Introducing the Chiral Constrained α-Trifluoromethylalanine in Aib Foldamers to Control, Quantify and Assign the Helical Screw-Sense**

Oligomers of alpha-aminoisobutyric acid (Aib) are achiral peptides that adopt 3(10) helical structures with equal population of left- and right-handed conformers. The screw-sense preference of the helical chain may be controlled by a single chiral residue located at one terminus. H-1 and F-19 NMR, X-ray crystallography and circular dichroism studies on new Aib oligomers show that the incorporation of a chiral quaternary alpha-trifluoromethylalanine at their N-terminus induces a reversal of the screw-sense preference of the 3(10)-helix compared to that of a non-fluorinated analogue having an l-alpha-methyl valine residue. This work demonstrates that, among the many particular properties of introducing a trifluoromethyl group into foldamers, its stereo-electronic properties are of major interest to control the helical screw sense. Its use as an easy-to-handle F-19 NMR probe to reliably determine both the magnitude of the screw-sense preference and its sign assignment is also of remarkable interest.