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 βketo 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.

Base mediated aza-[2 + 1] annulation and regioselective aziridine ring-opening cascade: mild synthesis of functionalized β-amino ketones from cyclic N-sulfonyl aldimines and α-carbonyl sulfonium salts

“…12 Additionally, sulfamate-derived cyclic aldimines are also useful building blocks for synthesizing β -Aks. 5,13 For example, Ma and co-workers described a novel Cu-catalyzed asymmetric decarboxylative Mannich reaction of sulfamate-derived cyclic aldimines with β -ketoacids to synthesize β -Aks (Scheme 1b). 5 a The group of Wang reported another asymmetric version of the Mannich reaction to achieve chiral β -Aks from cyclic aldimines using cinchona alkaloid as catalyst (Scheme 1c).…”