Chiral carriers

Addition of a chiral carrier can improve the enantioselective transport through the membrane by preferentially forming a complex with one enantiomer. Typically, chiral selectors such as cyclodextrins (e.g. (4)) and crown ethers (e.g. (5) [21]) are applied. Due to the apolar character of the inner surface and the hydrophilic external surface of cyclodextrins, these molecules are able to transport apolar compounds through an aqueous phase to an organic phase, whereas the opposite mechanism is valid for crown ethers. 

FIGURE 1.35 SLM process using O-9-(l-adamantylcarbamoyl)-10,ll-dihydro-ll-octadecylsulfinylquinme and corresponding quinidine derivative as chiral carriers for the preparative separation of enantiomers of Al-derivatized amino acids (e.g., DNB-Leu). (a) ftinciple of the carrier SLM process with carrier-mediated transport (top) and (nonstereoselective) nonspecific transport processes (bottom), (b) General experimental setup of the SLM production unit with two membrane modules, (c) Multistage SLM purification process. P, permeate QD/QN, membrane modnles snpported with quinidine-derived and quinine-derived chiral carriers. R, S, D, L refers to the respective enantiomers of the selectand (DNB-Leu). (Reproduced from A. Maximini et al., J. Membr. ScL, 276 221 (2006). With permission.)... 

The first successful experiments were reported by Schwab [16] Cu, Ni and Pt on quartz HI were used to dehydrogenate racemic 2-butanol 23. At low conversions, a measurable optical rotation of the reaction solution indicated that one enantiomer of 23 had reacted preferentially (eeright-handed quartz gave the opposite optical rotation it was deduced that the chiral arrangement of the crystal was indeed responsible for this kinetic resolution (for a review see [8]). Later, natural fibres like silk fibroin H5 (Akabori [21]), polysaccharides H8 (Balandin [23]) and cellulose H12 (Harada [29]) were employed as chiral carriers or as protective polymer for several metals. With the exception of Pd/silk fibroin HS, where ee s up to 66% were reported, the optical yields observed for catalysts from natural or synthetic (H8, Hll. H13) chiral supports were very low and it was later found that the results observed with HS were not reproducible [4],... 

Chiral crown-ethers were originally developed to be used as chiral carriers in enantios-elective liquid-liquid extraction and/or as chiral phase transfer catalysts. The principle of stereoselective host-guest complexation with a chiral crown-ether type host and its application to LC has been first described in 1978 by Cram and co-workers [ 12. Currently, crown-ether type CSPs. which incorporate atropisomeric binaphthyl derivatives as chiral units incorporated in a 18-crown-6 type backbone with substituents that enforce discrimination between enantiomers are commercially available as Crownpak CR (-I-) and (—) (Daicel Chemical Ind.) (see Fig. 9.23a). 

One important advantage of charged CD derivatives is their use as chiral carriers [5,6,8,10-12]. This enables one to mobilize a neutral analyte even in the absence of the EOF, a charged analyte in the opposite direction to its electrophoretic mobility, and to suppress a mobility of an analyte in the uncomplexed form. The last offers a significant advantage for the improvement of a separation selectivity. 

Fig. 1 Simultaneous separation and enantioseparation of thalidomide, 5-hydroxythalidomide, and 5 -hydroxythalidomide in CE using polyacrylamide-coated capillary and a mixture of 15 mg/mL sulfobutyl (4.0)-/3-CD and 10 mg/mL (3-CD as the chiral carrier.

Several attempts to perform enantioselective separations using membranes of a chiral mobile carrier have been reported and have been extensively discussed in a recent review [185]. Various chiral carriers, mainly crown ethers, were used for this purpose but poor enantioselectivity was usually obtained and no preparative application has been described. 

The most extensively examined method of stereoselective SLM separation is carrier-facilitated transport with chiral carriers. Different macrocychc compounds, transition metal complexes, phosphates, lariat ethers, podands. 

An interesting group of chiral carriers are those formed by species that utilize interactions between transported enantiomer and transition metal complexes. For instance, such a compound, acting as an additional chiral ligand for the copper central cation, is able to recognize an amino acid Cu(II) complex present in the feed phase. This double chiral carrier-amino acid-Cu (II) complex becomes diastereoisomeric and can be transported through a... 

Other classes of substances tested as potential chiral carriers in SLMs are dialkyl and monoalkyl phosphates, phosphonates, and phosphinates based on (—)-menthol and (—)-nopol [43]. The amino acids are transported... 

For characterization and exploitation of the diamide-phase system, a chiral diamide, e,g., (Ill) was examined as a modifier in the mobile phase (solvent) in conjunction with a non-bonded (bare) silica. Such a chiral carrier separated enantiomeric N-acyl-d-amino acid esters and amides with separation factors comparable to those for bonded stationary phase systems. The resolution can be as cribed to diastereomeric complexation through amide-amide hydrogen bonding between the amide additive and enantiomeric solute molecules in the carrier solvent, followed by separation of the diastereomeric complexes by the (achiral) silica phase. This process should be applicable as widely as that involving chiral diamide-bonded stationary phase systems. 

Another complicating factor is that the surface of quartz is the only asymmetric factor in the metal-quartz catalysis and its specific areas in most cases were very small (only 44 cm /g " ). This coupled with the fact that the amount of metal deposited on quartz was rather high, so the extent of racemization of butanol during reaction would be high, which detracts from the effectiveness of the catalyst. Thus, quartz appeared not to be an effective chiral carrier for catalysis or adsorption in asymmetric experiments. Nevertheless, in general the data using quartz crystals are of interest and received positive evaluations in several publications... 

Chapter 3 presents data about enantioselective hydrogenation reactions on metal catalysts supported on chiral carriers. Discussed are palladium supported on modified silica gels, effective chiral colloidal catalysts, template catalytic systems, palladium-silk, palladium-wool, and palladium polypeptide catalysts. 

This book contains many publications which represent analyses of the steps of elaboration of effective heterogeneous enantioselective hydrogenation catalysts, of their significant role in the theory of catalysis, and of their role in the practice of asymmetric catalysis. In addition to reviewing the first works on catal Tic hydrogenation of C=C double bond in prochiral compounds on metal catalysts supported on chiral carriers, which admittedly have only historical interest, the Chapters 1-3 review data on asymmetric adsorption of enantiomers and separation of racemic mixtures on organic and inorganic adsorbents. 

Diels-Alder reactions of 6 and 8 with butadiene and 2,3-dimethylbutadiene under thermal conditions led to the expected mixtures of diastereomers 11a,b-14a,b. Reaction of 6 and 8 with 2-trimethylsilyloxybutadiene proceeded, however with full regioselectivity and afforded mixtures of 15a,b and 16a,b after desilylation. (Figure 5.) Due to the presence of the chiral carrier a moderate diastereoselection could be observed in some cases. The diastereomeric mixtures could be separated only in the case of 16a,b. The configurations of C-2 in the thiopyran part of lla,b-16a,b could not be deduced from the NMR spectra. In order to prove the structures of 15a,b and 16a,b we have used Raney-Ni desulfurization to get the expected 5-ketohexanoate esters (Figure 6.). 

By using cyanoformate esters as electrophiles, Johnson and coworkers were able to employ catalytic amounts of the cyanide initiator in reactions with acyl silanes. This process led to carbon-carbon bond formation via C-acylation. For example, acyl silane 61 and ethylcyanoformate combined under these conditions to provide the tertiary alcohol silyl ether 62 in nearly quantitative yield. Johnson s group has also developed an asymmetric version of this process, utilizing the Jacobsen (salen)aluminum system as a chiral carrier for the cyanide anion. ... 

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