Stereolabile and Configurationally Stable Atropisomers of Hindered Aryl Carbinols

Carbinols of the Ar−C(OH)R2 type, Ar being o-isopropylphenyl, exist as stereolabile syn-clinal (sc)
and anti-periplanar (ap) atropisomers when R = Me, Et, i-Pr. In the latter compound, the major
atropisomer also comprises two enantiomeric forms that interchange with a barrier of 6.4 kcal
mol-1. X-ray diffraction, NOE experiments, and ab initio calculations indicate that the sc-atropisomer
is the more stable form when R = Me, i-Pr, t-Bu but is the less stable one when R = Et. NMR
spectra at variable temperature allowed the determination of the barriers for the interconversion
of the sc- into the ap-atropisomers (ΔG⧧ = 7.6, 8.8, and 13.5 kcal mol-1 for Me, Et, i-Pr, respectively).
When R is a tert-butyl group, the two atropisomers are configurationally stable:  the ap-atropisomer
is obtained as the kinetic controlled compound, which can be transformed into the thermodynamically more stable sc-atropisomer with a free energy of activation of 29.3 kcal mol-1. Both
atropisomers exhibit restricted rotation of the tert-butyl moiety, the corresponding ΔG⧧ values being
9.4 and 8.8 kcal mol-1 for the sc- and ap-atropisomer, respectively.