The CF bond as a tool in the conformational control of amides

Solid state and theoretical evaluation of β-fluoroethyl esters indicate a fluorine-ester gauche effect

“…This contra intuitive preference appears to originate from vicinal interactions possible between the polar C-F bond and other polar covalent bonds. In a related example, we recently demonstrated a fluorineamide gauche effect [6,7] in which the C-F bond is vicinal to the C-N(CO) bond of an N-b-fluoroethylamide 2 as shown in Fig. 1.…”

“…The largest difference in the residual map is À0.224 e.Å À3 . The Flack parameter refined to 0.2 (7). Crystallographic data have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication 212515.…”

“…1) can be compared to 2-fluoroethanol 3 and that of N-b-fluoroethylamide 2, which displays a strong gauche preference [6,7]. It has already been shown that such esters adopt a gauche preference in solution.…”

Conformational impact of pentafluorosulfanylation on acyclic aliphatic molecules

“…Individual fluorine atoms influence conformation primarily through electrostatic or dipolar interactions [1,2]. Hydrogen bonding interactions are however frequently of less importance in organofluorine compounds [3][4][5] where fluorine is a poor hydrogen bond acceptor as consequence of the high electronegativity and lower polarizability of fluorine.…”

NMR‐Solution Structures of Fluoro‐Substituted β‐Peptides: A 314‐Helix and a Hairpin Turn. The First Case of a 90° OCCF Dihedral Angle in an α‐Fluoro‐Amide Group

“…The first reported structure of this type dates back to 1962 [8], with recent systematic investigations having been published by O Hagan and co-workers [7] [9]. For other a-fluoro carbonyl compounds, such as N,N-dialkyl-a-fluoro amides, a-fluoro esters, or a-fluoro ketones, synclinal (sc, < 908, gauche), anticlinal (ac, > 908, < 1808), and syncoplanar (sp, AE 08) dihedral FÀCÀC¼O angles have also been reported [10 -12] There is, so far, no qualitative model that would rationalize the pronounced stability of the ap-conformation of a-fluoro amides of the type shown in Fig.…”