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

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.