Imidazolidine‐Pyrroloimidazolone Pyridine‐Ni(acac)₂ Complex Catalyzed Asymmetric Darzens Reaction of Isatins with Phenacyl Chlorides: A Chiral Amplification Effect

Abstract

With phenacyl chlorides as simple nucleophilic species, the asymmetric Darzens reaction of isatins using Ni(acac)2 as the Lewis acid and imidazolidine‐pyrroloimidazolone pyridine as the ligand is reported. In the presence of 1 mol% of catalyst, diverse spiro‐epoxyoxindoles with two new contiguous stereocenters were afforded in 82‐99% yields, >20:1 dr, and 91‐99% ee. Chiral spiro‐epoxyoxindoles could undergo ring‐opening reactions in further transformations. The developed method was applied to the derivatization of complex molecules including indomethacin, gemfibrozil, and febuxostat‐derived α‐chloroketones. A strong positive nonlinear effect was observed, which was caused by the precipitation of a less‐soluble racemic catalyst complex.