Sulphides asymmetric oxidation

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... 

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. 

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%. 

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,... 

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]. 

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. 

Sulphides may be oxidized to sulphoxides by A -halogenocompounds such as Af-chlorosuccinimide. The modified polyamide iV-chloro-nylon-6,6 (NCN-6,6) functions similarly, and a recent paper describes the asymmetric oxidation of sulphides in the presence of optically active alcohols (Scheme 14), for example (—)-2-octyl alcohol. This oxidation reaction gave the corresponding optically active sulphoxides. Schrane 14 shows an example of a functional polymer applied as a reagent. Most functionalized polymers employed in such a numner are in the form of insoluble cross-linked resins - polymer supported reagents - and... 

The confined chiral Bronsted acid (152) has been shown to catalyse asymmetric oxidations of sulphides to sulphoxides with hydrogen peroxide (Scheme 54). The generality and high enantioselectivity of the described method could be compared even to the best metal-based systems and suggested utility in other asymmetric oxidations. ... 

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. 

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. 

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%. 

Both (R)-(-t-)- and (S)-(-)-tertiarybutylphenylphosphine sulphides (6) have been synthesised in high optical purity from (S)-(-)- and (R)-(+)-tertiarybutylphosphinothioic acids, respectively, by formation of the mixed anhydride (5) followed by borohydride reduction (Scheme 2). Reactions of the product (6) have been used to provide routes to optically active phosphinothioic iodides, phosphinodithioates and thioselenophosphinic acids of known configurations. A new method for the asymmetric synthesis of tertiary phosphine oxides has been reported.5 An Arbusov reaction of the optically active 1,3,2-... 

The chiral sulphamyloxaziridines are extremely useful in the asymmetric epoxidation of non-functionalized alkenes to 446406 (equation 147) and the oxidation of non-functional-ized sulphides to sulphoxides 447407 (equation 148). High enantioselectivity for both types of reactions was observed with asymmetric bias increasing as the temperature of the reaction is decreased. The fact that oxaziridine (4-) R,R) (444) gives products with the R, R,R) configuration while (—) (5,S) (445) gives products with the S, (S,S) configuration is... 

As non-toxic chiral Fe complexes have recently been used as catalysts [118-120], increased knowledge of their structure-reactivity relationships becomes pertinent. X-band CW-EPR spectra of [Fe °Cl(l)], reported by Bryliakov et al. [121], were found to be typical of high-spin S = 5/2 Fe complexes with EID K, 0.15. Using this complex, the conversion and selectivity of the asymmetric sulphide oxidation reaction was investigated in a variety of solvents. In previous studies [122], the active site was proposed to be the [Fe =0(l)] species. However an alternative active species was proposed [121]. Oxo-ferryl 7i-cation radicals are expected to have typical S = 3/2 spectra with resonances at geff 4... 

An asymmetric synthesis of 2-substituted norbornadienes relies on the diastereoselective cycloaddition of cyclopentadiene to the activated alkenyl sulphoxldes (220 X C02Me or S02Ph)These dienophiles were obtained by a self-induced chiral oxidation of the corresponding sulphide. 

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