Differentiation diastereoisomer

As already mentioned, we chose three different physicochemical properties for studying the influence of the surface area and fractal dimension in the ability of dendritic macromolecules to interact with neighboring solvent molecules. These properties are (a) the differential chromatographic retention of the diastereoisom-ers of 5 (G = 1) and 6 (G = 1), (b) the dependence on the nature of solvents of the equilibrium constant between the two diastereoisomers of 5 (G = 1), and (c) the tumbling process occurring in solution of the two isomers of 5 (G = 1), as observed by electron spin resonance (ESR) spectroscopy. The most relevant results and conclusions obtained with these three different studies are summarized as follows. 

Both techniques can be applied in two ways. In the first method the enantiomeric mixture (or racemate) is converted into a diastereoisomeric mixture with a suitable optically pure reagent, and this mixture chromatographed on a column having an achiral stationary phase. Separation then depends on the differential molecular interactions of the diastereoisomers with the stationary phase. In the second method, the stationary phase on the support material (usually chemically bonded) contains a chiral, optically pure residue. In this case the mixture of enantiomers which is loaded directly on to the column is separated by virtue of differential diastereoisomeric molecular interactions between each enantiomer and the optically pure stationary phase. 

Of interest from the mechanistic point of view is the formation of only one diastereoisomer in the methylation step VII/119 — VII/124. Two possible explanations are discussed in the literature [3]. First, a stereoselective methylation of the aldehyde group takes place under the influence of the nitro group leading to the correct stereochemistry in VII/124. The second possibility involves the titanium reagent. An equilibrium can exist between the diastereoisomeric mixture VII/121 and the pure VII/123 via the isomer VII/122. By quenching the equilibrium mixture, only the thermodynamically most stable isomer would be obtained [3]. A differentiation of the two mechanisms seems possible using chiral reaction conditions. Treatment of the chiral (-)-VII/119 (50 % ee), prepared by an asymmetric Michael addition of acrylaldehyde and 2-nitrocyclohexa-none in the presence of cinchonine [84], with achiral dimethyltitaniumdiisopro-poxide yields only achiral methylation products. This experiment shows that no stereoselective methylation takes place. The second consideration, then seems to be more likely (Scheme VII/24)7). 

With the development of theories of chemical structure and the science of stereochemistry, greater sophistication became possible. As already noted, Fischer used enzymes in 1894 which differentiated between carbohydrate diastereoisomers. By about the turn of the nineteenth century, the role of three-dimensional structures began to emerge. For example, in a chapter entitled The Relations of Stereochem-... 

Since the two products or complexes are diastereoisomers they have different physical properties and Cushny attributed the different pharmacological properties to the different physical properties. However, he seemed to ignore the overall three-dimensional structure, and Parascandola suggests that Cushny had difficulty in imagining that a receptor could actually differentiate between enantiomeric structures [24]. 

The compound /3-phenylglutaric anhydride, 49, contains enantiotopic ligands. On reaction with ( —)-a-phenylethylamine the two diastereoisomers of the monoamide, 50 and 51, were formed in unequal amounts [67]. In contrast to the earlier statement (the products are usually enantiomers in an enantiodifferentiating process), the products here are diastereoisomers. Of course, if the amine component of the amide were to be removed, the products from the substrate anhydride would be enantiomers. This differentiation between enantiotopic groups was important in the early days of the citrate story. It proved the possibility of differentiation in homogeneous solution, presumably without a three-point attachment. 

The stereoselectivity of the allylic hydroperoxidation also depends on se eral factors. With chiral allylic alcohols or allylic amines 200, a hydrogen is developed between ]02 and the vicinal hydroxyl or amino group. The fac differentiation results from an approach of 102 in the transition state that mi mizes 1,3-allylic strain. 201 and 202 can be obtained with a diastereoisome excess higher than 90% in CCI4. As previously indicated for the formation dioxetanes and 1,4-endoperoxides, the selectivity decreases considerably in presence of hydroxylic solvents [123]. When hydrogen bonding is no more pos ble in 203, the stereofacial differentiation is steered by steric and electronic rep sion effects at the level of the possible diastereoisomeric transition states 204 is formed selectively (Scheme 54). 

Inspection of Eqs. (1) and (2) reveals that both effects accumulate for one of the two diastereoisomers while they attenuate each other for the second. The direction and the magnitude of the SE bear information about the steric requirements of the rate-determining step. Note that a differentiation of the KIEs associated with the transfer of the diastereotopic H(D) atoms is not required in Eqs. (1) and (2) because any difference between these KIEs would itself represent a steric effect and is thus already included in the parameter SE. Further, only one of the two stereocenters is actively involved in the bond cleavage, while the second, i.e., the methyl group at C(3), just serves as a spectator. As a consequence, both diastereoisomers lead to the same products. This distinction is quite important in comparison to systems in which the activation of both stereocenters in a diastereoisomer takes place (see below). 

H-nmr spectroscopy readily enables the differentiation of chiral from achiral (meso) diastereoisomers of 3,5- and 2,6-dimethyl-4-phenylpiperidines because in the meso forms the two methyls have identical environments and give rise to the same resonance, while chiral isomers involve an axial-equatorial pair that results in two separate methyl signals (see 39). The configurations of both the chiral 2,6- and 3,5-dimethyl reversed ester analogs of pethidine have been confirmed by X-ray crystallography/27 41)... 

The fust use of an asymmetric Diels-Alder reaction in enantioselective synthesis, reported by Corey and Ensley (1975), involved both diene and dienophile face differentiations (Scheme 74). Addition of 5-(methoxymethyl)cyclopentadiene (304) to acrylic acid (305a) proceeded endo selectively and anti with respect to the diene substituent. Consequently, the relative configuration of the four new chiral centers in (30fo) was determined and, of four possible diastereoisomers, one was formed selectively. As expected, the diene added at the same rate to the two enantiotopic dienophile ir-faces, affording a 1 1 mixture of the enantiomers (lf )-(306a) and (15)-(306a). 

Since the (4R,6R) tetramer and (4S,6S) tetramer are enantiomers, they are not separated by conventional chromatographic columns. The same is true for the (4S,6R) and (4R,6S) stereoisomers. Based on the formation of these stereoisomers, analytical pyrolysis of polypropylene is able to differentiate between isotactic and syndiotactic polymers. One fragment molecule that can be used for this purpose is the tetramer. However, other fragments from the two polymers also are diastereoisomers and, for this reason, the pyrograms of isotactic and syndiotactic polypropylene show differences. 

For the differentiation between an isotactic polystyrene and the syndiotactic material, it is necessary to investigate the tetramer (or higher) fragments present in a pyrogram, in the same manner as it was shown for polypropylene. The tetramer fragments from isotactic polystyrene and syndiotactic polystyrene are diastereoisomers and can be separated by GC on a nonchiral column [45]. The two chiral centers are in this case (R,R) and (S,R) as shown in the following formulas ... 

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