Squaramide-Catalyzed Three-Component Asymmetric [2 + 2 + 1] Cycloaddition Reaction Between 3-Hydroxy-1H-pyrrole-2,5-diones with Nitrosobenzene and Ethyl Diazoacetate

An asymmetric [2 + 2 + 1] cycloaddition reaction between three-component 3-hydroxy-1H-pyrrole-2,5-diones, ethyl diazoacetate, and nitrosobenzene was successfully developed. A new series of chiral polysubstituted chiral isoxazolidinopyrrolidinediones with three consecutive stereocentres were obtained in up to 87% yield with up to >20:1 dr and 78% ee. In addition, a scaled-up synthesis was carried out, and a possible reaction mechanism was also proposed.