Sulphoxides chiral

The sulphoxide moiety is pyramidal and therefore a potential stereogenic centre capable of inducing asymmetry at adjacent centres. Furthermore, it is chemically versatile and can be removed under mild conditions. These features render the sulphoxide group attractive as a chiral auxiliary. Solladie has employed sulphoxide-stabilised anions in an asymmetric synthesis of 3-hydroxyesters (76).P 1 

Two stereogenic centres are formed in the reaction between the anion (presumably a cyclic chelate) and the aldehyde but one is destroyed with the removal of the auxiliary, so its configuration is of no consequence. The nature of the aldehyde is important— acetylenic aldehydes give the opposite diastereomer (77).P9] 

So far all the chiral compounds have been of the conventional type, i.e. their stereogenic units have been tetrahedral carbon centres to which are attached four different substituents. The compounds (78) whose asymmetric synthesis is discussed below do not have a stereogenic centre they possess axial chirality. 

The resulting (/ )-sulphoxide (80) is then deprotonated by strong base at the methylene adjacent to the sulphur, and the resulting anion is 

The sulphoxide group undergoes clean 5y -elimination with the result that the (S, R) diastereomer is converted exclusively to the (/ )-enantiomer (81), while the (R,R) diastereomer gives its antipode (82). An alternative, third-generation approach to this type of compound is described in section 6.1.7. 

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Chiral sulphoxides are the most important group of compounds among a vast number of various types of chiral organosulphur compounds. In the first period of the development of sulphur stereochemistry, optically active sulphoxides were mainly used as model compounds in stereochemical studies2 5 6. At present, chiral sulphoxides play an important role in asymmetric synthesis, especially in an asymmetric C—C bond formation257. Therefore, much effort has been devoted to elaboration of convenient methods for their synthesis. Until now, optically active sulphoxides have been obtained in the following ways optical resolution, asymmetric synthesis, kinetic resolution and stereospecific synthesis. These methods are briefly discussed below. 

A convenient and simple route to chiral sulphoxides is an asymmetric oxidation of prochiral sulphides by optically active oxidizing reagents. 

A closely related asymmetric synthesis of chiral sulphoxides, which involves a direct oxidation of the parent sulphides by t-butylhydroperoxide in the presence of metal catalyst and diethyl tartrate, was also reported by Modena and Di Furia and their coworkers-28-7,288 jjje effect 0f the reaction parameters such as metal catalyst, chiral tartrate and solvent on the optical yield does not follow a simple pattern. Generally, the highest optical purities (up to 88%) were observed when reactions were carried out using Ti(OPr-i)4 as a metal catalyst in 1,2-dichloroethane. 

In contrast to the asymmetric procedures discussed above, the metal-catalyzed oxidation of alkyl aryl sulphides by t-butylhydroperoxide carried out in a chiral alcohol gives rise to chiral sulphoxides of low optical purity290 (e.e. 0.6 9.8%). Similarly, a very low asymmetric induction was noted when prochiral sulphides were oxidized by sodium metaperiodate in chiral alcohols as solvents291. 

Bis(4-hydroxyphenyl) sulphoxides butadienyl - see Butadienyl sulphoxides carbamoyl - see Carbamoyl sulphoxides chiral - see Chiral sulphoxides complexes of 567-573 conformational analysis of 84-89 cyclic - see Cyclic sulphoxides cyclopentanone - see Cyclopentanone sulphoxides... 

Aryl t-butylsulphoxides are sufficiently hindered for attack at sulphur to be less of a problem. The chiral sulphoxide offers no control over the new stereogenic centre in the reaction of 107 to give 108 (Scheme 46). 

The phase transitions of cholesteryl nonanoate have been studied with a new apparatus for thermal analytical microscopy. The enantiomer ratio of some chiral sulphoxides can be changed from racemic to a modest preference for one enantiomeric form by dissolution in a cholesteryl ester in its liquid-crystalline ( cholesteric ) state. 5,6-Epoxycholestan-3-yl p-nitrobenzoates exhibit liquid-crystal properties, but 5,6-diols and dibromides are inactive. ... 

