Expedient Asymmetric Synthesis of (S)-2-Amino-4,4,4-trifluorobutanoic Acid via Alkylation of Chiral Nucleophilic Glycine Equivalent

Abstract

Here we disclose a practical asymmetric synthesis of an enantiomerically 97.8% ee pure N-Fmoc derivative of (S)-2-amino-4,4,4-trifluorobutanoic acid performed on >10 g scale of the target product. The method is based on alkylation (CF3–CH2–I) of a new generation of a chiral nucleophilic equivalent conducted at ambient temperature with an excellent stereochemical outcome. The developed protocol does not require any chromatographic separations and includes only one purification step via recrystallization of the final product.