DUDDECK AND DIAZ GOMEZ 0-CHa 人CH quite CH requre more comple 57 nation of enantiomeric ethers CH2 er rim. xtrins have auxiliary.and this has be ecoa是时a is not a major 营 arat aturated molccules.the HOMO-LUMO on be een the ether in the the magnitudes of the chi ions and the signal dispe o he the thers in a parallel way.Unfo ethers withou gen but ther -carbons (C-2/6) h er exte nle hane山ers with and the parameters of -although inte ode of don Cour as w t66-70(Sch poly-y-b he nding in CLSR pieandresidua -are ou W-pol Contributions to△△S 54 -o 56 Both a C symmetry:no change Sgemental mobility retained tosomeexte High AAs(negative）→large AAG Moderate AAS (negative)small AAG Chirality DOI 10.1002/chir ability of the ether oxygen atom is modulated by the para￾substituent. This is not surprising when the HOMOs of those molecules are inspected (Scheme 24); note that in un￾saturated molecules, the HOMO-LUMO energy has a major influence on the paramagnetic contribution of the nuclear 13C shielding constant which, in turn, dominates the total shielding.101 Any inductive interaction between the ether ox￾ygen and a dirhodium atom will influence the para-substitu￾ent, and, vice versa, any resonance effect of the para-substit￾uent will influence the donor property of the oxygen. Interestingly, among the aromatic carbons it is not the oxygenated one (ipso) showing a complexation induced shift, which would indicate an inductive effect of the oxy￾gen, but the ortho-carbons (C-20 /60 ) and—to a somewhat lesser extent—the para-carbons (C-40 ).100 This finding and the good correlation between the C-20 /60 complexation induced shifts and the -parameters of X102 (Scheme 25) confirm the aforementioned resonance interaction model of donor ability modulation. The dirhodium method works satisfactorily with acetals as well. This has been demonstrated for a variety of chiral acetals 66–70 (Scheme 26).98 Miscellaneous NMR methods. The aforementioned classes of auxiliaries—CSA, CLSR, and the dirhodium complex—are outstanding in their wide and easy applica￾tion. However, many other successful examples of chiral NMR auxiliaries exist in the literature24 but they are often quite specific to the particular substrates investigated or require more complex NMR techniques. Most of those techniques allow, at least in principle, the chiral discrimi￾nation of enantiomeric ethers. Cyclodextrins (CDs) are cyclic oligo-D-glucosides and form basket-shaped cones with differently sized openings; the CH2OH residues are oriented at the smaller rim. The cones can be customized by the number of glucose units (a-, b-, g-CDs), and many derivatized cyclodextrins have been introduced.24 CDs have found widespread use as a chiral auxiliary, and this has been summarized.31–33,103 Their efficiency is based on the fact that one enantiomer fits into the CD cavity whereas the other one does not; for￾mation of specific bindings by polar groups is not a major mechanism. Therefore, it is not surprising that even unpo￾lar compounds could be resolved by CD-CSA; examples are cis-decalin (71) 104 and a-pinene (72).105 During an extensive study on the chromatographic sep￾aration of various chiral fluorinated inhalation anesthetics, e.g., 73, 74, and 75 (see Scheme 26), Schurig et al. reported that these haloethers can also be differentiated by 1 H and 19F NMR spectroscopy when g-cyclodextrin derivatives are added as auxiliaries.106–108 They found a rough correspondence between the magnitudes of the chi￾ral separation factors a in the chromatographic separa￾tions and the signal dispersions in the 1 H and 19F NMR spectra; both depend on the free binding energy.108 This means that both techniques react to the donor abilities of the ethers in a parallel way. Unfortunately, ethers without any halogens have apparently not been subjected to analo￾gous experiments so that it remains open whether or not the success of fluorinated ethers depends on the fact that they are stronger donors than ethers without fluorine(s). A remarkable resolving technique—although experi￾mentally complex—is the NMR measurement of a chiral substrate in a chiral lyotropic liquid crystal.109,110 In Cour￾tieu’s experiments,109 chiral substrate molecules ex￾perience a differential ordering effect by interacting with poly-g-benzyl-L-glutamate (PBLG), and the enantiomers respond by differences in the NMR observables, such as chemical shift anisotropies and residual dipolar couplings. This method can be applied successfully to low-polarity Scheme 22. Prototypic ether structures 56–58 (top); NMR signals of 56 in the presence of an equimolar amount of 52 (bottom); left: H-1, Dm 5 6 Hz, 3 J(H-1,H-2) 5 6.4 Hz; right: C-10 (Dm 5 23 Hz).97 TABLE 3. Estimation of the activation energy DDS# in the adduct formation equilibrium of the dirhodium complex 52 and the ethers 54 and 56 in terms of charges in symmetry ion and mobility restriction98 Contributions to DDS# Mixing entropy (racemates) Both are recemates; no difference Symmetry loss Total loss of C3 symmetry C1 symmetry; no change Mobility restriction: overall motion Reduction of overall mobility to adduct mobility; no major difference Mobility restriction: Isotropic/ segmental motion Total loss of isotropic mobility Sgemental mobility retained to some extent Consequences High DDS# (negative) ? large DDG# Moderate DDS# (negative) ? small DDG# 62 DUDDECK AND DI´AZ GO´ MEZ Chirality DOI 10.1002/chir