Facile Synthesis of Enantioenriched Cγ-Tetrasubstituted α-Amino Acid Derivatives via an Asymmetric Nucleophilic Addition/Protonation Cascade

An asymmetric nucleophilic addition/protonation reaction of 3-substituted oxindoles and ethyl 2-phthalimidoacrylate has been described. This strategy can give direct access to C-gamma-tetrasubstituted alpha-amino acid derivatives bearing 1,3-nonadjacent stereocenters with up to 98% yield, 94:6 dr, and > 99% ee. Dual activation is proposed in the transition state, and the opposite enantiomers can be obtained simply by changing cinchonidine-derived catalyst to the cinchonine analogue.