DUDDECK AND DIAZ GOMEZ CH. 0,31GR △8 0.6 0,8 0,2 -0,3 2尚 0.4J y.com. reliable in that sense Very tion of enantiomenc Here the bindin to provide positive results. cific contacts between the functional g ponen the CONCLUSION ase Methods of chiral recognition are multifaceted,and it CLsR)Pirkdle' and particular how the s of the ac of a sub etc.),metalc e CDAS CDA-derivatives are nformationally flexible.it is not the atoms e.g.,in oxi T-oxano G hod is in such cas this holds efor a safe AC prediction that the su are aceeigtcDenmdcaessaneotro0n NOE. inambiguously.Mosher acid esters or amides with CH,O OCH 66 67 68 69 Scheme2.Structures ofchrace6-70ertiaedby thedihdum methd ChiraiyDO110.1002/chir mers of a given compound with those calculated by DFT GIAO method was sufficient to identify the correct abso￾lute conformation;119 a X-ray diffraction experiment sup￾ported this result. Very recently, a comprehensive review describing theory and application of chiral recognition in nonisotropic phases has been published.120 So far, however, there seems to be no such solid state study on ether compounds although at least some of those techniques should be able to provide positive results. CONCLUSION Methods of chiral recognition are multifaceted,24 and it is not easy to find the most suitable auxiliary for a given substrate. Nevertheless, some general guidelines can be ascertained. If the determination of the AC of a substrate is the goal, the preparation of diastereomeric derivative using enantio￾pure CDAs is the method of choice. Excellent CDAs for alcohols, amines, and carboxylic acids are available but they are less common for most other functional groups or less reactive substrate; safe CDAs for ethers do not exist. It is of great importance to keep in mind that there is a principal problem in this kind of experiment. Since most CDA-derivatives are conformationally flexible, it is not the AC of the substrate-CDA molecule which has to be deter￾mined but rather the absolute conformation. Therefore, it is of vital importance for a safe AC prediction that the sub￾strate-CDA molecules tend to adopt one single, strongly preferred conformation so that any space-specific through￾space effects (chemical shift anisotropy, NOE, etc.) between the CDA- and the substrate-part can be assigned unambiguously. Mosher acid esters or amides24,62–65 with the anisotropic phenyl group is quite reliable in that sense; Harada’s MaNP esters66,67 seems to be even better. The majority of practical application is focussed on the discrimination of enantiomers by CSAs for the determina￾tion of enantiomeric excess (e.e.). Here, the binding between the substrate/solute and the CSA is much weaker but still strong enough to produce NMR signal dif￾ferentiation (diastereomeric dispersion). Formation of spe￾cific contacts between the functional groups of both com￾ponents—the more, the better—is desirable because this generally helps to reduce the mobility and, thereby, increase the extent of differentiation. If the functional group of the substrate is a hard Lewis base (alcohols, amines, carbonyls), Pirkle’s CSA21–26 and particularly CLSR21–24,27 are recommended. In case, however, the sub￾strate is a soft Lewis base (phosphanes, sulfides, sele￾nides, olefins, etc.), metal complexes such as Rh2[MTPA]4 are optimal because those metal ions are soft Lewis acids.30 There is a number of functional groups which do not react well with both types of NMR auxialiaries, hard and soft Lewis acids. This review is devoted to one of them, the ethers. If the ether oxygen is not sterically shielded by hydrogen atoms, e.g., in oxiranes or 7-oxanorbornanes, CLSR and sometimes even CSA can be used. Generally, however, the dirhodium method is superior in such cases; this holds for olefins also.87 Other approaches exploit guest–host interactions by ac￾commodating one enantiomer better in a given supramo￾lecular cavity than the other. Examples are cyclodex￾trins,24,103–108 chiral crown ethers, and calixarenes but also liquid crystalline polypeptides109–112 embedding the sub￾strate in a partially ordered array (chiral hosting auxilia￾Scheme 24. Density functional (B3LYP 6-31G*) calculated31 highest occupied molecular orbital (HOMO) of 4-chloroanisol. [Color figure can be viewed in the online issue, which is available at www.interscience. wiley.com.] Scheme 25. 13C complexation induced shifts (Dd) of the atoms C-20 /60 in the ethers 61–65 (in ppm) plotted against the r0 R-parameters of the substituents X (F, Cl, Br, I, NO2).100 Scheme 26. Structures of chiral acetals 66–70 enantiodifferentiated by the dirhodium method. 64 DUDDECK AND DI´AZ GO´ MEZ Chirality DOI 10.1002/chir