Studies On Cu-Catalyzed Asymmetric Decarboxylative Mannich Reaction Of β-Ketoacids With Cyclic Aldimines

The controlled excision of carbon dioxide from organic molecules, commonlyknown as decarboxylation, is a valuable transformation that is fundamental tobiochemistry and broadly utilized in synthetic molecule construction. What’s more,the decarboxylative Mannich reaction reprents a powerful tool for the synthesis ofnatural products and biologically active compounds.In this thesis, asymmetric decarboxylative Mannich reaction of β-ketoacids withcyclic aldimines has been developed in the presence of the copper complexes of chiralbisoxazoline ligands. A series of chiral β-aminoketos were obtained with excellentyields (90–99%) and enantioselectivities (92–99%ee). The catalyst loading could bereduced to0.1mol%to give good results. Notably, the decarboxylative Mannichproduct can be applied to the synthesis of chiral chroman-4-amine in several steps,which was the core scaffold of several drug candidates such as Bradykinin B1receptor antagonist. Furthermore, HRMS experiments have been performed toelucidate that nucleophilic addition of β-ketoacid to the cyclic aldimines occur prior tothe decarboxylation of the β-ketoacid during this decarboxylative Mannich process.