Imidazolidine‐Pyrroloimidazolone Pyridine‐Ni(acac)<sub>2</sub> Complex Catalyzed Asymmetric Darzens Reaction of Isatins with Phenacyl Chlorides: A Chiral Amplification Effect
Han‐Le Wang, Tao Wei, Ru-Yun Bi, Ming‐Sheng Xie, Hai‐Ming Guo
Abstract
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 the catalyst, diverse spiro‐epoxyoxindoles with two new contiguous stereocenters were afforded in 82–99% yields, >20:1 dr, with 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.