Diastereomer discrimination

We refer to any measurable difference between diastereomeric pairs as a diastereomer discrimination. We use the term chiral discrimination to include both enantiomer and diastereomer discrimination for the general case. 

The ability of a chiral molecule to distinguish between the enantiomers of a second (different) chiral molecule was defined in Sect. II as a diastereomer discrimination. This phenomenon may be observed in a mixed monolayer of two chiral surfactants and may also occur when a chiral substance is dissolved in the aqueous subphase under the monolayer of a second chiral substance. As before, examples of such chiral discrimination would not include those whose difference in monolayer behavior results only from the gross structural differences of diastereomers such as the different force-area characteristics exhibited by mixed monolayers of l-oleoyl-2-stearoyl-3-s -phospha-tidylcholine with epimeric steroids (120). The relevant experiment, that of comparing the monolayer behavior of mixed monolayers of cholesterol with enantiomeric phospholipids, has been reported (121). As might be anticipated from our previous discussion of... 

The relevance of such a diastereomer discrimination to the transport of chiral molecules, such as pharmaceuticals or biochemicals, through hydrophobic barriers, such as cell membranes, is obvious. Furthermore, since poly(DL-lysine) followed the same general pattern of behavior displayed by the other three samples, the observed surface-pressure changes probably were not due to helicalization of the polypeptide. Whereas poly(L-lysine) and poly(D-lysine) form helices with opposite screw sense, the random copolymer poly(DL-lysine) is to a large extent prevented from forming helices. 

Because this area is not too well known, the authors have taken pains to describe, in some detail, experimental monolayer chemistry. The centerpiece of the chapter is enantiomer and diastereomer discrimination in monolayers. It concludes with a discussion of surface properties, in particular energetics, which are quite sensitive to stereochemistry. We call attention to the fact that this chapter is of potential interest to biochemists, notably those concerned with lipids and with cell membrane organization. 

When enzymes like alcohol dehydrogenase, are chiral, reduce carbonyl groups using coenzyme NADH, they discriminate between the two faces of the trigonal planar carbonyl substrate, such that a predominance of one of the two possible stereoisomeric forms of the tetrahedral product results, i) If the original reactant was chiral, the formation of the new stereocenter may result in preferential formation of one diastereomer of the product => a diastereoselectiv reaction. 

In the kinetic resolution, the yield of desired optically active product cannot exceed 50% based on the racemic substrate, even if the chiral-discriminating ability of the chiral catalyst is extremely high. In order to obtain one diastereomer selectively, the conversion must be suppressed to less than 50%, while in order to obtain one enantiomer of the starting material selectively, a higher than 50% conversion is required. If the stereogenic center is labile in the racemic substrate, one can convert the substrate completely to gain almost 100% yield of the diastereomer formation by utilizing dynamic stereomutation. 

The success of bis(oxazoline)-copper(II) catalyzed Diels-Alder reactions involving acryloylimides as dienophiles has been extended to the Michael reaction, Eqs. 204 and 205. The observed enantiofacial discrimination in the Diels-Alder reactions was expected to translate well to Michael reactions involving enolsilanes as nucleophiles. Indeed, fumarate-derived imides afford Michael adducts of enolsilanes in high enantioselectivity (240). Diastereoselectivity in these reactions may be regulated by judicious choice of thioester and enolsilane geometry to provide either diastereomer in high selectivity (>99 1 syn or 95 5 anti). 

There are two possible approaches for the preparation of optically active products by chemical transformation of optically inactive starting materials kinetic resolution and asymmetric synthesis [44,87], For both types of reactions there is one principle in order to make an optically active compound we need another optically active compound. A kinetic resolution depends on the fact that two enantiomers of a racemate react at different rates with a chiral reagent or catalyst. Accordingly, an asymmetric synthesis involves the creation of an asymmetric center that occurs by chiral discrimination of equivalent groups in an achiral starting material. This can be done either by enan-tioselective (which involves the reaction of a prochiral molecule with a chiral substance) or diastereoselective (which involves the preferential formation of a single diastereomer by the creation of a new asymmetric center in a chiral molecule) synthesis. 

