Chiral axes

Among other approaches not based directly on pairwise interactions there is the statistical mechanics of solutions in which the constituents axe chiral molecules, treated by extension of the hard-sphere or other approximations. This is also more or less imexplored, and there are only the briefest of references in Section V. 

Microcrystalline cellulose triacetate, cyclodextrin- and crown ether-derived CSPs, as well as some chiral synthetic polymers, achieve enantiomer separation primarily by forming host-guest complexes with the analyte in these cases, donor-acceptor interactions are secondary. Solutes resolved on cyclodextrins and other hydrophobic cavity CSPs often have aromatic or polar substituents at a stereocenter, but these CSPs may also separate compounds that have chiral axes. Chiral crown ether CSPs resolve protonated primary amines. 

In principle, all forms of chirality have been used for liquid crystal synthesis. This involves compounds with single chiral centers, multiple chiral centers, chiral axes, chirality planes, etc. For example, chiral methylidencyclohex-anes can be found in [24], chiral aliens in [25], and binaphthyls in [26]. 

If a solute of the general formula AX (A is the chiral ion and X is an achiral ion) dissociates completely into ions once dissolved, then the solubility of the racemic conglomerate, SR, is equal to n%V2-SA (where SA is concentration of A in a solution saturated with AX ). If the solute is of the type AX, then 5 = V2-5a. The subscript n refers to the achiral ion and may be fractional, and so A2X must be represented by AXi/. If dissociation of AX is incomplete, SA lies between n i/2-SA and 2SA. For weakly dissociated electrolytes (such as carboxylic acids), SR is approximately 2SA. 

FIGURE 1.2 Structure and stereochemistry of commercially available cinchona alkaloid CSPs, marketed under trade name CHIRALPAK by chiral technologies europe. QN denotes quinine- and QD quinidine-derived and AX refers to their anion-exchanger capabilities vide infra). 

FIGURE 1.3 Enantiomer separation of the chiral acid iV-acetyl-a-allyl-glycine on CHIR-ALPAK QN-AX (a) and CHIRALPAK QD-AX (b) by an enantioselective anion-exchange retention process. Chromatographic conditions Column dimension, 150 x 4 mm ID eluent, 1 % (v/v) glacial acetic acid in methanol flow rate, 1 mLmin temperature, 25°C detection, UV 230 nm. (Reproduced from M. Lammerhofer, et ah, Nachrichten aus der Chemie, 50 1037 (2002). With permission.)... 

Meanwhile, a wide variety of cinchona alkaloid derivatives have been systematically developed as chiral selectors, which complement each other in their enantiomer discrimination profiles. Considering the variety of derivatives, an overall reasonably broad applicability spectrum, approximating for chiral acids a 100% success rate, is yielded and extreme enantiorecognition levels (a-values above 15) could be realized for some chiral solutes with certain selectors. Moreover, various studies carried out with the CHIRALPAK QD/QN-AX columns in industry and academia clearly document their practical usefulness for solving challenging real-life problems and this should be illustrated by the present review article as well. 

Figure 1.4. Chiral environment of an (i )-BINAP-transition metal complex (M = metallic element, ax = axial, eq = equatorial = coordination site in the plane ...

Chiral compounds are of wide interest as auxiliaries in asymmetric synthesis. The efficiency of the auxiliary in the process is usually expressed as the ee of the product (eCpfod)- What happens if the chiral auxiliary is not enantiomerically pure One expects a lower ee for the product. From this value one can calculate the maximum ee of the product (eCj ax) by taking into account the enantiomeric excess of the auxiliary, assuming a proportionality between eCprod and eeaux ... 

The erythro/threo diastereomers of a larger variety of 4,5-disubstituted 1,3-dioxanes (chiral conformationally restricted arachidonic acid analogs 54-59) proved to be of enantiomerically pure stereochemistry (cf. Scheme 17) (99TA139) the epimers were clearly identified by the coupling patterns of the protons in positions 4, 5, and 6, reflecting the ax,equ (threo) and equ,equ (erythro) relationships of the two substituents. 

