Synthesis of Chiral <i>β</i>‐Trifluoromethyl‐<i>β</i>‐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.