Stereodivergent Construction of Spiropyrrolidine‐ <i>γ</i> ‐Butyrolactones Enabled by Cu/Ru Sequential Catalysis and Stereoselective Reduction

The stereodivergent synthesis of spiroheterocycles bearing multiple stereocenters is a pivotal yet challenging frontier in asymmetric catalysis, particularly for rigid scaffolds integrating pharmacophoric pyrrolidine and γ-butyrolactone motifs with structural complexity and saturation. While the strategy of synergistic dual catalysis has advanced the stereodivergent construction of vicinal stereocenters, the precise control of 1,3-nonadjacent stereocenters in spirocyclic architectures remains underdeveloped. Herein, we report a bimetallic Cu/Ru sequential catalytic platform enabling stereodivergent access to spiropyrrolidine-γ-butyrolactones with three skipped stereocenters. By orchestrally integrating Cu-catalyzed asymmetric alkylation with Ru-mediated tandem asymmetric transfer hydrogenation/lactonization, this one-pot protocol achieves independent stereochemical control over two successively formed 1,3-stereocenters through sequential catalytic cycles. A stereoselective imine reduction further installs the third stereocenter with exceptional diastereoselectivity, completing the three-dimensional chiral architectures that were otherwise inaccessible. Control experiments validate the sequential catalytic pathway and reveal the essential role of Cs₂CO₃ in facilitating lactonization.