Electrophiles thioethers

Electrochemical reduction of disulfides Reaction with electrophiles Thioethers from halides... 

It is noteworthy that some catalysts convert thioethers to quaternary salts where the reactive electrophilic center is no longer one of the two C centers but the C sp center of the thiazolium salt (284. 285). Thus... 

The classical structures of pyrrole, furan and thiophene (31) suggest that these compounds might show chemical reactions similar to those of amines, ethers and thioethers (32) respectively. On this basis, the initial attack of the electrophile would be expected to take place at the heteroatom and lead to products such as quaternary ammonium and oxonium salts, sulfoxides and sulfones. Products of this type from the heteroaromatic compounds under consideration are relatively rare. 

These compounds typically react with electrophiles on carbon and in this respect they resemble enamines, enol ethers and enol thioethers. For example, both pyrrole and 1-pyrrolidinocyclohexene can be C-acetylated (Scheme 4). 

In an attempt to protect thiophenols during electrophilic substitution reactions on the aromatic ring, the three substituted thioethers were prepared. After acetylation... 

An 5-l-/w-nitrophenyl-2-benzoylethyl thioether was used to protect thiophenols -during electrophilic substitution reactions of the benzene ring. ... 

In an attempt to protect thiophenols during electrophilic substitution reactions on the aromatic ring, the three substituted thioethers were prepared. After acetylation of the aromatic ring (with moderate yields), the protective group was converted to the disulfide in moderate yields, 50-60%, by oxidation with hydrogen peroxide/boiling mineral acid, nitric acid, or acidic potassium permanganate. ... 

Two-component methods represent the most widely applied principles in sulfone syntheses, including C—S bond formation between carbon and RSOz species of nucleophilic, radical or electrophilic character as well as oxidations of thioethers or sulfoxides, and cheletropic reactions of sulfur dioxide. Three-component methods use sulfur dioxide as a binding link in order to connect two carbons by a radical or polar route, or use sulfur trioxide as an electrophilic condensation agent to combine two hydrocarbon moieties by a sulfonyl bridge with elimination of water. 

The usual oxidizing agents transfer oxygen (or halogens and related species with subsequent hydrolysis) stepwise to the sulfur of thioethers Rates of step A compared with those of step B are faster with electrophilic oxidation agents (peroxy acids) inversely, rates of step B compared with those of step A are faster with nucleophilic oxidation agents (peroxy anions)339-341. 

Once again, a large amount of diverse evidence indicates the intermediacy of a vinyl cation in electrophilic additions to arylacetylenes. As in the case of the hydration of alkynyl ethers and thioethers, the vinyl cation formed is especially stable because of resonance interaction and charge delocalization with the adjacent rr center of the aromatic system. 

Cu-catalysed additions of ZnEt2 to Baylis-Hillman-derived allylic electrophiles with BINOL-based thioether ligand. 

The treatment of 2-fluorophenyl-2-iodophenyl ethers, amines, and thioethers with 3.3 equivalents of f-BuLi and further reaction with selected electrophiles gave rise to functionalized carbazoles, dibenzofurans, and dibenzothiophenes in a direct and regioselective manner. A selected example is illustrated below <06JOC6291>. Benzyl 2-halophenyl ethers was treated with f-BuLi, and then reacted with carboxylic esters to give 2,3-disubstituted benzo[t>]furans <06JOC4024>. 

Thioethers are good nucleophiles, and CH3I is an excellent electrophile. The product is Me3S+1-. 

As indicated above, the traditional base-catalysed hydrolysis of 0,5-dialkyl thio-carbonates for the synthesis of thiols is generally unsatisfactory, as oxidation leads to the formation of disulphides. Under phase-transfer conditions, the procedure produces thioethers to the virtual exclusion of the thiols, as a result of the slow release of the thiolate anions in the presence of the electrophilic ester. However, a simple modification of the reaction conditions provides an efficient one-pot reaction [50] from haloalkanes (Table 4.15) via the intermediate formation of the thermally labile (9-/ert-butyl-5-alkyl dithiocarbonates (Scheme 4.8). 

