Chiral counterion

Figure 5.45 Cationic gemini amphiphiles having chiral counterions. TEM images of representative twisted ribbons formed by 16-2-16 tartrate (49 + 50) at 0.1% in water for various values of enantiomeric excess (a) 0 (racemate) (b) 0.5 (c) 1 (pure L) (d) 1 (pure L) in presence of 1 eq sodium L-tartrate. Bar = 100 nm. Reprinted with permission from Ref. 165. Copyright 1999 by Macmillan Magazines.

The separation mechanism is based on stereoselective ion-pair formation of oppositely charged cationic selector and anionic solutes, which leads to a difference of net migration velocities of the both enantiomers in the electric field. Thus, the basic cinchona alkaloid derivative is added as chiral counterion to the BGE. Under the chosen acidic conditions of the BGE, the positively charged counterion associates with the acidic chiral analytes usually with 1 1 stoichiometry to form electrically neutral ion-pairs, which do not show self-electrophoretic mobility but... 

The analysis of these 25 compounds confirms the flexibility of dpg/dpg+. It can adopt a propeller like conformation and induce the formation of chiral crystals. It establishes predominantly two-dimensional H-bonding networks with the counter ion. From the perspective of the crystal engineer, an anticlinal conformation would maximize the non-linear properties of the molecule. However the non-linear optical response depends greatly on the molecular alignment. Non-centrosymmetric dispositions have not yet been achieved for dpg with an anti-anti conformation. The best strategy to attain NLO samples is by inducing a syn-anti conformation where a propeller structure might induce a chiral disposition of molecules and thus a non-centrosymmetric order. Another successful approach is to force crystallization with a chiral counterion. 

The logical extension of the ion-pair chromatographic technique, using chiral counterions as CMPAs has been impressively applied, for the first time, to the resolution of chiral amino alcohols (betablockers) by Pettersson and co-workers142. 

Steuer et al. demonstrated the use of supercritical fluid chromatography in the separation of enantiomers of 1,2 amino alcohols, namely pindolol, metoprolol, oxprenolol, propranolol, and DPT 201-106 using ionpairing modifiers [21]. The mobile phase consisted of carbon dioxide mixed with acetonitrile containing triethylamine as a counterion and /V-benzo-xycarbonylglycyl-L-proline as a chiral counterion. They found that the ca-... 

Diastereomeric complexes can also be formed by ion-pairing of an enantiomer with a chiral counterion. In order to form this diastereomeric complex, it has been postulated that at least three interaction points between the ion pair are required [250]. Nearly all of these form weak complexes in aqueous mobile phases. Consequently, the chromatographic methods that have been developed have been either silica or diol columns with low-polarity mobile phases. Enantiomeric amines, such as the beta-blockers, have been optically resolved when (-l-)-lO-camphorsulfonic acid was used as the chiral counterion [251]. Enantiomers of norephedrine, ephedrine, pseudoephedrine, and phenyramidol have all been resolved from their respective enantiomers with n-dibutyltartrate [252]. Enantiomers of naproxen, a chiral carboxylic acid, are resolved from each other by either using quinidine or quinine in the mobile phase [253]. In these studies, silica... 

Oda et al. described the use of gemini surfactant/tartaric acid admixtures which could trap up to 1200 solvent molecules per molecule of the gelator [72]. In these gelators, the biscationic geminis contain chiral counterions and they associate to form gels with both water and organic solvents such as chloroform... 

Enantioselective versions of this reaction have been recently developed with achiral substrates. Two different strategies have been applied to obtain an effective chiral catalyst for that purpose the usual chiral phosphine ligand (equation 102) and the novel employment of a chiral counterion of the metal catalyst as the source of chirahty (equation 103). ... 

The enantioselective hydroaminations of allenes with chiral phosphine catalysts was accomplished with substrates that had a terminal symmetric substitution and with the amines protected as carbamates or sulfonamides. The same symmetric substituents were necessary for the enantioselective transformation nsing chiral counterions. However, very recently, high enantiomeric excesses were reached with trisubstituted asymmetric allenes by a dynamic kinetic enantioselective hydroamination of allenyl carbamates (eqnation 110), even thongh the E/Z ratio of the prodncts was not optimal. 

Separation of chiral isomers requires chiral counterions. Cations are frequently resolved by using the anions z -tartrate, antimony d-tartrate, and a-bromocamphor-iT -sulfonate anionic complexes are resolved by the bases brucine or strychnine or by using resolved cationic complexes such as [Rh(en)3] " . In the case of compounds that racemize at appreciable rates, adding a chiral counterion may shift the equilibrium even if it does not precipitate one form. Apparently, interactions between the ions in solution are sufficient to stabilize one form over the other. 

While this manuscript was in preparation, the first example of twisting of the bilayers of cationic gemini surfactants by chiral counterions like tartrate, glucarate, malate, and gluconate was reported. ... 

Ion-pair formation with a chiral counterion has also been used to separate enantiomers. Thus, separation of enantiomeric amines has been achieved by ion-... 

Unlike enantiomers, diastereomers have different solubilities in an achiral environment. Many chiral counterions, such as arginine and lysine, are commonly used to prepare salts of an ionic drug in order to improve its pharmaceutically relevant properties. However, when the drug is chiral, a chiral counterion should be used with caution. If the drug or the counterion is racemic, diastereomeric salts will be formed, constituting a heterogeneous system. Because the solubilities of diastereomers differ, a diastereomeric mixture of chiral salts is undesirable in a formulation. 

Higher levels of chiral induction were achieved with (/ )-xylyl-BINAP(Au-/i-nitrobenzoate)2 or (/ )-ClMeOBIPHEP(Au-p-nitrobenzoate)2 as catalyst (Scheme 4-63). These allow the smooth formation of chiral pyrrolidines or piperidines with up to 99% ee and high chemical yield from the corresponding trisubstituted tosyl-protected y- or 5-aminoallene. Gold catalysts with a chiral counterion can also be employed for the highly enantioselective intramolecular exo-hydroamination of aminoallenes. ... 

Instead of using Br0nsted bases, chiral Br0nsted acids can also be utilized to enanti-oselectively acquire Mannich products. The acidic catalyst assists in the Mannich reaction by protonating the imine, thereby forming an iminium ion to which the deprotonated Brpnsted acid catalyst coordinates. This chiral counterion directs the incoming nucleophile and leads to an optically active Mannich product. 

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