Bijvoet analysis

Less reliable than genetic change and far less reliable than a Bijvoet analysis is the attempt to establish the direction of molecular twist by optical rotatory dispersion, where the optical rotations of the compound are plotted against the various wavelengths of light at which they were determined (Djerassi, 1960). This method can be misleading except for quite simple molecules. 

Table 3. Determination of the Absolute Configuration by Analysis of Bijvoet Differences for Compounds Containing Only Oxygen Atoms as Anomalous Scatterers...

In a similar way the absolute configuration R at phosphorus was assigned to (-) O-ethyl O-isopropyl phosphorothioic acid (1A j. (-) 0-ji-butyl O-isopropyl phosphorothioic acid Q5) and (+) 0-me-thyl O-naphthyl phosphorothioic acid (1 6). The correctness of the configurational assignments was checked by X-ray analysis of (+)--S-methyl O-methyl O-naphthyl phosphorothioi ate (1 7) by means of the Bijvoet method. 

The degradation work had up to this point occupied itself mainly with the proof of the gross skeletal structure, and relatively little attention had been given to the stereochemistry of the molecule. It was at this point that this aspect of the problem was cleared by the determination of the structure of strychnine by X-ray crystallographic analysis independently by Robertson and Beevers (35) and Bijvoet et al. (36). 

A similar deduction furnishes a similar condition for the three-dimensional problem, in which i/X and mja are now vectors in a reciprocal space, well known in crystallography (Bijvoet et al., X-ray Analysis), quoted on p. 103). 

But how do we know in the first place that (—)-2-methyl-l-butanol has configuration III Its configuration was related in this same manner to that of another compound, and that one to the configuration of still another, and so on, going back ultimately to (4-)-tartaric acid and Bijvoet s x-ray analysis. 

Conformationally Controlled Gas-Solid Brominations in Racemic and Enantiomeric Crystals.—The above approach is elegant because any observed asymmetric induction is a direct consequence of the chirality of the crystal. However, the method does not permit a systematic analysis for the following reasons (/) only a small percentage of non-chiral molecules form chiral crystals, (//) it is not always feasible to prepare large homochiral crystals needed for the experiment, (m) the absolute configuration of both the starting crystal and the products formed requires application of the Bijvoet method of anomolous X-ray scattering, which is sometimes difficult to apply for molecules that do not contain heavy atoms. 

To determine the absolute configuration of optically active organic compounds, there are two nonempirical methods. One is the Bijvoet method in the X-ray crystallographic structure analysis, which is based on the anomalous dispersion effect of heavy atoms. - The X-ray Bijvoet method has been extensively applied to various chiral organic compounds since Bijvoet first succeeded in determination of the absolute stereochemistry of tartaric acid in 1951. The second method is a newer one based on the circular dichroism (CD) spectroscopy. Harada and Nakanishi have developed the CD dibenzoate chirality rule, a powerful method for determination of the absolute configuration of glycols, which was later generalized as the CD exciton chirality method. 8 The absolute stereochemistry of various natural products has been determined by application of this nonempirical method. 

Despite repeated recrystallizations, both diastereomers 43a and 43b were obtained only as amorphous solids. Therefore, the first-eluted fraction (-)-43a was reduced with LiAlH4 to yield enantiopure glycol (-)-42, which was further converted to 4-bromobenzoate (-)-44 (Fig. 9.7a). By recrystallization from EtOH, (-)-44 gave good single crystals suitable for X-ray analysis, and consequently its absolute configuration was explicitly determined as S by the Bijvoet pair measurement of the anomalous dispersion effect of the bromine atom contained (Fig. 9.7b) [40]. 

If the crystal-structiu-e analysis is made on a derivative containing a heavy atom, with x-rays of wavelength appropriate to the particular heavy atom (that is, Br or I with CuKa radiation), it is possible to determine the absolute configuration of an enantiomorphous molecule. This method was first demonstrated with the rubidium sodium salt of dexiro-tartaric (l-threaric) acid tetrahydrate by Bijvoet and coworkers in 1951. The results confirmed the configuration of dextro-i vi nc acid originally assigned by... 

When a very narrow X-ray beam (with a spread of wavelengths) is directed on the center of a genuine pearl, all the crystallites are irradiated parallel to a trigonal axis and the result is a Laue photograph with 6-fold symmetry. In a cultured pearl the narrow beam will have an arbitrary orientation with respect to the crystallite axes (of the central core) and an unsymmetrical Laue photograph will result. (See J. Bijvoet et al., X-ray Analysis of Crystals. Butterworth (1951).)... 

At present there is a large amount of experimental data available - mostly X-ray dif action studies, (Stem and Beevers, 1950 Van Bommel, Bijvoet,1958 Tapscott et al., 1969 Rychlewska, 1992 Szczepahska et al., 1994-1995) VCD, (Polvarapu et al, 1985 Su and Keiderling, 1980) ROA, (Barron, 1978 Barron et al., 1992) NMR (Ascenso and Gil, 1980 Hasa, 1980) measurements and dibenzoate exciton chirality analysis (Gawrohski et al., 1989) for both ionic and covalent derivatives of (R,R)-tartaric acid (Fig. la). 

But absolute configurations can be obtained from an analysis of small differences in diffraction intensities by a method developed by J.M. Bijvoet. The method makes use of extra phase shifts that occur when the frequency of the X-rays approaches an absorption frequency of atoms in the compound. The phase shifts are called anomalous scattering and result in different intensities in the diffraction patterns of different enantiomers. See Section 2.3.7(b) of the 7th edition of this text for an explanation of the origin of this anomalous phase shift. The incorporation of heavy atoms into the compound makes the observation of the extra phase shift easier to observe, but with very seasitive modern diffractometers this is no longer strictly neces.sary. 

Other representations of 48 and 49 are also shown, including the normal line notation used with other molecules in this book. Fischer assigned (d) to the (+) enantiomer (which happens to be dextrorotatory), but this was an arbitrary choice (a guess that is properly called an assiunption). Remember from Chapter 9 (Section 9.2) that (+) and (-) refer to specific rotation, which is a physical property, whereas d and 1 are names. In 1851, Johannes Martin Bijvoet (the Netherlands 1892-1980) showed by x-ray analysis that Fischer s assignments were correct. 

Because the crystalline material (called, at that time, vincaleucoblastine) had what were reported to be interesting properties, further examination was undertaken, physical data were collected, and suggestions for the structure based on spectroscopic analysis were set forth. Finally, the X-ray crystal structure, using the Bijvoet method of anomalous dispersion vide supra), succeeded in establishing the structure and stereochemistry beyond reasonable doubt. 

In 1951, the Dutch crystallographer Johannes Bijvoet established the absolute configurations of these compounds by the X-ray diffraction analysis of a salt of tartaric acid, which had been correlated by chemical means with Fischer s sugars and, in turn, glycCTaldehyde. As Bijvoet states in his papa- (abbreviated), The result is that Emil Fischo- s convention. . . appears to answer the reality. Lucky guess ... 

Careful analysis by other experts in the chiroptical techniques, however (S. F. Mason, Chem. Comm., 1973, 239 A. M. F. Hezemans and M. P. Groenewege, Tetrahedron, 1973, 29, 1223) and by X-ray crystallographers, now indicates that the error lay in the method used for the calculation of the absolute configurations from the spectroscopic data, and that the Bijvoet method is indeed correct. This interlude did show, however, how slender is the thread of argument, albeit correct, on which the Bijvoet assignments are made, and also how few chemists are truly competent to pass judgement on these matters. 

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