Thioethers cleavage, reductive

Sulfur analogs, 2-tetrahydrofuranyl and 2-tetrahydropyranyl thioethers, were reduced by alone to alkyl 4- or alkyl 5-hydroxyalkyl thioethers resulting from the preferential reductive cleavage of the carbon-oxygen (rather than the carbon-sulfur) bond. Thus refluxing for 2 hours with alane in ether converted 2-alkylthiotetrahydrofurans to alkyl 4-hydroxybutyl thioethers in 63-72% yields, and 2-alkylthiotetrahydropyrans to alkyl 5-hydroxypentyl thioethers in 58-82% yields [794]. 

His group [312,313] has done important work on the reductive cleavage of the C-S bonds of phenyl thioethers. These workers have shown the potential of two radical anions lithium p,p -di-t-butylbiphenylide (LDBB) and lithium l-(dimethylamino)naphthalenide (LDMAN) as reducing species. 

The following discussion will be focused on the effect of structural variations on the kinetics of fragmentation, the cleavage mode, and the stepwise or concerted nature of the process. Similar concepts have also been applied to the reductive cleavage reactions of other series of substrates, i.e. a-substituted acetophenones [246-250], perbenzoates [240, 251], peroxides [242, 252-256], sulfides [244, 257, 258], sulfonium salts [259-263], nitrocumenes [264, 265], arylmethyl aryl ethers and thioethers [266-270]. 

Dealkylation of alkyl cobalt species by thiolate was suggested as a reductive cleavage process, involving reduction of alkylcobalamin with thiol to form a trans axial thiol complex . This accounts for the low yield of thioether . Carbon-13 and P studies... 

Reductive cleavage of thioethers and sulfones Mercaptans and hydrocarbons from thioethers Sulfinic acids and hydrocarbons from sulfones Extractor technique... 

Analogous to the preparation of [ C]methyl ethers is the reaction of alkali thiolates with [ CJmethyl iodide to give the labeled thioethers. The synthesis of (5)-[methyl- C]-methionine (201), the most important representative of this substance class, may serve as an example i . It is conveniently available in 60-80% radiochemical yield by reaction of [ CJmethyl iodide with deprotonated (5)-homocysteine, generated in situ by reductive cleavage of the 5-benzyl. It is widely used as a [ C]methyl donor in fermentative labeling processes (see Chapter 12). 

The development of sulfone linkers, the exploration of sulfone based chemical transformations and cleavage strategies are an important objective in soHd-phase organic synthesis. This kind of Hnker (Tab. 3.7) has been used with thioethers [108], sulfoxides [109], sulfones [110], sulfonic acids and their corresponding derivatives [111]. Because carbon-sulfur bonds can be cleaved under very mild conditions, some Hnkers have been based on this effect. They can be cleaved under reductive conditions ]112, 113], photolytic conditions [114, 115] or with strong bases [116]. Various safety catch Hnkers have been developed based on the fact that thiols can be oxidized to sulfoxides and sulfones [112, 113]. 

An unusual reaction pattern has been found for the electrochemical and chemical (by ascorbic acid) reduction of the rhenium(II) thioether complex [Re(9S3)2] " (9S3 = 1,4,7-trithiacyclono-nane). Instead of the formation of the corresponding rhenium(I) complex, C bond cleavage and the release of ethene was observed and the brown rhenium(III) species [Re(9S3)(SC2H4SC2H4S)]" (250) was isolated as a BF4 salt. Lfpon electrochemical reduction of [Re(9S3)(SC2H4SC2H4S)]" further loss of ethene was observed while the analogous technetium complex can be reversibly reduced to [Tc(9S3)(SC2H4SC2H4S)]. 

Screttas and Micha-Screttas synthesized various dilithiated alkyls by the method of reductive sulphur-carbon bond cleavage with metallic lithium. The example of compound 147 shows that thioethers 146 are cleaved selectively in the presence of ether functionalities (Scheme 53). ... 

Botta and coworkers recently developed an Oxone cleavage methodology for the solid-phase synthesis of substituted uracUs (equation 57) . Whereas some common methods of thioether cleavage, such as reduction with Na/NHs, acid catalyzed hydrolysis, heavy metal ions followed by treatment with hydrogen sulfide and iodofrimethylsilane proved to be unsuccessful for this reduction, Oxone was shown to be an efficient and selective reagent for cleavage of polymer bound thiouracUs. 

Sulfonium salts of thiepanes are readily formed by electrophilic attack of alkyl halides on the cyclic thioether. Thus, thiepane (35) was found to yield a sulfonium iodide (123), which at elevated temperatures and in the presence of excess methyl iodide underwent ring cleavage to yield 1,6-diiodohexane (isolated as the 1,6-diphenoxy derivative Scheme 24) (53M1206). The alkoxysulfonium salt (124) formed by reaction of (35) with t-butyl hypochlorite (equation 23) was characterized as a stable hexachloroantimonate (67JOC2014). Reduction of thiepane 1-oxide (115) to thiepane has been achieved using an aqueous solution of NaHSC>3 (72JOC919). A hydroxysulfonium salt intermediate (125) has been proposed in the latter reduction reaction which provides a general method for sulfoxide reductions under mild conditions (equation 24). 

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