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-F4-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-F4-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.