Experimental and theoretical data indicate that, for alpha-fluoroamides, the FCC(O)N(H) moiety adopts an antiperiplanar conformation. In addition, a gauche conformation is favoured between the vicinal CF and CN(CO) bonds in N-beta-fluoroethylamides. This study details the synthesis of a series of fluorinated beta-peptides (1-8) designed to use these stereoelectronic effects to control the conformation of beta-peptide bonds. X-ray crystal structures of these compounds revealed the expected conformations: with fluorine beta to a nitrogen adopting a gauche conformation, and fluorine alpha to a CO group adopting an antiperiplanar conformation. Thus, the strategic placement of fluorine can control the conformation of a beta-peptide bond, with the possibility of directing the secondary structures of beta-peptides.
Peddie, V., Butcher, R. J., Robinson, W. T., Wilce, M. C., Traore, D. A. K., & Abell, A. D. (2012). Synthesis and conformation of fluorinated beta-peptidic compounds. Chemistry - A European Journal, 18(21), 6655 - 6662. https://doi.org/10.1002/chem.201200313