Base-controlled diastereoselective [3+2]-cycloaddition and Michael addition of isatin ketonitrones and chalcones to construct spiropyrrolidine oxoindoles and γ-substituted isatin ketonitrones

Abstract

The synthesis of novel spiropyrrolidine oxoindole/γ-substituted isatin ketonitrone derivatives was reported, using [3+2]-cycloaddition/Michael addition of isatin ketonitrone 1,3-dipoles, generated from the condensation of isatins and arylhydroxylamines, with chalcones under base-controlled conditions. The spiropyrrolidine oxoindoles bearing four contiguous stereocenters, including a spiroquaternary stereocenter fused in one ring structure, were smoothly acquired in low to high yields (18–98%) with excellent diastereoselectivities (>20 : 1 dr) using t-BuOK as a catalyst. Meanwhile, the dominant products, γ-substituted isatin ketonitrones, were obtained with low to excellent diastereoselectivities (1 : 1 – >20 : 1 dr) using DBU instead of t-BuONa. The synthesized compounds (>60 examples) were well characterized through different spectroscopic techniques, such as single crystal XRD, FTIR, NMR, and mass spectral analysis.