Enantiotopic discrimination in the NMR spectrum of prochiral solutes in chiral liquid crystals

Abstract

International audienceThe splitting of signals in the NMR spectra originating from enantiotopic sites in prochiral moleculeswhen dissolved in chiral solvents is referred to as spectral enantiotopic discrimination. This phenomenonis particularly noticeable in chiral liquid crystals (CLCs) due to the combined effect of the anisotropicmagnetic interactions and the ordering of the solute in the mesophase. The enantiorecognitionmechanisms are different for rigid and flexible solutes. For the former, discrimination results fromsymmetry breaking and is restricted to solutes whose point groups belong to one of the following four(‘‘allowed’’) symmetries, Cs, C2v, D2d and S4. The nature of the symmetry breaking for each one of thesegroups is discussed and experimental examples, using mainly 2H 1D/2D-NMR in chiral polypeptide lyotropicmesophases, are presented and analyzed. When flexible optically active solutes undergo fast racemization (onthe NMR timescale) their spectrum corresponds to that of an average prochiral molecule and may exhibitenantiotopic sites. In CLCs, such sites will become discriminated, irrespective of their average (improper)symmetry. This enantiodiscrimination results mainly from the different ordering of the interchangingenantiomers. Several examples of such flexible molecules, including solutes with average axial and planarsymmetries, are commented. Dynamic processes in solution that are not accompanied by the modulation ofmagnetic interactions remain ‘‘NMR blind’’. This is sometimes the case for interconversion of enantiomers(racemization) or exchange of enantiotopic sites in isotropic solvents. The limitation can be lifted by usingCLCs. In such solvents, non-equivalence between enantiomers or between enantiotopic sites is induced bythe chiral environment, thus providing the necessary interactions to be modulated by the dynamic processes.Illustrative examples involving exchange of both, enantiotopic sites and enantiomers are examined. Inthis comprehensive review, various important aspects of enantiodiscrimination by NMR are presented.Thus the possibility to reveal enantiotopic recognition using residual dipolar couplings or to determinethe absolute configuration of enantiotopic NMR signals is discussed. The various kinds of chiralmesophases able to reveal enantiotopic discrimination in guest prochiral molecules are also describedand compared with each other. Finally to illustrate the high analytical potentialities of NMR in CLCs,several and various applications involving the enantiodiscrimination phenomenon are described.A strategy for assigning the NMR signals of meso compound in a meso–threo mixture of cyclic moleculesis first discussed. This is followed by a description of advantages of the method for the determination of(D/H) natural isotopic fractionation in biocompounds