N-Heterocyclic-Carbene (NHC)-catalyzed reactions of α-bromo α,β-unsaturated aldehydes for one-pot cascade stereoselective synthesis of Spirooxindole γ-butyrolactones​

Journal of Molecular Chemistry

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Spirooxindole frameworks, especially γ-butyrolactones, are privileged scaffolds in medicinal chemistry due to their structural rigidity and broad biological relevance. However, their stereoselective synthesis remains a challenge with existing methods often requiring toxic metals or harsh conditions. Herein, we report a novel practical, metal-free, and stereoselective N-heterocyclic carbene (NHC)-catalyzed cascade [3+2] annulation of 3-hydroxyoxindoles with α-bromo-α,β-unsaturated aldehydes to stereoselective delivered spirooxindole γ-butyrolactones in high yields (67–95%) with excellent diastereoselectivity (>20:1 dr) under mild reaction conditions. This method demonstrates broad substrate tolerance, accommodating diverse N1-substituted 1,2-binucleophiles 3-hydroxyoxindoles and electron-rich 1,3-bielectophiles α-bromoenals. Eco-friendly, sustainable transformation expands the synthetic toolbox for spirooxindole γ-butyrolactones, offering a valuable entry to biologically relevant scaffolds.