Enantioselective synthesis of β-aryl-γ-amino acid derivatives via Cu-catalyzed asymmetric 1,4-reductions of γ-phthalimido-substituted α,β-unsaturated carboxylic acid esters

A series of chiral beta-aryl-substituted) gamma-amino butyric acid derivatives were synthesized in good enantioselectivities via the Cu-catalyzed asymmetric conjugate reduction of gamma-phthalimido-alpha,beta-unsaturated carboxylic acid esters using Cu(OAC)(2)center dot H(2)O as a catalyst precursor, (S)-BINAP as a ligand, PMHS as a hydride source, and t-BuOH as an additive. The methodology has been applied successfully to the enantioselective synthesis of a chiral pharmaceutical, (R)-baclofen.