Trifluoromethyl-modified dipeptides by ZrCl4-promoted aza-Henry reactions

Chiral (R)-1-phenylethylamine was successfully employed in a tandem aza-Henry addition–reduction reaction to give chiral β-nitro α-trifluoromethyl amines. A subsequent coupling reaction with N-Boc-protected amino acids leads to obtain optically pure CF₃-modified dipeptides carrying two different N-protecting groups. These peptidomimetic units are characterized by the presence of the CH(CF₃)NH] group as mimetic of the natural CONH] peptidic bond and can be used for the synthesis of more complex CF₃-modified peptides after selective deprotection of one of the two amine functions. 2D NMR spectral analyses were employed to determine the absolute configurations of all newly synthesized chiral compounds.