Sulfides nucleophile oxidation

Nucleophilic reactivity of exocyclic sulfur appears in acidic medium. 2-AryI thiazolyl sulfones are obtained from the corresponding sulfides by oxidation with HjO- in HOAc at 100°C (272). The same oxidation takes place with alkyl sulfides (203. 214, 273-275) and dithiazolylsulfides (129). However, the same reaction with 2-benzylthio derivatives gives benzylal-cohol and the related A-4-thiazoline-2-thione (169). 

The final method for constructing epidithiodiketopiperazine motifs relied on the nucleophilic thiolation of /V-acyliminium ions. Access to alpha-oxidized diketopi-perazine structures was central to this approach, and key developments were made in this regard. Schmidt first demonstrated the feasibility of this ionization approach in 1973 by conversion of proline anhydride to its diacetate using Pb(OAc)4 [42], Hydrolysis of the acetates, ionization of the hemiaminals with zinc chloride in the presence of hydrogen sulfide, and oxidation with iodine provided the epidisulfide of interest. In 1975, Matsunari reported access to alpha-methoxy diketopiperazines,... 

The oxidation of sulfides to sulfoxides (1 eq. of oxidant) and sulfones (2 eq. of oxidant) is possible in the absence of a catalyst by employing the perhydrate prepared from hexafluoroacetone or 2-hydroperoxy-l,l,l-trifluoropropan-2-ol as reported by Ganeshpure and Adam (Scheme 99 f°. The reaction is highly chemoselective and sulfoxidation occurs in the presence of double bonds and amine functions, which were not oxidized. With one equivalent of the a-hydroxyhydroperoxide, diphenyl sulfide was selectively transformed to the sulfoxide in quantitative yield and with two equivalents of oxidant the corresponding sulfone was quantitatively obtained. 2-Hydroperoxy-l,l,l-fluoropropan-2-ol as an electrophilic oxidant oxidizes thianthrene-5-oxide almost exclusively to the corresponding cw-disulfoxide, although low conversions were observed (15%) (Scheme 99). Deprotonation of this oxidant with sodium carbonate in methanol leads to a peroxo anion, which is a nucleophilic oxidant and oxidizes thianthrene-5-oxide preferentially to the sulfone. 

Oxidation of a sulfide to sulfoxide is known to be an electrophilic reaction, in contrast with nucleophilic oxidation of sulfoxide to sulfone. Since 2-nitrobenzenesulhnyl ehloride/K02 oxidizes sulfides to sulfoxides selectively, intermediate 48 must be the actual active intermediate. Moreover, in the presence of l,4-diazabicyclo[2.2.2.]octane (DABCO), which is a radical capturing reagent, the oxidation of methyl phenyl sulfide to the sulfoxide was inhibited. In order to further detect the intermediate 48, pure 5,5-dimethyl-1-pyrroline-l-oxide (DMPO) was used as a trapping reagent and spin adduct was obtained223. The ESR spectrum of the DMPO spin adduct was obtained by the reaction of 02 with 2-nitrobenzenesulfinyl chloride (hyperfine coupling constants, aH = 10.0 G and aN = 12.8 G). 

A similar in situ generation of a sulfide nucleophile can be accomplished by the reaction of an allylic carbonate with a Pd° catalyst and PhSSiMe3. Following oxidative addition by the Pd° into the allylic C—O bond to form the ir-allyl complex, CO2 is lost from the carbonate counterion, generating... 

The mechanism of oxygen transfer from oxaziridines to nucleophiles is believed to involve an Sn2 type reaction and this assumption is supported by theoretical and experimental studies. When sulfides are oxidized to the corresponding sulfoxides and sulfones, the molecular recognition is steric in origin, and it is determined by the substituents on both the substrate and the oxaziridine. For the oxidation of enolates, the molecular recognition is explained with an Sn2 mechanism as well as by an open (non-chelated) transition state where the nonbonded interactions are minimized. The mechanism of oxygen transfer to an enolate to form the corresponding acyloin is shown below. ... 

It is plausible that the first steps in the mechanism of the Corey-Kim oxidation involve the initial Sn2 reaction between the sulfide nucleophile and the NCS that bears the electrophilic chlorine to form an intermediate sulfonium chloride species and a succinimide anion that in turn attacks the newly formed electrophilic sulfonium to yield... 

Although thiols are generally stronger nucleophiles than alcohols and amines, the sensitivity of sulfides towards oxidation as well as the formation of disulfide made the cross-coupling between aryl halides and thiols difficult. From all previously reported results, it was foimd that only aryl iodides were suitable for this copper-catalyzed coupling process. 

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. 

Moving one column to the left in the periodic table, sulfide nucleophiles are more reactive than the analogous oxide systems, and, as other experiments have shown, their selenium counterparts are even more reactive. Thus, this column exhibits the same trend as that observed for the hahdes. The phenomenon is general for other columns in the periodic table. 

In another process for the synthesis of PPS, as well as other poly(arylene sulfide)s and poly(arylene oxide)s, a pentamethylcyclopentadienylmthenium(I) TT-complex is used to activate -dichlorobenzene toward displacement by a variety of nucleophilic comonomers (92). Important facets of this approach, which allow the polymerization to proceed under mild conditions, are the tremendous activation afforded by the TT-coordinated transition-metal group and the improved solubiUty of the resultant organometaUic derivative of PPS. Decomplexation of the organometaUic derivative polymers may, however, be compHcated by precipitation of the polymer after partial decomplexation. 

In the alcohol oxidations, the sulfonium intermediate (2, nucleophile = R2C(OH)) loses a proton and dimethyl sulfide to give the carbonyl compound (42). The most common mechanism for the decomposition of (2) is attack by a mild base to remove a proton from one of the methyl groups. Subsequent cycHc coUapse leads to the carbonyl compound and dimethyl sulfide (eq. 9) ... 

Thiirane 1-oxide undergoes acid-catalyzed ring opening by ethanethiol to give ethyl 2-ethylthioethyl disulfide. Treatment of thiirane 1,1-dioxide with thiolate anions, sodium sulfide or thiourea gives /3-mercaptosulfinic acid derivatives (75S55). Thiiranium ions are attacked at carbon by most sulfur nucleophiles (79ACR282), but see Section 5.06.3.4.3 for exceptions. 

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

Thiols, the sulfur analogs of alcohols, are usually prepared by Sjv 2 reaction of an alkyl halide with thiourea. Mild oxidation of a thiol yields a disulfide, and mild reduction of a disulfide gives back the thiol. Sulfides, the sulfur analogs of ethers, are prepared by an Sk2 reaction between a thiolate anion and a primary or secondary alkyl halide. Sulfides are much more nucleophilic than ethers and can be oxidized to sulfoxides and to sulfones. Sulfides can also be alkylated by reaction with a primary alkyl halide to yield sulfonium ions. 

In the oxidative Eschenmoser sulfide contraction (Scheme 11), thioamide 59 is oxidized by benzoyl peroxide to give either a symmetrical disulfide or the O-benzoate of the thiolactam-S-oxide. In any event, the once-nucleophilic thioamide sulfur atom is now forced to adopt the role of electrophile a reactivity umpolung has, in effect, been achieved.13 The nucleophilic enamide 65 attacks the sulfur atom leading to the formation of sulfur-bridged intermediate 66. The action of a phosphine or a phosphite thiophile on the putative episulfide then gives vinylogous amidine 67. 

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