A synthetic and NMR study of some highly substituted cyclohexanols and derivatives

Abstract

A series of cis- and trans-3-(aryl)-3,5,5-trimethylcyclohexanols and their acetyl and benzoyl derivatives have been prepared and investigated through detailed N M R studies. These studies included an extensive characterization of stereochemistry by use of the lanthanide shift reagent (LSR) europium(III) tris-6,6,7,7,8,8,8- heptafluoro-2 ,2-dimethyl- 3,5-octadione, Eu(FOD)₃. From the interaction of these alcohols and ester derivatives with the LSR, a set of association constants and bound chemical shifts have been calculated for the two coupled equilibria indicated. Regression analysis of the concentration dependence of the lanthanide-induced shifts (LIS) of the substrate provides accurate proton chemical shifts ([?]-values) in the absence of the LSR. The results of these NMR studies are consistent with the presence of a biased, mobile equilibrium between two chair-like conformers. For the trans-3-(aryl)-3,5, 5-trimethylcyclohexyl systems, the preferred conformation is that where the C-3 aromatic moiety is axial, while for the cis-isomers, the aromatic substituent prefers to be equatorial. For these compounds, a somewhat flattened chair form of the cyclohexyl ring apparently exists, caused by syn-axial compression between the two substituents at C-3 and C-5. These L S R studies also yield an estimate of the conformational biasing of the ester moiety, where it was found that the preferred conformation is that w h e r e the C-l axial proton of the cyclohexyl ring and the carbonyl group of the ester are eclipsed. The LIS studies also provide numerous examples of upfield europium-induced shifts, as well as "back-bending" of some of the LIS curves found in the case of the cis-acetates and benzoates.