Tandem Synthesis Of β-hydroxysulfonamide And β-carbonylsulfonamide By Decarboxylation Mannich/asymmetric Hydrogen Transfer And CN Bond Cleavage

In recent years,stereocentric sulfonamides are important motifs of many drugs and bioactive compounds,which carbonyl sulfonamides exist in a variety of active natural products,cyclic hydroxysulfonamides and amine phosphonates have many uses in antidepressants,so the preparation of chiral sulfonamides has attracted much attention.Besides,chiral hydroxysulfonamides are important scaffolds for bradykinin B1 receptor antagonists and potassium channel blockers.Therefore,the synthesis of hydroxysulfonamides and their derivatives has great potential application value.The development of one-pot tandem reactions has 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.In order to solve these problems,an integrated Cu/bisoxazoline and Ru/diamine co-catalyst system was proposed to achieve efficient decarboxylative Mannich/asymmetric transfer hydrogenation enantioselective cascade reaction for the direct preparation of 1,3-distereocentered β-hydroxysulfonamides.The cascade process started with Cu/bisoxazoline catalyzed decarboxylation Mannich reaction of sulfonimide and β-ketoacid to obtain chiral β-carbonylsulfonamide,then achieved asymmetric transfer hydrogenation in one-pot without separation and purification,a wide range of chiral β-hydroxysulfonamides with80-95% yield,86-99% ee,64:36-99:1 dr were produced.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.Because of the high bond energy,the C-N single bonds is very tight and difficult to cleavage.In this study,we found that Rh catalyst promot the C-N bonds cleavage of carbonyl sulfonamides.By optimizing the conditions,the C-N bonds of sulfonamides was cleavaged and a series of ketones were prepared with high yields(75-90%).This method can well realize the cleavage of C-N bonds in carbonyl sulfonamides,overcome the difficulties in conventional reports,and has high reference value for subsequent research.