Large-Scale Asymmetric Synthesis of Fmoc-()-2-Amino-6,6,6-Trifluorohexanoic Acid.

Here we report the first large-scale synthesis of Fmoc-()-2-amino-6,6,6-trifluorohexanoic acid via asymmetric alkylation of chiral Ni(II)-complex of glycine Schiff base with CF(CH)I. The synthesis was performed on over 100 g scale and can be recommended as the most advanced procedure for reliable preparation of large amounts of enantiomerically pure Fmoc-()-2-amino-6,6,6-trifluorohexanoic acid for protein engineering and drug design. Chiral auxiliary used in this protocol can be >90 % recovered and reused.