Sulphides asymmetric

The use of optically active peracids for asymmetric oxidation of sulphides will be discussed in Section III dealing with the synthesis of optically active sulphoxides. 

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

TABLE 15. Asymmetric oxidation of sulphides, RXSR2, to optically active sulphoxides, R R2S—O... 

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. 

The modified Sharpless reagent was also successfully applied288 for the asymmetric oxidation of a series of 1,3-dithiolanes 248 to their S-monooxides 249 (equation 134). It was observed that the optical induction on sulphur (e.e. from 68 to 83%) is not significantly affected by the substituents R1 and R2. Asymmetric oxidation of a few aryl methyl sulphides by organic hydroperoxides in the presence of a catalytic amount of the optically active Schiff base-oxovanadium(IV) complexes gave the corresponding sulphoxides with e.e. lower than 40%289. 

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. 

Very low asymmetric induction (e.e. 0.3-2.5%) was noted when unsymmetrical sulphides were electrochemically oxidized on an anode modified by treatment with (— )camphoric anhydride or (S)-phenylalanine methyl ester299. Much better results were obtained with the poly(L-valine) coated platinum electrodes300. For example, t-butyl phenyl sulphide was converted to the corresponding sulphoxide with e.e. as high as 93%, when electrode coated with polypyrrole and poly(L-valine) was used. 

Asymmetric oxidation of this sulphide was also catalyzed by two isocytochromes P 450 purified from phenobarbital induced rat liver309. Both P 450 isocytochromes, termed PB-1 and PB-4, when reconstituted with purified rat liver NADPH-cytochrome P 450 reductase and cytochrome b5 afforded ethyl p-tolyl sulphoxide with S-configuration at the sulphur atom. In the case of PB-1 optical purity of this sulphoxide was 58% whereas with PB-4 it was 78%. 

Chiral alcohols have also been used in an asymmetric synthesis of sulphoxides based on halogenation of sulphides. Johnson and coworkers have found319 that the reaction of benzyl p-tolyl sulphide with JV-chlorobenzotriazole (NCBT) followed by addition of (—) menthol and silver tetrafluoroborate afforded diastereoisomeric menthoxysulphonium salts 267 which, upon recrystallization and hydrolysis, gave benzyl p-tolyl sulphoxide with 87% optical purity (equation 145). More recently, Oae and coworkers reported320 that optically active diaryl sulphoxides (e.e. up to 20%) were formed either by hydrolysis or thermolysis of the corresponding diaryl menthoxysulphonium salts prepared in situ from diaryl sulphides using ( —) menthol and t-butyl hypochlorite. 

In 1960, Montanari and Balenovic and their coworkers described independently the first asymmetric oxidation of sulfides with optically active peracids. However, the sulphoxides were formed in this asymmetric reaction (equation 130) with low optical purities, generally not higher than 10%. The extensive studies of Montanari and his group on peracid oxidation indicated that the chirality of the predominantly formed sulphoxide enantiomer depends on the absolute configuration of the peracid used. According to Montanari the stereoselectivity of the sulphide oxidation is determined by the balance between one transition state (a) and a more hindered transition state (b) in which the groups and at sulphur face the moderately and least hindered regions of the peracid,... 

Much higher asymmetric induction was observed in the two-phase oxidation of simple alkyl aryl and diaryl sulphides , substituted alkyl aryl sulphides and dithioacetals of formaldehyde by sodium metaperiodate in the presence of proteins such as bovine serum y-globulin and egg albumin. Optical purities of the sulphoxides so formed ranged between 20 and 85%. 

The first reductive kinetic resolution of racemic sulphoxides was reported by Balenovic and Bregant. They found that L-cysteine reacted with racemic sulphoxides to produce a mixture of L-cystine, sulphide and non-reduced optically active starting sulphoxide (equation 147). Mikojajczyk and Para reported that the reaction of optically active phosphonothioic acid 268 with racemic sulphoxides used in a 1 2 ratio gave the non-reduced optically active sulphoxides, however, with a low optical purity (equation 148). It is interesting to note that a clear relationship was found between the chirality of the reducing P-thioacid 268 and the recovered sulphoxide. Partial asymmetric reduction of racemic sulphoxides also occurs when a complex of LiAlH with chiral alcohols , as well as a mixture of formamidine sulphinic acid with chiral amines, are used as chiral reducing systems. ... 

In Figure 13.19 we have shown a route to L-699,392 published by Merck involving three steps based on homogeneous catalysts, viz. two Heck reactions and one asymmetric hydrogen transfer reaction, making first an alcohol and subsequently a sulphide [21], Stoichiometric reductions for the ketone function have been reported as well [22] and the Heck reaction on the left-hand side can be replaced by a classic condensation reaction. L-699,392 is used in the treatment of asthma and related diseases. 

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. 

Sulphides are oxidized readily by most hypervalent iodine reagents. IOB alone is not suitable, since mixtures of sulphoxides and sulphones are formed under drastic conditions. However, in the presence of catalytic amounts of p-toluenesulphonic acid [49] or benzeneseleninic acid [50] various sulphides were cleanly oxidized to sulphoxides in excellent yields. Using a chiral catalyst asymmetric oxidation was highly successful [51]. 

The analogues [menthyloxy(tosyloxy)iodo]benzenes, with both (+) and (-) forms of menthol, in their reactions with non-symmetric sulphides caused considerable asymmetric induction hydrolysis of their salts afforded sulphoxides of high optical purity [52]. By using A-phenyliodonio tosylates of benzamide (and some other similar derivatives from different amides, Section 7.4.1) dimethyl sulphide was converted into amidosulphonium tosylates which can serve as the precursors of sulphilimines [51] ... 

Similar to alkoxy radicals, few organic thiyl radicals have been observed in photochemical liquid systems. However, asymmetric spectra attributed to RS radicals with anisotropic g-tensors, have been observed in UV-irradiated thiols, sulphides, and disulphides in a solid matrix at 77°K (103,242-245). A typical "sulfur pattern" is shown in Figure 10, and the typical values... 

Dithiophosphate groups in PhAs[S2P(OPr )j]2 chelate in an asymmetric fashion with As—S distances of 2.310/2.317 and 3.135/3.187 A to give a square-pyramidal arrangement about arsenic , and when bis(dimethylarsino)sulphide, (Me2As)2S, coordinates to dimeric trimethylplatinum bromide it does so via the arsenic atoms and bridges between the two Pt atoms The arsenic-sulphur distances are normal with an As—S—As angle... 

Horseradish peroxidase (HPO) has been reported to be threefold more stable at 80°C in 5-10% [bmim+][BF ] as compared to phosphate buffer [28], Okrasa et al. [29] reported the asymmetric oxidation of phenyl methyl- and 2-naphthyl methyl sulphides to sulphoxides catalysed by peroxidase from Coprinus cinereus in [bmim ] [PP6-] with 10% water [29], Although the enantioselectivity (63-92% ee) and yields (<32%) were similar to those in water, the reaction workup was easier because ionic liquids and the extraction solvent did not form emulsions. 

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