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

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 beta-sulfonamido alcohols. Through this cascade process, an initial Cu/bisoxazoline-catalyzed decarboxylative Mannich reaction of a cyclic aldimine and a beta-keto acid to afford a chiral beta-sulfonamido ketone, followed by asymmetric transfer hydrogenation of this in situ generated ketone, produces a wide range of chiral beta-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.

Automated summary

The development of cooperative catalysis is important for multi-step sequential enantioselective organic transformations. This study presents the design of an integrated Cu/bisoxazoline and Ru/diamine co-catalyst system for the direct preparation of 1,3-distereocentered beta-sulfonamido alcohols. The cascade reaction enables efficient and selective synthesis of chiral products.