EXPERIMENTAL STUDIES OF THE ANOMERIC EFFECT .4. CONFORMATIONAL EQUILIBRIA DUE TO RING INVERSION IN TETRAHYDROPYRANS SUBSTITUTED AT POSITION-2 BY THE GROUPS ETHOXY, 2'-FLUOROETHOXY, 2',2'-DIFLUOROETHOXY, AND 2', 2', 2'-TRIFLUOROETHOXY

Equilibrium constants (K) for ring inversion equilibria in 2-(RO)-tetrahydropyrans (R=Et, CH2CH2,F, CH2CHF2 CH2CF3) have been determined from 13C nmr spectra recorded at 145-160K in CD2Cl2 and CFCl3/CDCl3 (85/15 by volume). Additional values of K were obtained at 250-270K from the acid-catalysed equilibration of is- and trans-2- (RO) -4-methyl tetrahydropyran (R as above). Plots of inK against T-1 gave values for ΔH° a→e of -0.26, -0.12, -0.05 and 0.13 kcal mol-1 for R=Et, CH2CH2F, CH2CHF2, and CH2CF3, respectively, in CD2Cl2. The corresponding values of ΔH° a→e for CFCl3/CDCl3, as solvent were -0.58, -0.15, -0.07 and 0.21 kcal mol-1, respectively. The derived ΔS° values were -2.33, -2.22, -2.25 and -2.24 cal K-1 mol-1, respectively, in CD2Cl2, and -4.65, -3.37, -3.30 and -3.03 cal K-1 mol-1, respectively, in CFCl3/CDCl3. The trends in ΔH° values are attributed to modifications of anti-periplanar n-o* stabilization (itself partly responsible for endo-and exo- anomeric effects) which occur as the number of electronegative fluorine substituents increases. For all substituents, axial conformations are the most abundant in the temperature range 120k-168. However, this finding is a consequence of the higher entropy of axial equatorial conformations; in at least two cases (R=Et and CH2CH2F) it is the equatorial conformation which has the lower enthalpy. The results confirm the importance of studying conformational equilibria over a wide range of temperature. © 1990.