The first 4,4′-imidazolium-tagged C₂-symmetric bis(oxazolines): Application in the asymmetric Henry reaction

Highly efficient and recyclable imidazolium-tagged bis(oxazolines), with an imidazolium tagged onto the 4,4′-position of the box, have been designed and prepared for the first time. They have been synthesized from dimethylmalonic acid and used as chiral ligands in the copper(II)-catalyzed classic asymmetric Henry reaction between aldehydes and nitromethane. A systematic analysis of the anions showed that the best ligand was one of a medium size; the catalyst achieved a high activity and enantioselectivity as well as good recyclability, i.e., product (R)-11k was attained at 94% ee in MeOH. Moreover, the catalyst was successfully recycled six times, without an obvious loss in activity or enantioselectivity. Finally, a theoretical mechanistic study was conducted to explain the origin of the enantioselectivity and how the size of anions affects the reaction.