Synthesis of Chiral β-Trifluoromethyl-β-Amino Acid Derivatives in Aqueous Medium

Abstract

A practical synthesis of chiral β-trifluoromethyl-β-amino acids is reported by using water as a reaction medium to facilitate the diastereoselective aza-Michael addition of aromatic amines to chiral β-trifluoromethyl-α,β-unsaturated oxazolidinone. A variety of aromatic amines could serve as a suitable nucleophile that readily undergo nucleophilic conjugate addition at ambient temperature to provide the corresponding β-trifluoromethyl-β-amino acid derivatives in excellent combined yields (up to 97 %) with moderate to good diastereoselectivities (up to 3 : 1). Being complementary to the precedent methods, this work offers the advantages, e. g., a green and environmentally friendly reaction medium, a stable and readily synthesized chiral starting material, and a simple and practical operation providing enantioenriched β-trifluoromethyl-β-amino acids which are found major applications in advanced organic synthesis and medicinal research field.