Conjugated additions of amines and β-amino alcohols to trifluorocrotonic acid derivatives: synthesis of ψ[NHCH(CF3)]-retro-thiorphan

The aza-Michael addition of amines and β-amino-alcohols to trifluorocrotonic acid derivatives is described. The reactions occurred in good to excellent yields, but low stereocontrol. The title reaction has been used as a key step for the synthesis of trifluoroethylamine mimics of retro-thiorphan, which showed low inhibitory activity of NEP (constant inhibition at the molar level).