Sulfoxides, dioxirane oxidation

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. 

C-H bond unreactive to insertion, 1160 dioxirane oxidation, 1156 Sulfonic acids, C-H bond unreactive to insertion, 1160 Sulfonyl endoperoxides parasiticidal activity, 1309 synthesis, 1306-9, 1332 Sulfonyl peroxides, 1001-2, 1004-7 Sulfonylperoxy radical, superoxide reactions, 1035-9 Sulfoxidation... 

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. 

E)-3-Arylidenethiochroman-4-oncs possess thioether and oi,[)-unsaturatcd ketone functionalities both of which are susceptible to oxidation by DMD. In fact, chemoselective oxidation at sulfur is observed with a separable mixture of the sulfoxide and sulfone being produced in >5 1 ratio. A similar situation holds for the related thioflavanones. Epoxidation of the alkenic double bond in the thiochromanone 1,1-dioxides alone can be achieved using methyl(trifluoromethyl)-dioxirane (Scheme 65) <1994T13113>. However, reaction of NaOCl with 3-arylidenethioflavanones gives the epoxide and subsequent oxidation with DMD then gives a mixture of the sulfoxide and sulfone <2003MRC193>. 

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. 

Major interest has been expressed in the synthesis of chiral sulfoxides since the early 1980s, when it was discovered that chiral sulfoxides are efficient chiral auxiliaries that are able to bring about important asymmetric transformations [22]. Sulfoxides are also constituents of important drugs (e.g., omeprazole (Losec , Priso-lec )) [23]. There is a plethora of routes of access to enantioenriched sulfoxides, and many involve metal-catalyzed asymmetric oxidations [24]. Examples of ruthenium metal-based syntheses of sulfoxides are scarce, presumably due to the tendency of sulfur atoms to bind irreversibly to a ruthenium center. Schenk et al. reported a dia-stereoselective oxidation of Lewis acidic Ru-coordinated thioethers with dimethyl-dioxirane (DMD) (Scheme 10.16) [25[. Coordination of the prochiral thioether to the metal is followed by diastereoselective oxygen transfer from DMD in high yield. The... 

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). 

Oxygen transfer to sulfur, which leads to sulfoxides and/or sulfones are displayed in Scheme 6. Excess dioxirane converts bis-thiophenylmethane into its bis-sulfone [23] 29 quantitatively. When using stoichiometric amounts of dioxirane, thioenol ethers are transformed into their sulfoxides [23] 30, but excess dioxirane leads to the sulfone [23] 31. As expected, the thioisoflavone [24] 32, the allene sulfoxide [25] 33, and the bis-methylthiobutadiene [26] 34 gave the corresponding sulfones even when excess dioxirane was employed. Of potential synthetic value is the direct oxidation of thioesters to oxo sulfones [27] 35. Finally, diphenyl disulfide afforded the S-thiosulfinate [23] 36 as major product when dioxirane was used in stoichiometric quantity. 

Examples of sulfur oxidation constitute the sulfone of the ruthenium complex and the sulfoxide of the tungsten derivative [37]. In the latter, an excess of dioxirane effected the oxidation to the corresponding sulfone. Oxyfunctionalizations of this type are unprecedented. 

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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