Enantiomeric sulfoxide

Owing to its conceptual simplicity and manifest utility, the direct liquid chromatographic separation of enantiomeric sulfoxides on chiral columns has also been attempted. Thus, Montanari et al. (32) found that racemic unsaturated vinyl disulfoxides 23 may be par-... 

Since in principle the reactions of enantiomeric sulfoxides with a chiral reagent are expected to proceed at unequal rates, a possibility exists for obtaining chiral sulfoxides, especially when the reacting racemic sulfoxide is used in excess in relation to the chiral reagent. A typical example of such a kinetic resolution of a racemic sulfoxide is its reaction with a deficiency of chiral peracid, affording a mixture of optically active sulfoxide and achiral sulfone (62,63). However,... 

NMR spectroscopy was found to be a valuable technique for differentiation between the enantiomers of optically active compounds. The principles of the methods used to distinguish between enantiomers by means of NMR have been developed and reviewed by Mis-low and Raban (217). The best results from the point of view of the determination of optical purity and absolute configuration of chiral sulfur compounds, especially of sulfinyl compounds, have been obtained with the help of chiral solvents (218). Pirkle (86) was the first to demonstrate that enantiomeric sulfoxides have nonidentical NMR spectra when dissolved in chiral alcohols having the following general formula ... 

An interesting method for the estimation of optical purity of sulfoxides, which consists of the combination of chemical methods with NMR spectroscopy, was elaborated by Mislow and Raban (241). The optical purity is usually determined by the conversion of a mixture of enantiomers into a mixture of diastereomers, the ratio of which may be easily determined by NMR spectroscopy. In contrast to this, Mislow and Raban used as starting material for the synthesis of enantiomeric sulfoxides a diastereomeric mixture of pinacolyl p-toluenesulfinates 210. The ratio of the starting sulfinates 210 was 60.5 39.5, as evidenced by the H NMR spectrum. Since the Grignard reaction occurs with full stereospecificity, the ratio of enantiomers of the sulfoxide formed is expected to be almost identical to that of 210. This corresponds to a calculated optical purity of the sulfoxide of 20%. In this way the specific rotations of other alkyl or aryl p-tolyl sulfoxides can conveniently be determined. 

It is of interest to note that the magnetic nonequivalence of the enantiomers of the a-phosphoryl sulfoxide 49 in the presence of TFMC was observed (88) not only in Hbut also in and NMR spectra. With regard to the accuracy of the NMR method, the P H NMR spectra proved very useful in this case, since only two well-separated singlets that were due to enantiomeric sulfoxides 49 were observed. 

Sulfides are generally oxidized much faster than alkenes, and in the presence of excess oxidant further oxidation to the sulfone occurs. In the cases where the reaction is conducted in an asymmetric way, the chiral catalytic system may react faster with one enantiomeric sulfoxide to form the sulfone than with the other, so that kinetic resolution of the primarily formed sulfoxide may occur. In general, the reaction is carried out with alkyl hydroperoxides like TBHP in the presence of a metal catalyst like Mo, W, Ti or V complexes. In some cases the sulfoxidation with hydroperoxides can take place without the need of a metal catalyst. Both examples will be discussed in the following. 

After the first discovery of the asymmetric sulfoxidation by Kobayashi et al. [226], it could be shown that a large number of aryl alkyl sulfides are oxygenated with enantiomeric excesses higher than 98% [227-229]. Other peroxidases also catalyze this reaction. Interestingly, the plant peroxidase HRP [230] yields the (S)-sulfoxide, whereas mammalian myeloperoxidase [223] and lactoperoxidase [231] catalyze the formation of the R-enantiomers. The stereospecific sulfoxidation of aryl alkyl sulfides by purified toluene dioxygenase (TDO) from P. putida was also studied in this context [232] and showed that sulfoxidation yielded the (S)-sulfoxides in 60-70% yield, whereas CPO under the same conditions yielded 98% (R)-sulfoxides (Scheme 2.15). CPO is thus again an exception from the rule in that it produces R-enantiomeric sulfoxides, besides its bacterial origin [227]. The reason for this behavior lies in the... 

Snyder s modification of the Wudl method is suitable for the synthesis of dialkyl and alkyl aryl sulfoxides in high ee. Both enantiomeric sulfoxides may be produced, either by reversing the order of organometallic displacement or by using the (IS, 2/ )-(+)-enantiomer of ephedrine, which is commercially available. Compared with... 

Using the DAG methodology, Noiret et al.142 synthesized the two enantiomeric sulfoxides 99(R) and 99(5) (Scheme 33) in high yield and selectivity, in order to study the mechanism of the in vivo desaturation of oleic acid.143... 

Addition of Eu(fod)3 or Pr(fod)3 to mixtures of enantiomeric sulfoxides and ben-zodiazepinones with 25 and 26 enhanced enantiomeric discrimination by an identical mechanism . The method was further extended to mixtures of chiral sulfoxides, amines and alcohols with 27. Warming the samples with lanthanide chelates to 50 °C reduced the exchange broadening to acceptable levels while retaining enantiomeric discrimination that was larger than observed with only the CSA . 

A.ii. Preparation of Chiral Sulfoxides. The sulfur atom in a sulfoxide has four different groups (R, R1, O, and the lone pair electrons). There is virtually no inversion at sulfur (in contrast to nitrogen) so the sulfur can be a stereogenic center under these circumstances, which raises two points when using unsymmetrical sulfoxides. The first is the presence of diastereomers that can complicate separation and identification. The second is the ability to resolve the enantiomeric sulfoxides or produce one enantio-selectively, and use this material as a chiral auxiliary or as a chiral template (sec. 10.9). 

The cyclic sulfite 1 was synthesized in good yield in two steps from (S)-ethyl lactate. Spedd conditions (slow addition of triethylamine to a mixture of diol and SOCI2) were needed to produce the trans-sulfite 1 (bans / cis = 90 10) which could be isolated in 70% yield after one crystallization. At this stage one may consider that the chiral diol has acted as a chiral conboller for the formation of an asymmetric sulfur atom. The conversion of 1 into enantiomeric sulfoxides 4 or 5 should be straightforward if the addition of the first organometallic R -M is chemoselective (no further attack of 2 or 3... 

The sulfinates (56) and (57) have been prepared in high yields by reaction of diacetoneglucose with tosyl- or mesyl-cyanide in the presence of DBU or DABCO, and the diasteres (+)(57) and (-)(57) were obtained in ca. 90% d.e. by use of methanesulfmyl chloride in pyridine or ethyldiisopropylamine, respectively. Their application to the synthesis of enantiomeric sulfoxides is referred to in Chapter 24. Carbohydrate sulfenates such as the glucofuranose derivative (58) and the glucopyranosyl derivative (59) were formed on treatment... 

Diacetone glucose has been used as a chiral auxiliary in the synthesis of enantiomeric sulfoxides. Treatment of the sugar derivative with methane-... 

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