Chirality sulfur atom

Sulfoximines bearing a chiral sulfur atom have recently emerged as valuable ligands for metal-catalysed asymmetric synthesis.In particular, C2-symmetric bis(sulfoximines), such as those depicted in Scheme 1.51, were applied to the test reaction, achieving enantioselectivities of up to 93% ee. The most selective ligand (R = c-Pent, R = Ph) of the series was also applied to the nucleophilic substitution reaction of l,3-diphenyl-2-propenyl acetate with substituted malonates, such as acetamido-derived diethylmalonate, which provided the corresponding product in 89% yield and 98% ee. 

The most active chiral catalysts used to date employing a chiral sulfur atom as a unique source of chirality were reported very recently by Ellman s group. Hence, a novel bis(suffinyl)imidoamidine (siam) ligand, readily available, was proved to catalyse, in the presence of Cu(SbFe)2, the Diels-Alder reaction of a... 

The first example of asymmetric induction in transfer of chirality from the chiral sulfur atom to the prochiral carbon atom was described by Goldberg and Sahli in 1965 (197). It concerns the pyrolysis of the optically active p-tolyl tra s-4-methylcyclohexyl sulfoxides 258. It was found that on pyrolysis at 200 to 250°C, optically active sulfoxides (R)-258 and (5)-258 yield optically active 4-methylcyclohexenes-l 259, with the absolute R and S configurations, respectively, at the newly formed chiral carbon atoms (Scheme 25). The optical purities of the 4-methylcyclohexenes-l that were formed depended largely on the temperature of pyrolysis. Thus, the values of 42 and 70% optical purity were noted for 259 at 250° and 200°C, respectively. The formation of the cycloolefins 259, whose absolute configurations are the same as those of the starting optically active sulfoxides 258, indicates that the pyrolysis reaction proceeds... 

Pradilla et al. [140] have recently produced a nice paper showing that enan-tiopure hydroxy 2-p-tolylsulfinyl butadienes 158 (Scheme 78) undergo a highly face-selective Diels-Alder cycloaddition with AT-phenyl maleimide and phenyl-triazolidine dione, presumably controlled by the chiral sulfur atom (dienophile approach from the upper face of diene). Complementary 7r-facial selectivity (dienophile approach from the bottom face of diene) is displayed by related enantiopure sulfonyldienes 158 (Scheme 78). The authors suggest that the behavior of 158 is a consequence of the predominant influence of the chiral sulfur with respect to the hydroxylic carbon (the only chiral center in 158 ) on the stereochemical course of the cycloadditions. According to their explanation, dienes will adopt conformations similar to those depicted in Scheme 78, with the chiral centers employing their stereochemistry to maximum effect due to 1,3-allylic strain (which is considered as the main directing effect of these cycload-... 

With regard to isomerizations of double bonds, sulfinyl enynes gave unexpected results when submitted to PKR. These chiral substrates were thought to give high asymmetric inductions due to the proximity of the chiral sulfur atoms to the reaction centers. Surprisingly, both cis and trans ferf-butyl vinyl sulfoxides (237-238) were transformed into the same PK diastereoisomer 239 with high ee and moderate yields (Scheme 67) [103,104]. 

A recent report details absolute stereochemical control at levels of up to 75 25 in ene reactions, although typical levels are lower35. This selenium reagent has two identical, chiral sulfur atoms and it is these stereogenic centers that provide for reagent-based control of absolute stereochemistry. 

The type 11 CSPs have been used to resolve a wide variety of pharmacologically active compounds, both with and without derivatization (9-11). Some of the compounds that have been resolved without derivatization are hexobarbital (OA-CSP) (51), glutethimide (OB, OC, OK) (51), warfarin (OB, OC) (51), compounds containing a chiral sulfur atom (OB, OC) (52), verapamil (AD) (53), propranolol (OD) (54), and flurbiprofen (AD) (55), The resolution of the latter two compounds, propranolol, an ot, p-amino-alcohd, and flurbiprofen, a carboxylic acid, is representative of new applications for the cellulosic CSPs that are primarily used with hexane alcohol mobile phases. In the case of propranolol, the mobile phase was modified with N,N-dimethyIoctyl amine, and when flurbiprofen was chromatographed, trifluoroacetic acid was used as the modifier. 

The sulfonium ion (2), like a saturated carbon atom, possesses a tetrahedral configuration. The unshared electrons on the sulfur atom, however, unlike those of nitrogen in quaternary ammonium salts, can hold their configuration at ordinary temperatures. 1,2 Sulfonium salts containing three different groups (R, R and R" all different) consequently can exist as optical isomers, e.g. (2) and (3), owing to the presence of the chiral sulfur atom (Figure l).2... 

Williams and Cram47 prepared the cyclic sulfoximide 62, with a chiral sulfur atom, in three steps from 2-methylthio-5-methylacetophenone (59). The latter compound was converted into a 2-methylthiophenylacetic acid derivative (60), which was then oxidized to the 2-methylsulfinyl compound 61. Compound 61 was cyclized to 62 in 60% yield using sodium azide in sulfuric acid (Eq. 14).48... 

The HDA reaction of activated ketones is also possible using copper bis-oxazoline complexes. The highest ees in this procedure have been obtained using the copper complex prepared from the bis(sulfoximine) (8.141), which possesses chiral sulfur atoms and provides up to 98% ee in the HDA reaction of 1,3-cyclohexadiene (8.138) with substrate (8.142). 

Other elements can produce chiral centers besides carbon, although their importance in industry and in health studies is not as great. The sulfur atom can produce chiral centers for example the sulfoxides, sulfoximides, sulphonates and the sulfonium ion. An example of a chiral sulfur atom is given by the following sulfoxide structure. 

Ferrocenylmethylamine also functions as a chelating bidentate ligand, and the cyclometallated platinum complex contains a planar chirality. The complex with the cyclometallated (7V,A-dimethylamino)methylferrocene and methyl phenyl sulfoxide ligands 469 is obtained as a mixture of the two diastereomers having the planar chirality and chiral sulfur atom. ... 

Organic sulfonate esters, like sulfonyl halides, also readily undergo nucleophilic substitution reactions as previously mentioned (p 23). For example, oxygen-labelled (-)menthyl phenylmethanesulfonate 18 reacted with / -tolylmagnesium bromide to give labelled benzyl p-tolyl sulfone 19 with inversion of stereochemical configuration at the chiral sulfur atom (Equation 16). 

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