Stereocontrolled Synthesis of ψ[CH(CF3)NH]Gly-Peptides

[reaction: see text] A novel class of peptidomimetics having a stereogenic [CH(CF(3))NH] replacement for a [CONH] peptide bond has been synthesized. The new compounds have been obtained in a stereocontrolled fashion using a kinetically controlled aza-Michael addition of chiral alpha-amino acid esters to trans-3,3,3-trifluoro-1-nitropropene. The stereoselectivity is strongly influenced by the solvent, the base, its stoichiometry, and the R side-chain. Diastereomeric ratios higher than 11:1 were achieved using H-Val-OtBu.HCl in toluene with 1.1 equiv of DIPEA.