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

Abstract

The splitting of signals in the NMR spectra originating from enantiotopic sites in prochiral molecules when dissolved in chiral solvents is referred to as spectral enantiotopic discrimination. This phenomenon is particularly noticeable in chiral liquid crystals (CLCs) due to the combined effect of the anisotropic magnetic interactions and the ordering of the solute in the mesophase. The enantiorecognition mechanisms are different for rigid and flexible solutes. For the former, discrimination results from symmetry 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 these groups is discussed and experimental examples, using mainly (2)H 1D/2D-NMR in chiral polypeptide lyotropic mesophases, are presented and analyzed. When flexible optically active solutes undergo fast racemization (on the NMR timescale) their spectrum corresponds to that of an average prochiral molecule and may exhibit enantiotopic sites. In CLCs, such sites will become discriminated, irrespective of their average (improper) symmetry. This enantiodiscrimination results mainly from the different ordering of the interchanging enantiomers. Several examples of such flexible molecules, including solutes with average axial and planar symmetries, are commented. Dynamic processes in solution that are not accompanied by the modulation of magnetic 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 using CLCs. In such solvents, non-equivalence between enantiomers or between enantiotopic sites is induced by the 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. In this comprehensive review, various important aspects of enantiodiscrimination by NMR are presented. Thus the possibility to reveal enantiotopic recognition using residual dipolar couplings or to determine the absolute configuration of enantiotopic NMR signals is discussed. The various kinds of chiral mesophases able to reveal enantiotopic discrimination in guest prochiral molecules are also described and 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 molecules is first discussed. This is followed by a description of advantages of the method for the determination of (D/H) natural isotopic fractionation in biocompounds.

Synthesis and Stereochemical Assignment of Crypto‐Optically Active 2H6‐Neopentane

“…Thus,the presence of three 2 1 Hd ecoupling is turned off (see also the Supporting Information). Considering the positive results for the determination of the enantiomeric ratio of (S)-2 H 3 -2,and previous studies on isotopic enantiodiscrimination, [19]2 H-{ 1 H} NMR in PBLG mesophases,w eapplied the same technique again to differentiate the enantiomeric signals of (rac)-2 H 6 -1, with the goal of assessing the enantiopurity of enantioenriched (S)-2 H 6 -1.I nterestingly,s mall but spectrally resolved quadrupolar doublets (j Dn Q j< 2Hz) associated with the mono-and dideuterated methyl groups (see the Supporting Information) indicate that this asymmetric (C 1 point group) molecule is slightly oriented in this weakly aligning lyotropic chiral mesophase.Unfortunately,all attempts to discriminate the enantiomers based on RQC differences failed, irrespective of the temperature (in arange of 30 K) and the polarity of the cosolvent (CHCl 3 or pyridine). It appears that the overall shape recognition mechanisms involved in the chiral discrimination phenomenon [22] are in the case of PBLG unable to differentiate the extremely small topological differences between the mono-, di-, and trideuterated methyl groups around the stereogenic carbon atom of 2 H 6 -1.…”

Perspectives in the application of residual dipolar couplings in the structure elucidation of weakly aligned small molecules

“…This is particularly important for systems involved in studies of the interaction of (homo)chiral media with the two enantiomeric forms of a small molecule. These studies are not only used for determination of enantiomeric excess, but are often undertaken to improve the understanding of the molecular interactions and processes involved in the alignment of the small molecule . While not yet possible with sufficient accuracy, if methods are found to predictively model these interactions in, e.g.…”

Synthese und stereochemische Bestimmung von krypto‐optisch‐aktivem 2H6‐Neopentan

“…[16] Die Bestimmung des Enantiomerenverhältnisses von 2 H 3 -2 erfolgte durch protonenentkoppelte Deuterium-NMR( 2 H-{ 1 H})-Messungen unter Verwendung eines lyotropen Polypeptid-CLC aus Poly-g-benzyl-l-glutamat (PBLG) und Chloroform als organisches Lçsungsmittel. [18][19][20] [22] im Fall von PBLG nicht erfolgreich, und extrem kleine topologische Unterschiede zwischen einfach, zweifach und dreifach deuterierten Methylgruppen am stereogenen Kohlenstoffzentrum von 2 H 6 -1 waren nicht aufzulçsen. [11] Diese NMR-Methode zur exakten Bestimmung der Enantiomerenreinheit (e.r.…”