Sulfones dioxirane oxidation

Sulfur compounds with divalent sulfur functionalities are much more prone to dioxirane oxidation on account of their higher nucleophilicity compared to the above-presented oxygen-type nucleophiles. Examples of this type of dioxirane oxidation abound in the literature. Such a case is the oxidation of thiols, which may be quite complex and afford a complex mixture of oxidation products, e.g. sulfinic acids, sulfonic acids, disulfides, thiosulfonates and aldehydes , and is, therefore, hardly useful in synthesis. Nevertheless, the oxidation of some 9i/-purine-6-thiols in the presence of an amine nucleophile produces n >( -nucleoside analogs in useful yields (equation 19). This reaction also displays the general chemoselectivity trend that divalent sulfur functionalities are more reactive than trivalent sp -hybridized nitrogen compounds P. 

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. 

Alkyl hydroperoxysilanes, preparation, 783 Alkyl hydrotrioxides, structural chemistry, 132 Alkyl iodides, dioxirane oxidation, 1158 Alkyl methyl sulfonates, alkyl hydroperoxide synthesis, 673... 

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... 

Because C-H bonds are usually less reactive towards dioxirane oxidation than heteroatoms and C-C multiple bonds, it is instructive to give a few general guidelines on the compatibility of functional groups within the substrate to be submitted to oxidative C-H insertion Substances with low-valent heteroatoms (N, P, S, Se, I, etc.), C-C multiple bonds, and C=X groups (where X is a N or S heteroatom) are normally not suitable for C-H insertions, because these functionalities react preferably. Even heteroarenes are more susceptible to dioxirane oxidation than C-H bonds, whereas electron-rich and polycyclic arenes are only moderately tolerant, but electron-poor arenes usually resist oxidation by dioxiranes. N-oxides and N-oxyl radicals are not compatible because they catalyze the decomposition of the dioxirane. Oxygen insertion into Si-H bonds by dioxirane is more facile than into C-H bonds and, therefore, silanes are not compatible. Substance classes normally resistant towards dioxirane oxidation include the carboxylic acids and their derivatives (anhydrides, esters, amides, and nitriles), sulfonic acids and their de-... 

Amides of 2-iodoxybenzenesulfonic acid 495 were prepared by dioxirane oxidation of the corresponding 2-iodobenzenesulfamides 494 and isolated as stable, microcrystalline products (Scheme 2.141) [660], A single-crystal X-ray structural analysis of the alanine derivative 495 [R = (5)-CH(CH3)C02Me] showed a combination of intra- and intermolecular I--0 interactions leading to a unique tieptacoordinated iodine(V) center in this molecule [661], The analogous esters 497 were prepared similarly from the respective sulfonate esters 496 [662],... 

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>. 

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. 

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. 

On the other hand, oxidation of 161 with dimethyl dioxirane gave a 1 9 mixture of diols 165 and 166 (Scheme 31). Surprisingly and inexplicably the major product 166 results from attack on the double bond face syn to the arylsulfonyl moiety. Diol 166 could be converted to monoacetate 167 which underwent stereoselective alkylation with allyl trimethylsilane to yield 168. Similarly, acetate 167 could be converted to a single nitrile 169. Both of these transformations involve axial attack anti to the arylsulfonyl group on an intermediate N-sulfon-ium iminium ion. 

First synthesized and characterized in 1988, ° this dioxirane (TMDO) is generally prepared by oxidation of 1,1,1-trifluoroacetone with potassium monoperoxosulfate (caroate). Yellow solutions of TMDO are quite stable at 20°C. It has also been generated in homogeneous organic solutions up to 1 M by oxidation with arenesul-fonic peracids, formed in situ from the sulfonic acid, H2O2, and NaOH. ... 

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... 

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%. 

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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