Conformational and stereoelectronic investigation in 1,2-difluoropropane: The gauche effect

Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design

“…The conformational preferences of vicinal fluoroalkanes provides another interesting opportunity to exploit the effects of replacing H by F, taking advantage of the preference for fluorines on adjacent carbons to adopt a gauche relationship. This approach to conformational bias is based on stabilization by a combination of favorable dipole−dipole, electrostatic, steric, and hyperconjugative interactions (Table ). ,,− …”

Conformational Analysis of 1-Chloro- and 1-Bromo-2-propanol

“…1,2-Difluoroethane − and 1,2-difluoropropane experiences the gauche effect, i.e., the abnormal preference of gauche vicinal fluorine atoms instead of the less sterically/electrostatically hindered anti conformation in an ethane fragment. Replacement of a fluorine atom by the hydroxyl group to give 2-fluoroethanol maintains the gauche preference, which was found due to not being caused by an intramolecular hydrogen bond since the n F → σ* OH interaction was not detected by natural bond orbital (NBO) analysis .…”

On the stereoelectronic effects governing the rotational isomerism of 1,2-di-haloethanes

“…The rotational isomerism of compounds containing the 1,2-difluoroethane fragment has been extensively studied and the synclinal preference often attributed to the gauche effect, the tendency of keeping close certain substituents [1][2][3][4][5]. The origin of this effect for such compounds is assumed to be due to antiperiplanar CAH/ CAF* hyperconjugation, though other recent interpretations have been applied to different systems having vicinal electronegative substituents [6,7].…”