Single‐Operation Decarboxylative Mannich Reaction/Asymmetric Transfer Hydrogenation Cascade Process Directly Accesses 1,3‐Distereocentered β‐Sulfonamido Alcohols

Abstract

The 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.