The most promising tools developed for this sort of analysis are active-site-directed irreversible inhibitors of DUBs. These inhibitors are ubiquitin or ubiquitin-like proteins chemically modified at the C-terminus by an electrophilic moiety such as a Michael acceptor or alkyl halide. The modified ubiquitin can be incubated with a purified DUB or a cell lysate containing DUB activity. Ubiquitin vinyl sul-fone (UbVS) is one such irreversible inhibitor because the vinyl sulfone moiety reacts with the active-site cysteine of the DUB, forming a thioether linkage. The covalent adduct is stable and can be detected in a variety of ways. Labeling of DUBs is specific, as only a DUB active-site cysteine will efficiently react with the vinyl sulfone moiety. 

Table 4.15. Preparation of thioethers by S-alkylation of thiols with electrophilic carbene complexes.

Interestingly, sulfonium ylides generated from electrophilic carbene complexes and sulfides can react with carbonyl compounds, imines, or acceptor-substituted alkenes to yield oxiranes [1320-1325], aziridines [1321,1326,1327] or cyclopropanes [1328,1329], respectively. In all these transformations the thioether used to form the sulfonium ylide is regenerated and so, catalytic amounts of thioether can be sufficient for complete conversion of a given carbene precursor into the... 

Transmetalation of thioethers to organocopper compounds can also be performed in some special cases. Thus, treatment of the ester 119 with Me2CuLiLiCN provides the copper reagent 120, which can be treated successfully with several electrophiles such as allyl bromide or acid chlorides to afford the expected products such as 121 (Scheme 2.54) [115, 116]. 

Dialkoxymethyllithium compounds, for example 2-lithio-l,3-dioxan (311), are generated in situ as shown in equation 69, either by reductive lithiation of a phenyl thioether with a lithium arene or by transmetallation of the corresponding trialkylstannyl compound. Subsequent quenching with electrophiles leads to the usual alkylated or functionalized species ... 

Hydroxyalkyl thioethers 134 reacted successively with n-butyllithium and lithium containing a catalytic amount of DTBB (5%), both in THF at —78°C, to form intermediates 135, which in a second step were aUowed to react with different electrophiles to yield, after hnal hydrolysis, the expected functionalized alcohols 136 (Scheme 50) " ... 

In the case of using carbon dioxide as the electrophile, seven-membered ring lactones were obtained, the reaction being exemplified with compound 405 (67% yield). On the other hand, for carbonyl compound derivatives of type 404, their cyclization under acidic conditions (85% H3PO4, toluene reflux) gave the corresponding cyclic thioethers 406 in 76-90% yield . 

Also in this case, the use of the chloro thioether 479 allowed the introduction of two different electrophiles in a sequential process. Using lithium naphthalene (the stoichiometric version of the arene-promoted lithiation) in THF at — 78°C, only a chlorine-lithium exchange occurred, so the first electrophile R R CO was introduced (—78 to —50°C). Then the second lithiation (sulfur-lithium exchange) takes place under catalytic conditions (naphthalene) and the second electrophile R R CO was introduced. After final hydrolysis, differently substituted 1,5-diols 476 were isolated (Scheme 134) °. 

On the basis of kinetic studies, a mechanism for the radical oxidation of thioether with 36 has been proposed and is indicated in Scheme D ". The key step involves the formation of a radical cation-anion pair within the solvent cage. The presence of the pic ligand in the coordination sphere of the metal reduces the electrophilicity of the peroxo complex, thus allowing the competitive radical process to take place. 

Phenolic derivatives were prepared and then converted into thioether analogs using ethanedithol followed by oxidation of this intermediate to the disulfide. Phenolic resins were prepared by electrophilic substitution of allyl phenol derivatives with formaldehyde and then flee radically copolymerizing with ethanedithol. Epoxidation was performed using epichlarohydrine. 

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