At low temperature the 13C NMR spectra of these geminal methyls consisted of clean 1 1 doublets for each of the compounds. Diastereotopic methyls established the chiral characters of these three compounds. Above 170 K, with increasing temperature there was progressive averaging of these doublets. Phenomenologically, this implied the operation of transfer of coordinated TMEDA between faces of the allyl plane which is, overall, inversion. The process is first order in the allylic lithium compound. The activation parameters are typically A// of 5 to 7 kcal mol 1 with a large negative AX of ca —25 5 eu... 

Many prochiral groups, however, cannot be interchanged by any type of symmetry operation, because of the presence of one or more chiral centers in the molecule. They are diastereotopic and anisochronous, and they constitute AB, AX, etc., systems. For this reason, when encountering prochiral groups, chemists should expect them to be diastereotopic and should be, perhaps, pleasantly surprised when they are not. 

Fig. 7.22 (A) Chemical structures of the quinine and quinidine tert-butylcarbamate-based CHIRALPAK QN-AX and CHIRALPAK QD-AX anion exchange-type CSPs. These CSPs show pseudo-enantiomeric chiral recognition pro-...

MARCH-INSIDE descriptors are derived from the different kth powers of the electron-transition stochastic matrix, denoted as H, which is a stochastic matrix of dimension Ax A derived from the —> dectronegativity-weighted a acency matrix A, modified by a 3D central chirality factor to [Gonzalez Diaz, Sanchez et al., 2003], as... 

Figure 6.21. Titanium TADDOLate - crotyloxazolidinone complexes. The dioxolane ring of the chiral ligand (Figure 6.18h) is deleted for clarity, and the phenyl groups are labelled as axial (ax) or equatorial (eq). (a) Symmetrical complex found by NMR to be the predominant species in solution [237], and also characterized crystallographically [238]. (b) Complex judged to be most likely to be responsible for the asymmetic cycloaddition [228,237]. (c) This complex is probably less reactive, since approach of the dienophile is hindered by the axial phenyl [228].

Nakanishi s method is based on the splitting of CD waves when two chromopho-res on a chiral molecule are close in space (the dibenzoate rule). Such is the case with dibromobenzoates of sugars which have a 1,2 or 1,3 relationship. In the first version of the method, saponins were permethylated, methanolyzed with acid and the liberated OH positions were p-bromobenzoylated (44). As terminal sugars are fully methylated and UV transparent, they need not be considered. Branched sugars (two substitutions at least) 3deld di-or tri-benzoates with exciton-split CD curves. The difference in Ae values of the two extrema of split CD curves is directly related to the respective positions of the benzoates (1, 2 eq-eq = 1, 2 eq-ax = 62 1, 2 ax-ax = 6 1, 3 eq-eq = 0 1, 3 eq-ax = 16). The sensitivity of circular dichroism makes the method suitable for microassays. Typical analyses are performed on a 100 pg scale (nanomolar levels). 

Sinha and Keinan have reported a second synthesis of 100, which makes use not of building blocks, but of auxiliaries from the chiral C pool (AX as well as ent-AX). The synthesis begins with a reaction sequence that follows the Ci3 + C2 + Cj pattern to convert the C13 aldehyde into the hydrocarbon. This is then transformed by a threefold Sharpless asymmetric dihydrox-ylation (and partial acetalization) into the highly functionalized Cjg intermediate. The latter compound, after another chain elongation by means of the same C2 building block as used earlier, furnishes the Cig intermediate, and this then provides 100 by a three-step route (Scheme 49). 

DAIB =((-)-3-exo-(Dimethylamino)isobomeol) was introduced as a chiral auxiliary (AX) for the enantioselective addition of dialkylzincs to aldehydes [112]. It has been applied for both intermolecular [113a] and intramolecular [113b] formation of ( -aIlyl alcohols from acetylenes and aldehydes via (l-alkenyl)(alkyl)zinc intermediates. 

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