AbstractThe development of cooperative catalysis is of great significance for multi‐step sequential enantioselective organic transformations. However, the complicated subtle environments and inherent mutual deactivations of chiral dual catalysts pose a great challenge in a single operation. To address these issues, we here report the rational design of an integrated Cu/bisoxazoline and Ru/diamine co‐catalyst system, which enables a decarboxylative Mannich reaction/asymmetric transfer hydrogenation enantioselective cascade reaction for the direct preparation of 1,3‐distereocentered β‐sulfonamido alcohols. Through this cascade process, an initial Cu/bisoxazoline‐catalyzed decarboxylative Mannich reaction of a cyclic aldimine and a β‐keto acid to afford a chiral β‐sulfonamido ketone, followed by asymmetric transfer hydrogenation of this in situ generated ketone, produces a wide range of chiral β‐sulfonamido alcohols in 80–95% yields with 86–99% ee and 64:36–99:1 dr. Advantageous feature of this co‐catalyst system lies in the cooperative catalytic process, which greatly enhances the catalytic efficiency compared with the single‐step reactions, making it attractive for gaining direct access to the diastereoselective 1,3‐distereocenter.magnified image