Achiral separation mechanisms

Enantiomers are derivatized with an optically pure chiral derivatization reagent to form a pair of diastereomers. The ability to resolve the diastereomeric derivatives on an achiral sorbent is enhanced when the chiral centers of the enantiomers and the derivatives are in close proximity [181]. Two different separation mechanisms have been proposed. One postulates that the diastereomers are separated by differences in molecular structure and polarity [182], The other possible mechanism is based on differences in the diastereomer energies of adsorption [183]. Table 5.7 lists the chiral reagents that have been used for separation of enantiomers as diastereomers. 

Many of the modes of CEC illustrated in Table 3.1 are applicable to both gradient and isocratic elution, aqueous and non-aqueous conditions, as well as to chiral and achiral separations and these will be discussed within the appropriate sections. The complex mechanisms responsible for selectivity will not be discussed, rather this chapter will be limited to describing the scope for application of the different CEC modes. 

The achiral salt, N-(2-hydroxyethyl)-N,N,N-trimethylammonium chloride (111) was found to form a mixture of two 1 1 inclusion complexes lOb-111 and lOc-111 as conglomerate crystals, but not the racemic complex lOa-111. The result strongly suggests that enantiomeric separahon of 10a can easily be done by complexahon with 111. lOb-111 and lOc-111 crystals can easily be separated mechanically. By re-peahng the seeding experiments as shown in Scheme 3.3-3,10b of 99% ee and 10c of 99.5% ee were finally obtained in 66 and 64% yields, respechvely [49]. 

We can safely assume that the receptor site is chiral. It is also clear that there cannot be separate receptor sites for each and every odorous substance. Therefore, many receptor sites must be able to react with many, but not all, substances. A receptor site can distinguish both between a pair of enantiomers and between closely related achiral molecules, but it seems unreasonable to assume that there be two separate mechanisms for the chemorecognition of chiral and achiral molecules. 

The separation can be based on one or more of three possible mechanisms as follows (1) The two enantiomers of a solute have a tendency to form complexes with the selector in the mobile phase to different extents. The diastereomeric complexes formed and the free enantiomers have a different distribution to the achiral stationary phase. (2) The diastereomeric complexes formed have a different distribution to the achiral stationary phase. (3) The chiral selector adsorbs to the achiral stationary phase to form a chiral pseudostationary phase [49]. 

An unexpected but possibly related phenomenon is the separation of enantiomers of nicotine in a totally achiral system [256]. The mechanism is unclear but may involve the formation of in situ diastereometric dimers, where a dimer formed from the same two enantiomers could possibly resolve from a racemic dimer. 

The resolution of racemic compounds through the formation of reversible diastereomer complexes is certainly an example of the generation of chirality upon association of an achiral solute (the racemate to be resolved) and a chiral solute (the resolving agent). Such interactions are normally considered solely from the separations point of view [11], and only rarely is CD used to follow the association mechanism. It is evident, however, that the spectroscopic method would be of great value to characterize the associated species. 

Maleic anhydride reacts with cyclopenta-1,3-diene in a Diels-Alder reaction. Since there is a plane of symmetry, the reaction can lead to two achiral compounds, which are diastereomers of each other, containing an endo- or exo-oriented dicarboxylic anhydride group. These differ in absolute and relative configuration at the bond shared by both rings. Under normal conditions the Diels-Alder reaction proceeds stereospecifically to yield preferentially the endo product. Note that in the tricyclic product no trans fusion in the ring system is possible as a consequence of the reaction mechanism. Subsequent reduction of the products therefore affords two diols, which are also diastereomers of each other. These may be separated by chromatography on an achiral stationary phase. 

Chiral polymers have been applied in many areas of research, including chiral separation of organic molecules, asymmetric induction in organic synthesis, and wave guiding in non-linear optics [ 146,147]. Two distinct classes of polymers represent these optically active materials those with induced chirality based on the catalyst and polymerization mechanism and those produced from chiral monomers. Achiral monomers like propylene have been polymerized stereoselectively using chiral initiators or catalysts yielding isotactic, helical polymers [148-150]. On the other hand, polymerization of chiral monomers such as diepoxides, dimethacrylates, diisocyanides, and vinyl ethers yields chiral polymers by incorporation of chirality into the main chain of the polymer or as a pedant side group [151-155]. A number of chiral metathesis catalysts have been made, and they have proven useful in asymmetric ROM as well as in stereospecific polymerization of norbornene and norbornadiene [ 156-159]. This section of the review will focus on the ADMET polymerization of chiral monomers as a method of chiral polymer synthesis. 

These phases have been prepared by polymerization of N, N -diaUyl derivatives of tartardiantide and grafted onto silica gel. As these phases are crosslinked and bonded to sihca gel, they are insoluble in organic solvents and there is no limitation regarding the choice of mobile phase. Normal mode, reversed-phase and supercritical fluid conditions have been applied. They show good mechanical stability, but the relatively high content of achiral sihca gel in these CSPs reduces their loading capacity. A few preparative separations have been reported on these two CSPs (Kromasil) [52-54], but so far they have not been widely used for preparative apphcations. 

For achiral molecules that, when coupling with a chiral molecule (mostly alkaloids, such as brucine, cinchonidine, and sparteine), form a pair of diastereomers with different physical properties that can be separated by the methods of fractional crystallization, column chromatography, etc., resulting in the enantiomeric resolution. No actual mechanism is necessary for this reaction. 

The above-mentioned chemical catalytic routes lead to racemic AHA mixtures. For the direct use of LA (or its esters) as a solvent or platform molecule for achiral molecules like acrylic acid and pyruvic acid, stereochemistry does not matter. The properties of the polyester PLA, the major application of LA, however, suffer tremendously if d and l isomers are built in irregularly [28]. This is exemplified by atactic PLA, made from racemic LA, which is an amorphous polymer with low performance and limited application. However, when l- and D-lactic acid are processed separately into their respective isotactic L- and d-PLA, as discovered by Tsuji et al., a stereocomplex is formed upon blending these polymers. This polymer exhibits enhanced mechanical and thermal properties [28, 164]. A productive route to D-Iactic acid is, however, missing today. If the chemocatalytic routes to LA are to become viable, enantiomer resolution of the racemate needs to be performed. Given separation success, a cheap source of o-lactic acid will be unlocked immediately, providing an additional advantage over the fermentation route (cfr. Table 2). 

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