Stereochemical studies using chiral acetates

The reaction sequence shown in Scheme 21 provides a tool for determining the stereochemistry of addition of a number of nucleophiles. One initial study provided some surprises. In the chloride-free as well as the chloride-containing system in acetic acid, previous kinetic studies had suggested anti addition. However, stereochemical smdies using chiral 22a as reactant indicated syn addition in both systems. Furthermore, the addition of LiCl to the chloride-containing system completely reversed the addition to anti. These two reactions require further study. 

A method for the determination of carbon-linked methyl groups (and, by extension, used in the analysis of chiral methyl groups in stereochemical studies of enzyme-catalyzed reactions acting on methyl groups). In this procedure, the methyl groups are converted to acetic acid by oxidation of the metabolite with chromic and sulfuric acids. Milder versions are also available. 

Since these early studies, numerous additional procedures have been developed for the synthesis of chiral labeled acetic acid and other chiral labeled molecules by chemical (I41-15I) and enzymic methods 152-155). The malate synthase/fumarase system described above continues to be the most widely used method for the stereochemical analysis of chiral labeled acetic acid resulting from the degradation of product molecules containing chiral methyl groups. 

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

The same authors used DDCV in combination with the co-surfactants 1-butanol, 1-pentanol, 2-pentanol, 1-hexanol, 2-hexanol, cyclopentanol, and cyclohexanol for the analysis of N-methyl ephedrine, atenolol, metoprolol, ephedrine, pseudoephedrine, and synephrine. Ethyl acetate was applied as the microemulsion oil core, and as BGE, a 50-mM phosphate buffer with pH 7.0 was used. Cyclopentanol yielded the best enantioselectivity for three out of six compounds, 1-butanol for two, and 2-pentanol for one analyte. The most limited enantioselectivities for all compounds were observed with 1-pentanol and 1-hexanol. In a subsequent study," the simultaneous use of a chiral surfactant and chiral oil for MEEKC is discussed. Six combinations of DDVC (R, S, or racemic, 2.00% w/v), co-surfactant racemic 2-hexanol (1.65% v/v), and chiral oil dibutyl tartrate (d, L,or racemic, 1.23% v/v) were examined for the separation of the compounds mentioned above. Dual-chiral-ity microemulsions (emulsions in which the surfactant and oil are in opposite stereochemical configurations) provided both the largest and smallest enantioselectivities, as a result of small positive and negative synergies between the chiral microemulsion components. / -DDVC, 2-hexanol, and 5-dibutyl tartrate provided the highest enantioselectivity for all compounds except for metoprolol. 5-DDVC, 2-hexanol, and 5-dibutyl tartrate ranked lowest for all three ephedrine derivatives, while 5-DDVC, 2-hexanol, and R-dibutyl tartrate gave the lowest values for metoprolol and synephrine. 

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