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

Abstract 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 Cs 2 CO 3 in facilitating lactonization.