Scheme2.The conformational preferences of 3-fluoropiperidine (1)and 3,5-difluoropiperidine (2)a nd their TFA-(A), HCl-(B), and NH-(C)-analogues.T he free enthalpydifferences between the equatorial conformer to the axial conformer (DG)are presenteda sf ollows: DG Solvent( DG Gas Phase). The DG valuesfor TFA-, and for both HCl-, and NH-analoguesa re given in chloroform andwater,r espectively. All values are given in kcal mol À1 .Experimentally,a ll analogues of 1 and 2 showed high axialpreference. In NH-analogues 1C and 2C,wew ere unable to determine the orientation of the NÀHb ond becauseofafast H/D exchange in solution.[a] Both computationala nalysis and experimental observation were carriedo ut in toluene.