Thioethers enantiomerically pure

Oxidation of thioethers derived from the natural chirality pool , the readily available lactic acid and 3-hydroxybutyric acid, has been used in molar-scale preparation of enantiomerically pure sulfoxides methyl ( )-2-(phenylsulfinyl)acrylate and (K)-isopropenyl p-tolyl sulfoxide [107]. 

Nitrones were the first as well as the most widely used dipoles in asymmetric cycloadditions. The first report on the use of enantiomerically pure vinylsulf-oxides as dipolarophiles was due to Koizumi et al. [153], who described in 1982 the reaction of (-R)-vinyl p-tolyl sulfoxide 1 with acyclic nitrones 191. The reactions required 20 h in refluxing benzene to be completed, yielding a mixture of only two compounds, 192 and 193 (Scheme 91). They exhibited identical endo or exo stereochemistry (which was not unequivocally assigned), deduced from the fact that their reduction yielded enantiomeric thioethers. The major component, 192, exhibits (S) configuration at C-3, determined by chemical correlation. The authors claim this paper [153] to be the first example of 1,3-dipolar cycloaddition using chiral dipolarophiles. 

Enantiomerically pure sulfoxides are important intermediates in organic synthesis (21) and quite a number of pharmaceuticals and other biologically active compounds harbor a chiral sulfoxide unit (22). With respect to oxidation catalysis, enantiomerically enriched sulfoxides can either be accessed by asymmetric sulfoxidation of prochiral thioethers (Scheme 7, path a), or by kinetic resolution of racemic sulfoxides (Scheme 7, path b). For the latter purpose, enantio-specific oxidation of one sulfoxide enantiomer to the sul-fone, followed by separation, is the method of choice. 

Coordinated thioether S is often asymmetric. In (302) the asymmetry is frozen by the configuration of the attached chelate rings but in (301) it is not and inversion is fast. Conventional resolution via diastereoisomeric salts has never been substantiated for a purely enantiomeric Co—SR Ril+ system devoid of other chirality. I3C and H studies on diastereoisomeric systems1079 however show that inversion rates are normally of the order 0.1-10 s1, which makes coordinated thioethers decidedly more configurationally labile than organic sulfonium salts. The effects of asymmetry in (302) are readily seen in diastereoisomeric systems where the lone pair on S is often stereospecifically orientated. It usually directs stereochemical change and ligand replacement processes. 

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