Conformational studies. XI. NMR studies of transannular substituent effects in cyclohexanols

3‐Fluoropiperidines and N‐Methyl‐3‐fluoropiperidinium Salts: The Persistence of Axial Fluorine

“…Substitution of cyclohexanol and its benzoate with electronegative groups at C-4 elicits eq/ax ratios from 49/51 to 26/74 at low temperatures. [28] Piperidine salts with RO, Br, and F at C-4 provide a similar spread for eq/ax conformers. [29,30] Dimethylpiperidinium ions with OH and OAc at C-3 were reported to give eq/ax ratios of 49/52 and 34/66, respectively, in perdeuteromethanol.…”

“…[29,30] Dimethylpiperidinium ions with OH and OAc at C-3 were reported to give eq/ax ratios of 49/52 and 34/66, respectively, in perdeuteromethanol. [28] These ratios correspond to a relative stabilization of the axial conformer by 0.1-0.8 kcal mol À1 . Even more striking is the position of the acid-catalyzed chemical equilibrium in substituted dioxolanes 28 reported in a series of publications by the Eliel group.…”

“…Finally, while the conformational analysis of any number of substituted cyclohexanes and piperidines yields a mixture of rapidly equilibrating conformers, [1,27,28,29] the 3-fluoropiperidine salts are satisfyingly "clean". Yet the energy difference is certainly no more than 2-3 kcal mol…”

NMR spectroscopic conformational analysis of 4‐methylene‐cyclohexyl pivalate—The effect of sp2 hybridization

“…[4] There is one earlier manuscript dealing with 1,4transannular effects in 4-substituted cyclohexanol on the present conformational equilibrium (determined by line width measurements of the R 2 C(OH)H proton signal in nuclear magnetic resonance (NMR) spectra at room temperature); [5] the axial conformation of the OH substituent increases with the electron attracting ability of C-4 substitution. [5] Steric destabilization of the axial conformer with increasing 1,3-diaxial interactions has been observed in various aliphatic cyclohexyl esters (−O−COAlk), [6] and the effect of hyperconjugation in 1,4-disubstituted cyclohexanes due to the polar effect of the second −OR substituent in 4position proved to be 0.5-0.7 kcal/mol (−OR= −OMe, −OEt, −Oiso-Pr, −Otert-Bu) [6] and 0.3-0.5kcal/mol (−OR =−OCOMe, −OCOEt, −OCOiso-Pr, −OCOtert-Bu), [3] respectively, preferring by this energy amount the axial conformation of the −OR substituent at cyclohexyl. Finally, the carbonyl group in position 4 too increases the axial orientation of the corresponding −OR substituents; [1] quantitative information by low-temperature dynamic NMR spectroscopy, however, is hardly available because the barrier to ring interconversion proved to be too low to be studied in solution.…”

“…To better understand structural changes, the conformational equilibria of 1, 2 and 4 were computed on the density functional theory (DFT) level of theory (CDCl 3 as the solvent). 5 The computational results are given in Table 1, the conformational equilibrium of the exo-methylene ester 1 is visualized in Figure 3 (GS ⇌ TS ⇌ GS); the corresponding transition states of 2 and 4 are given in Figure 4.…”