Enantioselective organocatalytic amination of 2-perfluoroalkyl-oxazol-5(2H)-ones towards the synthesis of chiral N,O-aminals with perfluoroalkyl and amino groups

Abstract

Herein, the first highly enantioselective amination at the C-2 position of 2-perfluoroalkyl-oxazol-5(2H)-ones to phenylazocarboxylates using a (1R,2R)-cyclohexane-1,2-diamine-derived urea–tertiary amine as a bifunctional catalyst is presented. Two efficient asymmetric transformation processes were achieved through the formation of the intermediate 2-(perfluoroalkyl)-oxazol-5(2H)-ones starting from simple amino acids or via the formation of the intermediate phenylazocarboxylates starting from N-acyl arylhydrazines. Both processes resulted in chiral N,O-aminal derivatives with a quaternary center in good yields (up to 91%) with excellent enantioselectivities (up to 99%). These efficient atom-economical strategies lead to the highly enantioselective construction of N,O-acetal derivatives containing perfluoroalkyl and amino moieties.