Determination of absolute configuration

The determination of the absolute configuration of a compound is a decisive step in the characterization of an enantiomer. A range of physical and chemical methods is available for this, and often it is a combination of the two that leads to a solution. The problem of determining the absolute configuration can be posed as follows by using a descriptor (R), 

We have seen that the enantiomers of a molecule have the same properties (melting and boiling points, refractive index, etc.) and that spectroscopy that does not involve polarized light is incapable of distinguishing between them, so that their infrared, NMR, ultraviolet-visible and Raman spectra are identical. On the other hand, the optical rotation, optical dispersion and circular dichroism give results that are opposite in sign for the two enantiomers. We have also seen that in certain cases it is possible to determine the absolute configuration of a molecule in the crystal by X-ray diffraction. 

View of the Cinchonidinium cation (left) and of the Trisphat anion (right). 

In the absence of what may be termed a chiral probe to establish the absolute configuration, it is nevertheless possible in some cases to reach the absolute configuration by an X-ray diffraction study of a single crystal. This is how Bijvoet determined the absolute configuration of sodium rubidium bitartrate (+)-NaRb tartrate (2.5)-NaRb. 

structural calculation from the diffractogram allows the Flack s parameter to be determined automatically. This is equal, or very close, to zero if the absolute configuration attributed to the molecule is correct, and is equal to unity in the case of the opposite configuration. It is equal or close to 0.5 if the two configurations are present in equal amounts in the crystal. 

---

Almost all the entries in Chapters 4, 5 and 6 have CAS (Chemical Abstract Service) Registry Numbers to identify them, and these have been entered for each substance. Unlike chemical names which may have more than one synonymous name, there is only one CAS Registry Number for each substance (with only a few exceptions, e.g. where a substance may have another number before purification, or before determination of absolute configuration). To simplify the method for locating the purification of a substance, a CAS Registry Number Index with the respective page numbers has been included after the General Index at the end of the book. This will also provide the reader with a rapid way to see if the purification of a particular... 

Discovery of Optically Active Molecules and Determination of Absolute Configuration... 

The C-3,C-7 notation is also used where the choice between the C-3,C-6 and C-3,C-7 notation in the literature has been arbitrary. Only in cases like (—)-anisodamine 63 (vide infra), where the determination of absolute configuration is on a solid basis and where the structure is correctly presented by the C-3,C-6 notation also in the present numbering system, has the original... 

Scheme 24. Determination of absolute configuration using lead tetraacetate oxidation.

Krow, G., The Determination of Absolute Configuration of Planar and Axially Dissymmetric Molecules, 5, 31. 

Readers may refer to the latter part of this chapter for the determination of absolute configuration. 

This chapter has provided a general introduction to stereochemistry, the nomenclature for chiral systems, the determination of enantiomer composition and the determination of absolute configuration. As the focus of this volume is asymmetric synthesis, the coming chapters provide details of the asymmetric syntheses of different chiral molecules. 

VIII. Determination of Absolute Configuration by Electron Microscopy.74... 

III. DETERMINATION OF ABSOLUTE CONFIGURATION AND OPTICAL PURITY OF CHIRAL SULFUR COMPOUNDS... 

The most reliable method for the determination of absolute configurations is based on the X-ray diffraction technique, which recently has become more accessible and efficient because of the availability of electronic computers and of automatic and semiautomatic diffractometers. 

Organosulfur chemistry is presently a particularly dynamic subject area. The stereochemical aspects of this field are surveyed by M. Mikojajczyk and J. Drabowicz. in the fifth chapter, entitled Qural Organosulfur Compounds. The synthesis, resolution, and application of a wide range of chiral sulfur compounds are described as are the determination of absolute configuration and of enantiomeric purity of these substances. A discussion of the dynamic stereochemistry of chiral sulfur compounds including racemization processes follows. Finally, nucleophilic substitution on and reaction of such compounds with electrophiles, their use in asymmetric synthesis, and asymmetric induction in the transfer of chirality from sulfur to other centers is discussed in a chapter that should be of interest to chemists in several disciplines, in particular synthetic and natural product chemistry. 

Crist, B.V. Li, X. Bergquist, P.R. Djerassi, C. (1983) Isolation, partial synthesis, and determination of absolute configuration of pulchrasterol. The first example of double bioalkylation of the sterol side chain at position 26. J. Org. Chem., 48,4472-9. 

A concise synthesis and determination of absolute configuration of (—)-neuchromenin, a neurotrophic metabolite of E. javanicum var. meloforme, has been described (Scheme 72) <2001EJ01963>. 

Determination of Absolute Configuration 4.2.2.1. Based on Anomalous Dispersion of X-rays Introduction... 

The determination of absolute configuration (or, more generally, absolute structure see Section 4.2.2.1.1.) is usually based on the small intensity differences of Friedel pairs, e.g., Im vs. 

If, for a set of reflections hkl, the Friedel opposites, or any other reflections equivalent by point group symmetry, have not been measured, a determination of absolute configuration can be attempted using the following method. The structure refinement (including anomalous scattering) is carried out separately for the two enantiomorphic models (one obtained from the other... 

Table 4. Determination of Absolute Configuration using Flack s Test...

Determinations of absolute configuration by internal comparison are becoming rather frequent (see Table 5) but they may be unreliable since occasionally authors seem to only assume the absolute configuration of the chiral reference component in the structure. 

Rearrangement of an achiral epoxide to give an optically active allyl alcohol, e.g., 1, induced by enantioselective deprotonation with a homochiral base (see p 436 for the determination of absolute configuration)55. 

Related to this is the use of amino acid derived reagents for resolution of racemic carbonyl compounds and determination of absolute configurations by X-ray analysis at the imine stage. This is exemplified by the L-valinol derived imine of tricarboxyl (l-formyl-2-methoxyphenyl) chromium (see p 417)88. 

---