was designed by making an extended conformation (like a pseudo ‐diequatorial orientation) of the R‐substituent of aldehydes and the R′‐substituent of nitronates. The o ‐X‐F 4 ‐PyBidine‐Ni(OTf) 2 (X = Br, I) gave the anti ‐nitroaldol products with up to 96:4 dr and 99% ee. DFT calculations of the transition state suggest that the halogen‐bonding interaction of the o ‐X‐F 4 ‐PyBidine ligand with the π‐electron of the aromatic aldehyde assists the highly anti ‐selective asymmetric Henry reaction in the cooperative nickel‐catalyzed reaction. The current study demonstrates that the soft molecular halogen bond made by the σ–hole–π–electron interaction effectively promotes catalysis in a protic solvent.