Chiral absolute configurations

The first assignment of the chirality (absolute configuration) to a planar chiral phane ([2.2]paracyclophanecarboxylic acid 23, in 1968),04) was deduced from the results of a kinetic resolution of its (racemic) anhydride with (—)-l-phenylethyl-amine and is based on the related topology of 23 and 2-methyl-metallocene-l-carb-oxylic acids 19). For these chiral compounds, this method had given (correct) results, as confirmed afterwards by the Bijvoet method 109). Since this method has been reviewed in some detail19,100) it will not be discussed in this survey. 

In 1951, Johannes Martin Bijvoet used such differences in intensity, resulting from anomalous scattering by an atom in a noncentrosymmetric crystal, to determine the chirality (absolute configuration) of the tartrate ion. Details of this method, which has been used extensively for finding the absolute configurations of natural products and for determining macromolecular structures, are given in Chapter 14. 

The R, S convention is a scheme which has largely superseded the D, i. system to denote configuration about a chiral centre in a molecule. The convention allows unequivocal designation of the absolute configuration in a description of the positions in space of ligands attached to a chiral centre, in relation to an agreed standard of chirality like a right-hand helix. 

All the double bonds are cis and the absolute configuration of the chirality center is S Wnte a stereochemically accurate representation of ectocarpene... 

The same cannot be said about reactions with alkyl halides as substrates The conver Sion of optically active 2 octanol to the corresponding halide does involve a bond to the chirality center and so the optical purity and absolute configuration of the alkyl halide need to be independently established... 

Techniques for determining the absolute configuration of chiral molecules were not developed until the 1950s and so it was not possible for Eischer and his contemporaries to relate the sign of rotation of any substance to its absolute configuration A system evolved based on the arbitrary assumption later shown to be correct that the enantiomers... 

Absolute configuration (Section 7 5) The three dimensional arrangement of atoms or groups at a chirality center Acetal (Section 17 8) Product of the reaction of an aldehyde or a ketone with two moles of an alcohol according to the equation... 

FIGURE 1.19 Viewing angle as a means of designating the absolute configuration of compounds with a chiral axis, (a) (R )-2-Butanol (sequence clockwise) (b) (fi)-2-butanol (sequence counterclockwise). 

The chiralities at C-6 of natural 5,6,7,8-tetrahydrofolic acid and related folates, e.g. 5,10-methylene-, 5-methyl- and 5-formyl-5,6,7,8-tetrahydrofolic acid, from various biological systems are the same and possess the absolute configuration (S) at C-6 as deduced from an X-ray study of the ion (51) (79JA6114). 

Nitrogen chirality may also be produced by the action of an achiral peroxyacid on a Schiff base containing a chiral amine (75JOC3878). In this case the oxaziridine contains a configurationally known centre of chirality relative to this, absolute configurations of the centres of chirality at nitrogen and carbon, and thus the complete absolute configuration of the molecule, can be determined (see Section 5.08.2.2). 

The presence of asymmetric C atoms in a molecule may, of course, be indicated by diastereotopic shifts and absolute configurations may, as already shown, be determined empirically by comparison of diastereotopic shifts However, enantiomers are not differentiated in the NMR spectrum. The spectrum gives no indication as to whether a chiral compound exists in a racemic form or as a pure enantiomer. 

If the amount of the sample is sufficient, then the carbon skeleton is best traced out from the two-dimensional INADEQUATE experiment. If the absolute configuration of particular C atoms is needed, the empirical applications of diastereotopism and chiral shift reagents are useful (Section 2.4). Anisotropic and ring current effects supply information about conformation and aromaticity (Section 2.5), and pH effects can indicate the site of protonation (problem 24). Temperature-dependent NMR spectra and C spin-lattice relaxation times (Section 2.6) provide insight into molecular dynamics (problems 13 and 14). 

The spatial aiiangement of substituents at a chirality center is its absolute configuration. Neither the sign nor the magnitude of rotation by itself can tell us the absolute configuration of a substance. Thus, one of the following structures is (-l-)-2-butanol and the other is (—)-2-butanol, but without additional infonnation we can t tell which is which. 

We can use straightforward reasoning to come up with the answer. The absolute configuration at C-2 may be R or S. Likewise, C-3 may have either the R or the S configuration. The four possible combinations of these two chirality centers are... 

Absolute configuration (Section 7.5) The three-dimensional arrangement of atoms or groups at a chirality center. 

Cahn-Ingold-Prelog notation (Section 7.6) System for specifying absolute configuration as / or S on the basis of the order in which atoms or groups are attached to a chirality center. Groups are ranked in order of precedence according to rules based on atomic number. 

Optical resolution of the dithiirane 1-oxides 2 and 3 was accomplished by HPLC equipped with a chiral column (97T12203). Absolute configurations of 2a and 2b were determined by X-ray crystallography. Tire stereospecific isomerization (epimerrzation) of 2a to 3b and 2b to 3a was observed during the resolution study. 

The absolute configuration of products obtained in the highly stereoselective cycloaddition reactions with inverse electron-demand catalyzed by the t-Bu-BOX-Cu(II) complex can also be accounted for by a square-planar geometry at the cop-per(II) center. A square-planar intermediate is supported by the X-ray structure of the hydrolyzed enone bound to the chiral BOX-copper(II) catalyst, shown as 29b in Scheme 4.24. 

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