Structure, Conformation, Stereodynamics, Dimer Formation, and Absolute Configuration of Axially Chiral Atropisomers of Hindered Biphenyl Carbinols

NMR spectra of biphenyl derivatives bearing a single CR2OH substituent in the ortho position indicate
that they exist as sp (more stable) and ap (less stable) conformers, due to the restricted rotation about the
Ar−CR2OH bond. When R = Et (compound 2) the corresponding rotation barrier was determined (7.5
kcal mol-1) by line shape simulation of the low-temperature NMR spectra. Introduction of the prochiral
i-Pr group in the position 3‘ of a biphenyl with the CMe2OH substituent in the position 2 (4) allowed the
determination of the enantiomerization barrier (due to the Ar−Ar bond rotation) for the stereolabile
axially chiral atropisomers (13.95 kcal mol-1). DFT computations of these barriers were all in agreement
with the experiments. Biphenyls bearing two CR2OH groups in the 2,2‘ positions were found to exist as
configurationally stable atropisomers:  when R = Me (7) they were separated by enantioselective HPLC
and the absolute configuration assigned on the basis of the corresponding CD spectra. In solution,
compounds 6 (R = H) and 7 (R = Me) were found to originate a dimer, due to H-bond interactions
between two enantiomers. In the case of 7, the free energy of activation (9.5 kcal mol-1) for the exchange
of the monomer with the dimer could be measured, for the first time, by dynamic NMR. The conformational
preferences, predicted by computations for the biphenyls with two CR2OH substituents in the 2,2‘ positions,
were confirmed by X-ray diffraction in the case of R = H (6), R = Me (7), and R = i-Pr (9).