Bijvoet method

As usual in stereochemical research, four main approaches have been applied to the problem of assigning chiralities to optically active cyclophanes. They are listed in order of their reliabilities i) anomalous X-ray diffraction (Bijvoet method), ii) chemical correlations with compounds of known chiralities (preferably established by the Bijvoet method), iii) kinetic resolutions and/or asymmetric syntheses, iv) interpretation of chiroptical properties (mainly circular dichroism) on the basis of (sector) rules including theoretical methods. 

For [2.2]paracyclophane-4-carboxylic acid (25) as (—)(R) This result has been mentioned in a footnote in Ref. 1011 but seems never to have been published (see also Ref. 61). The chirality of this acid was correlated via its ( )-aldehyde with a levo-rotatory hexahelicene derivative which, according to the paracyclophane moiety at the terminal, had to adopt (A/)-helicity. Its chiroptical properties are comparable to those of hexahelicene itself101. For the (—)-bromoderivative of the latter the (A/)-helicity was established by the Bijvoet-method 102). In a later study, (—)para-cyclophane-hexahelicene prepared from (—)-l,4-dimethylhexahelicene with known chirality (which in turn was obtained with approximately 12% enantiomeric purity by asymmetric chromatography) confirmed these results. It should be mentioned that [2.2]paracyclophane-4-carboxylic acid (25) was the first planar chiral cyclophane whose chirality was determined 1041 (see also Ref.54 ). The results justmentioned confirmed the assignment (+)( ). 

Bromo[2.2]metacyclophane-4-carbonitril (60, which had previously been correlated with many optically active 4-monosubstituted, 4,14-homo-, 4,12- and 4,14-heterodisubstituted [2.2]metacyclophanes) 77,78) was chosen as a nicely crystalline reference substance lo6) its chirality (i ) as determined by the Bijvoet-method 106) contrasts with the previously assigned chirality based on results of a kinetic resolution 77) (vide infra), but agrees with the assignment by the coupled oscillator method (to the bisester 57) 1071 and by optical comparison and correlation 84... 

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 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. 

Among naturally occurring materials whose absolute configuration has been determined using the Bijvoet technique are Ferrichrome A (40), and vitamin B12 (41). The relevant properties of the molecules so far studied by the Bijvoet method are collected in Table 1. 

Because of the biological importance of many chelating organic molecules such as a-amino acids many of their absolute configurations (determined by the Bijvoet method (57)), are available. This means that the known absolute configuration of one centre in a molecule can be used to deduce that of other centres. This can be done in several ways, and has proved extremely useful in coordination chemistry. 

A number of cross-checks are available, for example, the Cotton effects of the complexes D(+)[Co(en)a]3+ (configuration established by Bijvoet method) and of D(+)[Co(+pn)3]3+ (configuration predicted by conformational theory) would be expected to be similar, and this was found to be the case (31). The configuration of L(—)[Co(—pn)s]3+ has also been established by a crystallographic study (30). 

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. 

The X-ray study was extended to a determination of absolute configuration. The problem of the phase angle was solved by the Bijvoet method taking advantage of the anomalous dispersion of copper radiation... 

In 1962, the AC of clerodin 7,32 a key compound of the clerodane diterpenes, was determined as shown in Figure 12 by the X-ray Bijvoet method.33 Since this AC was believed to be correct, clerodin 7 was then treated as a reference compound for newly isolated members of this diterpene family. For example, in 1974, the ACs of caryoptin 8 and 3-epicary op tin 9 were determined to be as shown by CD and/or chemical correlation with 7. 

In organosilicon chemistry the molecular structure and absolute configuration of only a few chiral silanes have been determined by the Bijvoet method. These... 

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