Royal Society of Chemistry, New Journal of Chemistry, 12(39), p. 9504-9517
DOI: 10.1039/c5nj01434d
Full text: Download
Due to the importance of axially chiral biaryl derivatives as chiral auxiliaries and/or ligands for asymmetric synthesis as well as their structural role in bioactive natural products, continuous efforts have been undertaken to propose efficient methods for their atropo-selective synthesis. As a consequence, proposing robust and reliable analytical tools able to discriminate the signal of atropisomeric enantiomers becomes crucial to evaluate the enantiomeric excesses of mixtures. In this work, we show how several multi-nuclear 1D/2D-NMR techniques using homopolypeptide chiral liquid crystals as aligning solvents can provide a panel of analytical possibilities (through differences of chemical shift anisotropies, dipolar and quadrupolar residual couplings) to spectrally discriminate enantiomers of a large collection of trisubstituted axially chiral biphenyls. Approaches involving 31P, 13C and 2H 1D- or 2D-NMR experiments at natural abundance level are explored. Among noteworthy results, the first examples of spectral enantioseparations using 31P nuclei as nuclear probe are reported. Finally, the role of electronic factors and shape anisotropy that affects the efficiency of chiral discrimination mechanisms are examined and discussed. Molecular modeling calculations were carried out to establish the electronic profile of these analytes in order to understand and rationalize the 13C-{1H} NMR results.