One may use the stronger term chirality discrimination when a substantial suppression of one intermolecular diastereomer with respect to the other occurs. This requires multiple strong interactions between the two molecular units and therefore more than simple monofunctional alcohols. Some examples where one of the molecules involved is a chiral alkanol are reported in Refs. 112 and 119 121. Pronounced cases of higher-order chirality discrimination have been observed in clusters of hydroxy esters such as methyl lactate tetramers [122] and in protonated serine octamers [15,123,124]. The presence of an alcohol functionality appears to be favorable for accentuated chirality discrimination phenomena even in these complex systems [113,123,125,126]. Because the border between chirality recognition and discrimination is quite undefined, it is suggested that the two may be used synonymously whenever both molecular partners are permanently chiral [127]. 

These results may be compared with those of the experiments of Schwartz and Carter (64) and Cohen (65a) with fl-phenylglutaric anhydride. [See also the more recent results of Fujita and co-workers with meso-2,4-dimethylglutaric acid (65b).] The former group showed that a chiral amine could discriminate between attack at the pro-(/J) and pro-(S) carbonyl groups of the anhydride. The two diastereomers were formed in a ratio of 3 2, with optical purities of about 20%. 

Discrimination of the racemic aluminum reagent 4 can be carried out using chiral ketone 5, which deactivates one enantiomer of racemic 4. The hetero-Diels-Alder reaction is then catalyzed by the remaining opposite enantiomer of racemic 4 (Scheme 8.4). The combination of racemic 4 and chiral ketone 5 in a 1 1 ratio gives better enantiomeric excess than in a 2 1 ratio, implying that one diastereomer of the 4/5 complex readily dissociates to yield optically pure 4 and the chiral ketone 5. 

Achiral A,A-diisopropyl-ferrocenecarboxamide (440) was deprotonated by Snieckus and coworkers by n-BuLi/(—)-sparteine (11) (equation 119) . The base discriminates well between the enantiotopic protons H(2) and H(5) in the substituted ring to form the diastereomer 441 with high selectivity. Trapping the intermediate with a couple of different electrophiles afforded the substitution products 442a-d with 85 to 99%... 

Other nitrones (21-23) having the chiral moiety located at the carbon atom have been applied in reactions with various alkenes (Scheme 12.10) (33-35). Nitrone 21 offered poor discrimination in 1,3-dipolar cycloadditions with benzyl crotonate, as all four diastereomers were obtained in both reactions (33). The fluorinated nitrone... 

If the diastereomer can largely be discriminated by the adsorbent, one speaks of high diastereoselectivity . As mentioned previously, in order to generate a pronounced effect, certain molecular-structure requirements have to be fulfilled ... 

Treatment of the /J-hydroxy complex 15 with two equivalents of strong base followed by alkylation produces a mixture of the diastereomers 20 and 21 with an anomalously low d.r.27. The low degree of diastereofacial discrimination has been rationalized by invoking the formation of both rotamers of the initially formed alkoxide, 16 and 17. Rotamer 16 undergoes a-proton abstraction by a second equivalent of base to form the chelated dianionic Tf-enolate 18 which upon alkylation affords the usual diastereomer 20. Rotamer 17 is thought to rapidly transform to a metallo-lactone species by intramolecular attack of the alkoxide upon the proximate carbon monoxide ligand, which must occur faster than conversion to the less sterically encumbered conformer 16. Subsequent deprotonation to generate dianion 19, which is constrained to exist as the unusual Z-enolate, followed by alkylation provides the other diastereomer 21, which is formed in an amount nearly equal to 20. 

More complicated results are observed in the reaction of 4,4-dimethyl-l,6-heptadiyn-3-ol 269 with Bu Me2SiH, giving a mtKture of 270 and 271 (Equation (44)). Discrimination of the two acetylenic moieties in 269 is hard at the silylrhodation, and thus a complex mixture of regioisomers and diastereomers results. In any event, use of rhodium species as a catalyst is essential for smooth construction of bicyclo[3.3.0]-octenone frameworks. 

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