Silicon (Si) and germanium (Ge) are in the same group of the periodic table as carbon, and they form tetrahedral compounds as carbon does. When four different groups are situated around the central atom in silicon, germanium and nitrogen compounds, the molecules are chiral. Sulphoxides, where one of the four groups is a nonbonding electron pair, are also chiral. 

Chiral compounds with silicon, germanium, and nitrogen stereooentres Chiral sulphoxide... 

The asymmetric oxidation of sulphides to chiral sulphoxides with t-butyl hydroperoxide is catalysed very effectively by a titanium complex, produced in situ from a titanium alkoxide and a chiral binaphthol, with enantioselectivities up to 96%342. The Sharpless oxidation of aryl cinnamyl selenides 217 gave a chiral 1-phenyl-2-propen-l-ol (218) via an asymmetric [2,3] sigmatropic shift (Scheme 4)343. For other titanium-catalysed epoxidations, see Section V.D.l on vanadium catalysis. 

Chiral sulphoxides, chiral phosphine, oxazolidinones, rerr.-butyl 2-methyl-.l-hydroxy-3-phenylpropionic acid thiocster... 

Delatour, P., Benoit, E., Caude, M. Tambute, A. (1990a) Species differences in the generation of the chiral sulphoxide metabolite of albendazole in sheep and rats. Chirality, 2, 156-160. 

A series of chiral sulphoxides, namely the p-tolylethyl, p-tolylmethyl, p-tolyl-isopropyl, p-tolyl-ten-butyl and p-tolyl-o-tolyl, has been, studied23). All showed large ROA below about 500 cm-1, especially in bands assigned to C—S—O deformations. It appears to be a general feature of both infrared CD and ROA that the presence of sulphur atoms greatly enhances the vibrational optical activity. 

E Kashiyama, T Todaka, M Odomi, Y Tanokura, DBJohnson, T Yokoi, T Kamataki, T Shimizu. Stereoselective pharmacokinetics and interconversions of flosequinan enantiomers containing chiral sulphoxide in rat. Xenobiotica 24(4) 369—377,1994. 

Stirling and coworkers incorporated a chiral sulphoxide group in a gold-thiol mono-layer (23). Quick exposure of this chiral monolayer to the vapours of ( )-ethyl lactate shows non-selective adsorption of both enantiomers. However, prolonged exposure at 40 °C results in adsorption of exclusively one enantiomer468. The interactions can be followed by SPR469. 

Chromans. - 2,4-Diethoxychromans (78) (mainly cis) represent a new type of chroman and have been prepared in high yield from a phenol (but not a deactivated phenol) and malonaldehyde bis(diethyl acetal) in the presence of SnCU they are converted into the benzopyrylium salts (79), in excellent yield, by treatment with perchloric acid. A Wittig-Horner reaction of the chiral phosphoryl ( S)-sulphoxide (81) and the ketone (80) gave the chiral sulphoxide (82), which was cyclized by aqueous alkali to a mixture which contained 22% diastereoisomeric excess of (25 )-chroman (i )-sulphoxide. This was converted, in three steps, into the aldehyde (83), which is a useful synthon for a-tocopherol. ... 

The chiral sulphoxide, (S)-(+)-2-(4-tolylsulphinyl)-2-cyclopentenone, has been used as a ring D component to effect an asymmetric Michael addition with 91-94% diastereoselectivity by reaction in the chelated form with the a,a-disubstituted lithium enolate from 2-bromo-6-methoxytetral-1-one while the (R)-(-) antipode reacts in a non-chelated form with the a-monosubstituted lithium enolate of 6-methoxytetralone (ref. 147). This synthesis makes use of earlier experience in the use of a-mono and a,a-disubstituted lithium enolates in the ethyl acetoacetate series with the non-chelated and chelated forms respectively of a p-ketosulphoxide (ref. 148). Eight futher steps were involved to produce (+)-estrone methyl ether in an overall yield of 6.3%. 

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