Stereochemical differentiation

A. Kaunzinger, P. Podebrad, R Liske, B. Maas, A. Dietiich and A. Mosandl, Stereochemical differentiation and simultaneous analysis of 3-,4- and 5-hydroxyalkanoic... 

It is not surprising, therefore, that this dynamic technique was chosen to provide information on chiral interactions in compressed films. Given that these stereochemically differentiated systems may have dramatically different HI A isotherm characteristics, and hence different packing arrangements, it is plausible that their flow properties are stereochemically differentiated as well. 

Ai-Stearoylamino acids and their methyl esters were synthesized from enantiomeric and racemic forms of tyrosine, serine, alanine, and tryptophan (Fig. 16). Analogs of these molecules were investigated initially over 30 years ago by Zeelen and Havinga, who found stereochemical differentiation in the monolayer HjA isotherms of these materials (Zeelen, 1956 Zeelen and Havinga, 1958). We have extended this study using more sensitive Langmuir balances, a wider array of dynamic and equilibrium techniques, and the A-stearoyl methyl esters of the amino acids (Harvey et al., 1989 Harvey and Arnett, 1989). 

Figure 17 shows the 11/A isotherms of racemic and enantiomeric films of the methyl esters of 7V-stearoyl-serine, -alanine, -tryptophan, and -tyrosine on clean water at 25°C. Although there appears to be little difference between the racemic and enantiomeric forms of the alanine surfactants, the N-stearoyl-tyrosine, -serine, and -tryptophan surfactants show clear enantiomeric discrimination in their WjA curves. This chiral molecular recognition is first evidenced in the lift-off areas of the curves for the racemic versus enantiomeric forms of the films (Table 2). As discussed previously, the lift-off area is the average molecular area at which a surface pressure above 0.1 dyn cm -1 is first registered. The packing order differences in these films, and hence their stereochemical differentiation, are apparently maintained throughout the compression/expansion cycles. 

Unlike the catalytic epoxidation or aziridination reactions of simple alkenes, where enantiocontrol is the only stereochemical differentiation, synthetically effective intermolecular cyclopropanation requires both diastereocontrol and enantiocontrol. High diastereoselectivity for the trans-isomer can be achieved with the use of bulky diazoacetates such as BDA" 187 or DCM97 188. 

The rule can be used for the stereochemical differentiation of hydrogens (or methyl groups) os to the carbonyl group in cyclohexanones ASIS are + 0.2 to + 0.4 in the axial case, whereas they are much smaller, though still positive, in the equatorial case A5 +0.06 to + 0.1)235. Further examples have been collected232, and a method of estimating 13C ASIS has been described236. 

Diastereomeric 1,3-amino alcohols 1 have been obtained by reduction of 4,5-dihydroisoxa-zoles350-353. 3C chemical shifts allow a stereochemical differentiation due to the formation of energetically preferred chelated conformations. Similar to /3-hydroxy carbonyl compounds and 1,3-diol derivatives, the chemical shifts of the backbone carbons are larger in the syn 1,3-amino alcohols than in the awn -isomers353. 

The diastereomeric 2,4-dimethyloxetanes can be easily distinguished by their H-3 signals since they are equivalent in the rran.s-isomer (nte.w-form), but differ by nearly 1 ppm in chemical shift in the c -isomer (d,/-form)474. This chemical shift difference is large enough to justify the expectation that a stereochemical differentiation should also be possible if the substituents in the 2- and 4-positions are different and, therefore, the H-3 atoms no longer equivalent in the tran.s-diastereomer. 

S.P. Gaucher, J.A. Leary, Stereochemical differentiation of mannose, glucose, galactose, and talose using zincfll) diethylenetriamine and ESI ion trap MS, Anal. Chem., 70 (1998) 3009. 

On examination of these compounds, it was surprising to observe that the 3S,4S benzamide 38 was almost as potent as its 3i ,4S isomer 34 in increasing the threshold to shock in the mouse MEST model (see table 2) [36]. Interestingly, there is a similar stereochemical differentiation in the cis series to that seen in the trans series because the 3R,4R enantiomer 39, unlike compound 38, did not demonstrate any anticonvulsant activity at the dose of 10 mg/kg employed. Moreover, compound 38 had little effect on blood pressure (-5 + 3%) after an i.v. infusion of 10 mg/kg over 0.5 hr to anaesthetised Hooded Lister rats, whereas its enantiomer 39 caused a fall of 36 + 7% at the same dose. 

On first inspection, the enamine Michael addition appears to be a mechanistically simple reaction where neutral starting materials go to neutral products. Stereochemical studies have revealed, however, that the process is exceedingly complex. Initially, at least four different types of product (not counting stereoisomers ) can be obtained prior to hydrolysis (see Scheme 3). The point at which stereochemical differentiation occurs has yet to be convincingly... 

As in the uncatalyzed reactions with enamines (vide supra), there is potentially more than one point where stereochemical differentiation can occur (Scheme 59). Selectivity can occur if the initial addition of the enol ether to the Lewis acid complex of the a,/J-unsaturated acceptor (step A) is the product-determining step. Reversion of the initial adduct 59.1 to the neutral starting acceptor and the silyl enol ether is possible, at least in some cases. If the Michael-retro-Michael manifold is rapid, then selectivity in the product generation would be determined by the relative rates of the decomposition of the diastereomers of the dipolar intermediate (59.1). For example, preferential loss of the silyl cation (or rm-butyl cation for tert-butyl esters step B) from one of the isomers could lead to selectivity in product construction. Alternatively, intramolecular transfer of the silyl cation from the donor to the acceptor (step D) could be preferred for one of the diastereomeric intermediates. If the Michael-retro-Michael addition pathway is rapid and an alternative mechanism (silyl transfer) is product-determining, then the stereochemistry of the adducts formed should show little dependence on the configuration of the starting materials employed, as is observed. 

For practical reasons, the stereochemical results of acyclic and cyclic compounds are treated separately. In both cases, the reaction can be enantio- or diastereodifferentiating. In the first case, the stereochemical differentiation is controlled by the reagent and in the second case the stereochemical outcome is either determined by the chiral substrate or by both the chiral substrate and the chiral reagent (double stereodifferentiating reactions)81-83. 

From these results, it can be concluded that, as in the unsubstituted trimethylene, the reactive structure of optimal ISC is characterized by a face-to-face orientation of the radical centers and a CCC angle y slightly smaller than for the triplet minima. As the singlet PES drops steeply for small values of y, the triplet state yields preferably cyclic products. The conditions for optimal ISC are similar for both minima and therefore, the stereochemical differentiation... 

Young, D.A., H. Kolodziej, D. Ferreira, and D.G. Roux Synthesis of Condensed Tannins. Part 16. Stereochemical Differentiation of the First Angular 2S,3R) Profisetinidin Tetraflavanoids from Rhus lancea (Karee) and the Varying Dynamic Behaviour of Their Derivatives. J. Chem. Soc., Perkin Trans. 1, 2537 (1985). 

Chapman, O.L., J.A. Klun, K.C. Mattes, R.S. Sheridan, and S. Maini Chemore-ceptors in Lepidoptera Stereochemical Differentiation by Dual Receptors and Achiral Pheromone. Science 201, 926-928 (1978). 

Alkanes are compounds in which stereochemical differentiation results from their various possible conformations. A number of these compounds, especially with different substituents present in the chain, may exist as enantiomers or diastereoi-somers, that is, compounds that are optically active. Figure 2.10 shows Newman projections of six different conformations for a molecular fragment consisting of two adjacent carbon atoms with substituents. 

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