Chiral donor-acceptor-type

The slow nucleophilic addition of dialkylzinc reagents to aldehydes can be accelerated by chiral amino alcohols, producing secondary alcohols of high enantiomeric purity. The catalysis and stereochemistry can be interpreted satisfactorily in terms of a six-membered cyclic transition state assembly [46,47], In the absence of amino alcohol, dialkylzincs and benzaldehyde have weak donor-acceptor-type interactions. When amino alcohol and dialkylzinc are mixed, the zinc atom acts as a Lewis acid and activates the carbonyl of the aldehyde. Zinc in this amino alcohol-zinc complex is regarded as a kind of chirally modified Lewis acid. Various kinds of polymer-supported chiral amino alcohol have recently been prepared and used as ligands in dialkylzinc alkylation of aldehydes. 

Donor-acceptor-type CSPs capitalize on synthetic or semi-synthetic chiral low-mo-lecular-weight SOs capable of enantioselectively recognizing analytes by complementary arrays of nonionic attractive interactions [67]. The repertoire of fhese nonionic interactions generally comprises hydrogen bonding, jt-k-s lack ing, di-pole-dipole-slacking and steric interactions. 

Disadvantages of donor-acceptor type CSPs are their rather limited scope of application and incompatibility with polar-organic and reversed-phase mobile phase conditions. Thus, the spatially well-defined, but restricted functional group repertoires of donor-acceptor-type SOs can satisfy the chiral recognition requirements of a few classes of analytes only. In addition, to produce useful levels of enantioselectivity with donor-acceptor-type CSPs, analytes may frequently require dedicated (achiral) derivatization to attenuate basicity/acidity and/or to complement... 

New brush-type phases (donor-acceptor interactions) are appearing all the time. " Examples are stationary phases comprising quinine derivatives and trichloro-dicyanophenyl-L-a-amino acids as chiral selectors. Quinine carbamates, which are suitable for the separation of acidic molecules through an ionic interaction with the basic quinine group, are also commonly used but in general they are classified with the anion-exchange type of chiral selectors (see further) because of their interaction mechanism, even though r-donor, r-acceptor properties occur. (Some separations on Pirkle-type CSPs are shown in Table 2.)... 

Such polyacrylamide type CSPs are best operated under normal-phase conditions (usually u-hexane with a polar modifier like alcohols, dioxane, THF, etc.). The spectrum of applicability includes a wide variety of drug substances with hydrogen donor-acceptor and aromatic groups. Other groups also prepared CSPs from chiral (meth)acrylamide monomers with various chiral amino components. An extensive review on this topic was published by Kinkel 47j. 

Parallel to the n-donor-acceptor CSPs related to Pirkle s pioneering work for the understanding of chiral recognition phenomena and for gaining insight into SO-SA complexation principles on the molecular level, the protein type CSPs can claim a major credit for the rapid development of chiral technology in pharmaceutical and life sciences. 

Most chiral HPLC analyses are performed on CSPs. General classification of CSPs and rules for which columns may be most appropriate for a given separation, based on solute structure, have been described in detail elsewhere. Nominally, CSPs fall into four primary categories (there are additional lesser used approaches) donor-acceptor (Pirkle) type, polymer-based carbohydrates, inclusion complexation type, and protein based. Examples of each CSP type, along with the proposed chiral recognition mechanism, analyte requirement(s), and mode of operation, are given in Table 3. Normal-phase operation indicates that solute elution is promoted by the addition of polar solvent, whereas in reversed-phase operation elution is promoted by a decrease in mobile-phase polarity. 

Here, only general categories of chiral stationary phases will be mentioned. One of the more popular types of GC and HPLC columns use donor-acceptor interactions such as those illustrated in Figure 2.16 for enantiomer separation. 

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