Stereochemically dependant interactions

Diastereomeric salt formation results from complete proton transfer between CSA and solute. There is rapid exchange between the free acid and base and that constituting a close ion-pair. Solvation of such systems can be problematic since by its nature a salt requires a reasonably polar solvent. However, such solvents tend to dissociate the close ion-pairs to give solvent-separated ion-pairs in which the stereochemically dependent interaction responsible for induction of anisochronicity is lost. This limitation can be overcome in some cases by using mixed achiral solvents such as dg-benzene and ds-pyridine. 

These differences reflect the conformations of (+)- and meso-isomers as they sit at the air-water interface. What is much harder to elucidate is the effect of stereochemistry on intermolecular interactions. How does changing the stereochemistry at one chiral center affect interactions between diastereomers Ab initio molecular orbital calculations have been used to address the problem of separating stereochemically dependent inter- and intra-molecular interactions in diastereomeric compounds (Craig et al., 1971). For example, diastereomeric compounds such as 2,3-dicyanobutane exhibit significant energetic dependence on intramolecular configuration about their chiral centers. So far, however, little experimental attention has been focused on this problem. 

Fig. 49 Schematic representation of stereochemically dependent conformations for (+ )- and meso-C-15 9,9 ketodiacids at the air-water interface. The portion of the molecule most affecting intermolecular interactions is in brackets. Reprinted with permission from Arnett et al, 1988b. Copyright 1988 American Chemical Society.

It has been shown by Harvey et al. (1989) that incorporation of palmitic acid into a monolayer spread from stearoylserine methyl ester (SSME) breaks up intermolecular SSME interactions. The palmitic acid acts as a two-dimensional diluent. Figures 52(A-C) give the Yl/A isotherms for mixtures of FE and SE C-15 6,6 -A with palmitic acid. Dilution of the monolayer cast from the second eluting isomer with 15 mol% palmitic acid separates the diacid molecules from one another on the water surface and perhaps allows for the expression of their stereochemically dependent conformations. The mixed film (15% palmitic acid/85% C-15 6,6 -A) expands at low II and behaves in much the same manner as the single-component monolayer (C-15 6,6 -A) behaves at 30°C. Addition of 15 mole% palmitic acid into a monolayer cast from the FE C-15 diacid has little effect on its energetics of compression, indicating a stronger intermolecular interaction afforded by its stereochemically dependent conformation at the air-water interface. 

The perturber P may also function by interacting either attractively or repulsively with Rj or R2. In some cases this third interaction may cause one solvate to deviate somewhat from the conformation depicted. Stereochemically dependent third interactions allow chiral recognition not only on an NMR basis, but on an energetic basis as well (Sect. IV-E). 

Stereochemical dependences can be observed, if lone-pair or 7t-electrons are in a well-defined topological position to the carbon-hydrogenfragment133. For example, in substituted bicy-clo[2.2.1]heptanes a through-space interaction with the 7i-system leads to increased couplings134. 

The chiral recognition processes upon which the resolution of the enantiomers depends requires at least three points of interaction between the solute and the CSP, of which one must be stereochemically dependent. These points of interaction are provided by rr-donor, ir-acceptor aromatic fragments, the facility to hydrogen bond and the dipole stacking inducing structure in addition to the chiral centre within the stationary phase. 

Since enantiomers have identical physical and chemical properties, their separation requires a mechanism that recognizes the difference in their shape. A suitable mechanism for chromatography is provided by the formation of reversible transient diastereomer association complexes with a suitable chiral selector. To achieve a useful separation the association complexes must differ in stability resulting from a sterically controlled preference for the fit of one enantiomer over the other with the chiral selector. In addition, the kinetic properties of the formation/dissociation of the complex must be fast on the chromatographic time scale to minimize band broadening and achieve useful resolution. Enantioselectivity based on the formation of transient diastereomer complexes is commonly rationalized assuming a three-point interaction model [1-4,17,18]. Accordingly, enantioselectivity requires a minimum of three simultaneous interactions between the chiral selector and at least one of the enantiomers, where at least one of these interactions is stereochemically dependent. The points of interactions... 

General discussions of enantioselective recognition are given in a number of reviews.A prevalent concept is the "three-point rule. formulated by Pirkle. as Chiral recognition requires a minimum of three simultaneous interactions between the CSP(/receptor) and at least one of the enantiomers, with one of these interactions being stereochemically dependent. Schematically ... 

A useful concept for chiral separation using a transport or extraction reagent is the three-point binding rule developed for chiral chromatography. The rule states that a minimum of three simultaneous interactions between the chiral stationary phase and one of the enantiomers are necessary to achieve enantioselection, with at least one of these interactions being stereochemically dependent. We describe chiral guanidiniums that apply this rule in the recognition, extraction, or transport separation of amino acids and peptides. 

Stereochemical dependences of the vicinal fluorine-fluorine coupling have been studied by San Fabian and Westra Hoekzema by the use of MSCF in the restricted active space approach, with the SOPPA and with density functional theory the authors concluded that the through-space interaction is the main reason why /pp couplings do not follow the Karplus equation. 

Before synthetic chiral stationary phases were developed, attempts were made to use naturally occurring chiral materials for the stationary phase. Quartz, wool, lactose and starch were inadequate but triacetylated cellulose has met with some success. The synthetic stationary phases introduced by Pirkle are able to interact with solute enantiomers in three ways, one of which is stereochemically dependent. Typically these interactions are based on hydrogen bonding, charge transfer (rc-donoi -acceptor based) and steric repulsive types. An independent chiral stationary phase therefore consists of chiral molecules each with three sites of interaction bound to a silica (or other) support. Early work in this area demonstrated that 5-arginine bound to Sephadex would resolve 3,4-dihydroxy-phenylalanine, and that direct resolution of chiral helicenes could be accomplished with columns packed with 2-(2,4,5,7-tetranitro-9-fluorenylideneaminoxy)-propionamide or tri-P-naphthol-diphosphate amide. Amino acid esters have also been resolved with a silica bound chiral binaphthyl crown ether, but better separations are achieved with A-acylated amino acid derivatives with amino-acid derived chiral stationary phases. 

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