Sulfides dioxirane oxidation

Chiral sulfides, dioxirane oxidation, 1156-7 Chlamydomonas reinhardtii, hydrogen peroxide determination, 646 y-Chlordene, isomers, 728 Chlorellajusca, hydrogen peroxide determination, 646... 

The by far more common and preparatively valuable dioxirane oxidation of divalent sulfur substrates is that of sulfides, to produce either sulfoxides or sulfones . Since sulfoxides are considerably less reactive than sulfides, the reaction outcome may be conveniently controlled by the stoichiometry of the oxidant For example, in the low-temperature oxidation of thiophene by an excess of DMD, the corresponding 1,1-dioxide (sulfone) has been obtained, albeit in low yield (equation 20). This is the first preparatively useful method for isolating this elusive sulfone, which also accentuates the importance of the neutral and anhydrous conditions under which the oxidations with the isolated DMD may be conducted. 

The enantioselective oxidation of prochiral sulfides with DMD has been achieved by using bovine serum albumin (BSA) as the chiral inductor Moderate to good enan-tioselectivities have been reported in the presence of this protein, for which a typical example is shown in equation 22 . As yet, however, no enantioselective oxidation of a prochiral sulfide has been documented by employing an optically active dioxirane. We have tried the enantioselective oxidation of methyl phenyl sulfide with the dioxirane generated from the ketone 7 (Shi s ketone), but an ee value of only ca 5% was obtained. One major hurdle that needs to be overcome with such enantioselective dioxirane oxidations is the suppression of the background oxidation of the sulfide substrate by Caroate, an unavoidable feature of the in-situ mode. 

In general, peroxomonosulfates have fewer uses in organic chemistry than peroxodisulfates. However, the triple salt is used for oxidizing ketones (qv) to dioxiranes (7) (71,72), which in turn are useful oxidants in organic chemistry. Acetone in water is oxidized by triple salt to dimethyldioxirane, which in turn oxidizes alkenes to epoxides, polycycHc aromatic hydrocarbons to oxides and diones, amines to nitro compounds, sulfides to sulfoxides, phosphines to phosphine oxides, and alkanes to alcohols or carbonyl compounds. 

TABLE 6C.10. Asymmetric Oxidation of Sulfides Ar-S-R by Dioxiranes Catalyzed by BSA at 4°C... 

Steric effects were responsible for the complete diastereocontrol observed in the oxidation of various 6-halopenicillins by dimethyl dioxirane (DMD). Only one of the two possible diastereomeric sulfoxides has been obtained in each case23 (Table 1). Scheme 3 shows that perborate oxidation of optically active sulfide 16 affords, with moderate diastereoselectivity (78% de), the (f )-sulfoxide 17,24 designed as chiral ligand for catalytic asymmetric synthesis. 

Dioxirane species have been found to be effective oxidants for sulfides to sulfoxides and sulfoxides to sulfones.411 The oxidations both appear to be electrophilic in nature. 

Determination of dimethyldioxirane concentration by the GLC method is as follows A standard solution of thioanisole (phenyl methyl sulfide) is prepared. The solution is usually 0.2 M in acetone, but other concentrations may be used. It is important to keep the sulfide in excess so that oxidation by the dioxirane will produce largely or exclusively the sulfoxide and not the sulfone. 

Dioxiranes, prepared from acetone and other aliphatic ketones by treatment with Oxone, can accomplish oxidations that are usually not achieved by Oxone itself [210, 211], Dioxiranes can be isolated by vacuum codistillation with the respective ketones [210], or else, they may be formed in situ and applied in the same reaction vessel [210, 211]. Examples of the applications of dioxiranes are epoxidations 210] and the oxidation of primary amines to nitro compounds [211], of tertiary amines to amine oxides [210], and of sulfides to sulfoxides [210] (equation 12). 

The formal addition of an oxygen atom across the carbonyl group gives rise to dioxiranes (equation 33). In practice, this reaction is effected with Oxone, and dimethyldioxirane (30) and other dioxiranes have been generated in solutions of their parent ketones.Dioxirane (30) has been implicated in oxidations of alkenes, sulfides and iinines. The formal addition of nitrogen across a carbon-oxygen double bond to afford oxaziridines has been reviewed (equation 34).There are also many methods available for the indirect conversion of carbonyl compounds to aziridines > and thiiranes using multi-step conversions. 

The oxidation of organic compounds with dioxirane reagents has emerged as an important synthetic method [93,94,95]. The effective use of dimethyldioxirane and methyl(trifluoromethyl)dioxirane for the mild and efficient oxidation of olefins, sulfides, amines, and saturated hydrocarbons naturally raised the question whether chiral versions of these reagents can be developed. 

Gonzalez-Nunez, M.E. Mello, R. Royo, J. Asensio, G. Monz6, I. Tomas, F. L6pez, J.G. Ortiz, F.L. Mechanism of the oxidation of sulfides by dioxiranes conformational mobility and transannular interaction in the oxidation of thianthrene 5-oxide. J. Org. Chem. 2004, 69, 9090. 

Oxidised sulfides, such as sulfones and sulfoxides, are important intermediates in chemical reactions for biological molecules and are used in metal separations. Syntheses of these compounds are typically achieved using stoichiometric oxidants, such as peracids and dioxiranes however, these chemicals are not atom efficient. Thus, the use of environmentally benign oxidants such as hydrogen peroxide is being explored for sulfide... 

Deubel feels that experiments coneeming fhianthrene 5-oxide (SSO) as a probe for the electronic character of oxygen-transfer reactions need to be reinterpreted. The SSO molecule has a sulfide group, which is attacked by electrophiUc oxidants, and a sulfoxide moiety, which is oxidized by nucleophilic oxidants. An AIM analysis of thianthrene 5-oxide reveals that there is an area of charge depletion at the sulfoxide group. The location of this area indicates that the attack of nucleophiUc oxidants on SSO is stericaUy hindered. Therefore, the SSO probe makes oxidants such as dioxiranes appear to be more electrophilic than they actually are. 

Oxone sulfoxidations can show appreciable diastereoselectiv-ity in appropriate cases, as demonstrated in eq 26. Enantio-selective oxidations of sulfides to sulfoxides have been achieved by buffered aqueous Oxone solutions containing bovine serum albumin (BSA) as a chiral mediator (eq 27). As little as 0.05 equiv of BSA is required and its presence discourages further oxidation of the sulfoxide to the sulfone. Oxone can be the active oxidant or reaction can be performed in the presence of acetone, trifluoroacetone, or other ketones, in which case an intermediate dioxirane is probably the actual oxidizing agent. The level of optical induction depends on structure of the sulfide and that of any added ketone. Sulfoxide products show ee values ranging from 1% to 89%, but in most examples the ee is greater than 50%. 

Dioxiranes have been successfully used for the selective oxidation of sulfides to sulfoxides (Eq. (8.1)) [11]. 

The oxirane oxidation of sulfides has found applications in organic synthesis [13, 14]. For example, sulfoxidation of disulfide 1 with dioxirane afforded disulfoxide 2 in 98% yield (Eq. (8.2)) [13]. 

These reactions are rapid and the sulfide is efficiently oxidized to sulfoxide as the only product with no over-oxidation to sulfone. The oxirane reaction [Eq. (1)] is thought to proceed via a direct oxygen transfer from the oxirane to the sulfide. In a recent mechanistic study [9] it was found that a hypervalent sulfurane is an intermediate in the oxidation of sulfides by dioxiranes. This intermediate is in equih-brium with the electrophilic zwitterionic intermediate formed as a result of electrophilic attack by the peroxide on the sulfide. 

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