Squaramide-Catalyzed Asymmetric Mannich Reactions of Azlactones with Isatin-Derived Ketimines: Access to α,β-Diamino Acid Derivatives Bearing Vicinal Quaternary Stereocenters
Zhanhuan Li, Jingyi Peng, Chonglong He, Jianfeng Xu, Hongjun Ren
Abstract
A highly stereoselective Mannich reaction of α-amino acid derived azlactones with isatin-derived ketimines enabled by a chiral bifunctional squaramide organocatalyst is reported, affording α,β-diamino acid derivatives bearing vicinal quaternary stereocenters in moderate to good yields (40-95%), moderate to excellent diastereoselectivities (3:1 → 20:1), and good to excellent enantioselectivities (66-97%). This reaction can be readily performed on gram scale, and the Mannich adduct could be easily converted to the corresponding α,β-diamino ester via simple operations.
Topics & Concepts
StereocenterChemistryIsatinSquaramideMannich reactionVicinalOrganocatalysisDiamino acidBifunctionalOrganic chemistryCatalysisAdductStereoselectivityEnantioselective synthesisCombinatorial chemistryBiochemistryPhylogenetic treeGene sequenceGeneAsymmetric Synthesis and CatalysisSynthesis and Catalytic ReactionsFluorine in Organic Chemistry