Absolute configuration solvent effects

Similar additions may be performed with the enamine 13. However, with 3-buten-2-one or methyl 2-propenoate Lewis acid catalysis is needed to activate the Michael acceptor chloro-trimethylsilane proved to be best suited for this purpose. A remarkable solvent effect is seen in these reactions. A change from THF to HMPA/toluene (1 1) results in a reversal of the absolute configuration of the product 14, presumably due to a ligand effect of HMPA235. 

Another problem that required solving was the moderate yield obtained in the cyclopropanation reaction when only one equivalent of styrene was used. By increasing the amount of styrene up to its use as the reaction solvent, a noticeable effect on the selectivities was observed when laponite was used as the support [58]. The active role of the clay support was definitely estabhshed when the results in homogeneous and heterogeneous phases were compared (Table 9). These effects involved the reversal of the trans preference in solution to the cis preference with the laponite-supported catalyst in styrene, and also a reversal in the absolute configuration of the major cis enantiomer ob-... 

As mentioned in the introduction, the first empirical correlation between the absolute configuration of dopants and the handedness of induced cholesterics was proposed in 1975.20 The first attempt to find a general correlation was a few years later Krabbe et al.58 related the sense of the cholesteric to a stereochemical descriptor of the dopant based on the effective volume of the substituents and listed many compounds following this rule. However, exceptions were described at that time,59 and, furthermore, this approach neglects the role of the structure of the nematic solvent in determining the sense of the cholesteric. It is well known that chiral compounds may induce cholesterics of opposite handedness in different nematics.60,61... 

Recent experimental and theoretical studies on crystal growth, especially in the presence of tailor-made inhibitors, provide a link between macroscopic and microscopic chirality. We shall discuss these principles in some detail for chiral molecules. Furthermore, we shall examine whether it is indeed feasible today to establish the absolute configuration of a chiral crystal from an analysis of solvent-surface interactions. Since these analyses are based on understanding the interactions between a growing crystal and inhibitors present in solution, we shall first illustrate the general mechanism of this effect in various chiral and nonchiral systems. 

In this context, it should be pointed out that the correlation between aromatic solvent-induced shifts (ASIS) and the axial or equatorial orientation of protons in cyclic sulfoxides and sulfites is quite distinct (211-213) and may be utilized in the assignment of configurations. For instance, the absolute configuration at sulfur was assigned to the penicillin sulfoxide 202 based on analysis of the effect of aromatic solvents on the chemical shifts of protons of the thiazolidine ring (214,215). 

It must be stressed, however, that the methyl alkyl sulfoxide rule is not valid for alkyl benzyl and alkyl allyl sulfoxides (222-224), where the electronic, steric, and solvent effects exert influences on the chiroptical phenomena in a way that is difficult to rationalize. This rule was found to be satisfactory and was used for the assignment of absolute configurations of steroidal (200,201,225), penicillin (226), and amino acid (227-230) sulfoxides. 

FIGURE 6. 500 MHz H-NMR partial spectra of 2-butylzinc bromide in the presence of 1 equivalent of (- -)-45, or its racemic counterpart ( )-45, at different temperatures. The side-product butane is represented by H. Methylene protons (c) are not shown in spectmm (a) due to solvent peak overlap. Assignments of the absolute configurations were made based on predicted anisotropic effects and are represented in spectrum (b). Reproduced by permission of Wiley-VCH from Reference 99... 

A racemic mixture of three-layered [3.3]paracyclophane (45) was resolved into two enantiomers by chiral HPLC (on a Daicel OD column), and their absolute configuration was determined by a comparison of the experimental CD spectrum with the theoretical one at the TD-DFT-B3-LYP/TZVP level [55]. A simple model, composed of two p-xylenes and durene (the side chains were modeled again by methyl groups), was used to explain the origin of the chiroptical properties of the three-layered cyclophane system. Due to the flexibility of the [3.3]paracyclophanes, the solvent effects on the conformer distribution and thus on the chiroptical properties were significant (Fig. 10). 

Geselowitz et al. (200) showed that the oxidation of A,A-[Co(en)3] by A[Co(edta) ]" results in the production of A[Co(en)3] in excess of the other enantiomer, and vice versa for A[Co(edta)] . The enantiomeric excess was around 9% in H2O but rose with decreasing solvent polarity to 40% in sulfolane. The substitution of the en backbone of edta with alkyl groups has a negligible effect on the enantiomeric excess of [Co-(enlal or on the rate of the reaction. This seems to be evidence for the view that the selectivity arises from the pre-equilibrium step of the reaction and that [Co(edta)] and analogues were oriented with a carboxylate face toward the [Co(en)3] ion. The same conclusion was reached (221) in the study of the ion pair formation between [Co(edta) ] and [Co(en)3] + that is, that the stronger ion pairs were formed between complexes of opposite absolute configuration and that [Co-(edta) ] associated via its pseudo-C3 carboxylate face. 

The formal [3+3] cycloaddition of vinylogous amide 172 was effected with chiral amine salts to provide 173 enantioselectively (Scheme 49). These reactions were studied with respect to solvent, counterion, and temperature effects, and the probable mechanism and absolute configuration of the products were determined <05JOC4248>. 

Since the formation of a chiral lithium alkoxide is likely to be involved in the asymmetric addition process, various ratios of the components (chiral ligand -BuLi 5a) were examined. The results of this study revealed a remarkable solvent effect on both efficiency and selectivity for -BuLi additions, and a dependence of the absolute configuration of the amine 6 on the solvent employed. The amino alcohols such as 7 and 8 gave only poor enantioselectivities in the butyl addition... 

Manumycin A (52) was the first metabolite isolated from Streptomyces parvulus (strain Tii 64) [110] and its structure and absolute configuration have been described [111]. Other minor components such as manumycin B (53), C (54) and D (55) have similar structural moieties indicating their close structural and biosynthetic relationship [112]. These other compounds differ in the polyketide assembly of the acylamino side chain and in the stereochemistry at C-4. Manumycin D (55) is the first of the manumycin type compounds without an oxirane ring in the mC7N unit. Their structural elucidation has been recently carried out [112] by H NMR spectroscopy using aromatic solvent induced shift (ASIS) effects at the olefinic 3-H and circular dichroism (CD) spectroscopy has been used to determine the absolute stereochemistry of the mC7N unit. 

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