Enantioselective anion exchange

A stoichiometric model can conveniently be invoked to explain the ion-exchange retention process [43 6]. As discussed in detail in these cited papers on ion-exchange theory, useful information about the involved ion-exchange process can be deduced from plots of log k vs. the log of the counterion concentration [X], which commonly show linear dependencies according to the stoichiometric displacement model (Equation 1.1) 

In this equation, the constant Kz, which can be easily inferred from the intercept, represents a system-specific constant that is related to the ion-exchange equilibrium constant K(Lmol ), the surface area 5 (in m the charge density on the surface, that is, the number of ion-exchange sites qx available for adsorption (in molm ), and the mobile phase volume Vo (in L) in the column as described by the following equation  

FIGURE 1.4 Dependencies of retention factors k on counterion (i.e., phosphate) concentration [X]. Experimental conditions Mobile phase, methanol-sodium dihydrogenphosphate buffer (50 50 v/v) (pHa 6.5 adjusted in the mixture with sodium hydroxide) flow rate, 1 mLmin temperature, 25°C CSP, 0-9-[3-(triethoxysilyl)propylcarbamoyl]-quinine bonded to silica [30] column dimension, 150 x 4 mm ID. 

FIGURE 1.5 pH -effect on retention factors k and separation factors a. CSP 0-9- tert-butylcarbamoyl)quinine bonded to sihca column dimension, 150 x 4 mm ID eluent, methanol-ammonium acetate buffer (80 20, v/v) (adjusted with acetic acid) temperature, 25°C 1 mL min sample, N-benzoyl-leucine (Bz-Leu). (Reproduced from M. Lammerhofer et al., American Laboratory, 30 71 (1998). With permission.) 

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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.)... 

Maier, N. M., Nicoletti, L, Lammerhofer, M., Lindner,W. Enantioselective anion exchangers based on cinchona alkaloid-derived carbamates influence of C8/C9 stereochemistry on chiral recognition, Chirality, 1999,11, 522-528. 

A poly-L-lysine coating of a Ti02 gel film, was used to bind anionic fluorophores (sulforhodamine-B or carboxyfluorescein) by electrostatic interactions. Enantioselective anion exchange was observed when this solid material was exposed to a solution containing d- or L-glutamic acid (10 pM), with a fluorescence increase, due to the release of the fluorophore in the solution, which was found to be higher when using d-G1u [96]. 

Paul S, Huang J, Ichinose I (2005) Enantioselective anion exchange on a positively charged poly(L-lysine) layer assembled on thin Xi02-gel Aims. New J Chem 29 1058-1063... 

Reischl RJ, Hartmanova L, Carrozzo M, Huszar M, Fruhauf P, Lindner W. Chemoselective and enantioselective analysis of proteinogenic amino acids utilizing N-derivatization and 1-D enantioselective anion-exchange chromatography in combination with tandem mass spectrometric detection. J Chromatogr A 2011 1218 8379—87. 

Early examples of enantioselective extractions are the resolution of a-aminoalco-hol salts, such as norephedrine, with lipophilic anions (hexafluorophosphate ion) [184-186] by partition between aqueous and lipophilic phases containing esters of tartaric acid [184-188]. Alkyl derivatives of proline and hydroxyproline with cupric ions showed chiral discrimination abilities for the resolution of neutral amino acid enantiomers in n-butanol/water systems [121, 178, 189-192]. On the other hand, chiral crown ethers are classical selectors utilized for enantioseparations, due to their interesting recognition abilities [171, 178]. However, the large number of steps often required for their synthesis [182] and, consequently, their cost as well as their limited loadability makes them not very suitable for preparative purposes. Examples of ligand-exchange [193] or anion-exchange selectors [183] able to discriminate amino acid derivatives have also been described. 

One important point to stress from these results is the possibihty of using copper chloride instead of copper triflate to prepare the complexes. It is well known that in organic solvents there is a dramatic counteranion effect on the activity and enantioselectivity of these catalysts. On the other hand, the rapid anion exchange produced in the ionic hquid resulted in better performance of the complexes, as the bis(triflyl)imide behaves in a similar way to the triflate counteranion. 

Monolithic columns with the chiral anion exchange-type selectors incorporated into the polymer matrix obtained through in situ copolymerization process of a chiral monomer (in situ approach) [80-83,85] or attached to the surface of a reactive monolith in a subsequent derivatization step (postmodification strategy) [84], both turned out to be viable routes to enantioselective macroporous monolithic columns devoid of the limitations of packed columns mentioned earlier. 

Recently, Lindner and coworkers developed a series of anion-exchange CSPs based on quinine and quinidine as chiral selectors (Fig. 6.11) [79, 80]. These phases are particularly appropriate for the separation of the enantiomers of chiral acidic compounds. Improvement of the chiral recognition power of these phases by rationally designed structural modifications has led to exceptionally high enantioselectivity which, of course, is of great interest for preparative applications [81]. Screen-... 

Enantioselective epoxidation. This effective catalyst (1) is readily prepared in a 70-100 kg scale from the resolved diamine (with tartaric acid), the salicylaldehyde (from formylation of the phenol by Duff reaction), and manganese acetate, followed by anion exchange by treatment with aqueous NaCI. 

Intramolecular enantioselective arylation reactions of ketones 29 were described by Lu (Scheme 8.10) [27]. The cationic (BINAP)-palladiumhydroxo complex 30 works in combination with a basic anion-exchange resin as an additive to afford optically active cycloalkanols 31 in high yields and enantioselectivities. 

The kinetic resolution of cyanohydrins via enantioselective acylation may be converted into a dynamic process by making use of the chemical instability of cyanohydrins (Scheme 3.15) [235], Thus, racemic cyanohydrins were generated from an aldehyde and acetone cyanohydrin (as a relatively safe source of hydrogen cyanide) under catalysis by an anion exchange resin. The latter also served as catalytic base for the in-situ racemization. Enantioselective acylation using PSL and tsopropenyl acetate led to the exclusive formation of the corresponding (S)-cyanohydrin acetates in 47-91% optical purity. 

A simple one-pot dynamic kinetic resolution using recombinant Escherichia coli cells that overejqrressed ADH-A from R. ruber provided an enantioselective route to 4-alkyl-3-methyl-3,4-dihydroisocoumarins 80 as shown in Scheme 6.30. Key to the reaction was the introduction of anion exchange resin or triethylamine to promote the desired racemization of the ketone during reduction to yield en-antiopure alcohols with excellent selertivities. The reactions were performed in pH 7.5 buffer with hexane cosolvent. The reductant was supplied via isopropyl alcohol cofactor regeneration with excellent conversions [44]. 

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