Thioethers cleavage, selective

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. 

AgN03, EtOH, Pyr, 90°, 1.5 h H2S, 47% yield. An 5-triphenylmethyl thioether can be selectively cleaved in the presence of an 5-diphenylmethyl thioether by acidic hydrolysis or by heavy-metal ions. As a result of the structure of the substrate, the relative yields of cleavage by AgN03 and Hg(OAc)2 can be reversed. 

K2CO3 or CS2CO3, DMF or CH3CN, PhSH, 88-96% yield. This process is not always selective for p-nosylate cleavage. Some amines, especially cyclic ones, tend to form 4-phenyl thioethers by nitro displacement as by-products of the cleavage process. This seems to be true only for the p-nosylate. ... 

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). ... 

The above reactions in this section have been examples of addition alone or addition followed by elimination. Ligand reactions involving nucleophilic substitution are also known and these are of the dealkylation type. Lewis acids such as aluminum chloride or tin(IV) chloride have been used for many years in the selective demethylation of aromatic methyl ethers, where chelation is involved (Scheme 27). Similar cleavage of thioethers, specially using mercury(II) salts, is commonly used to remove thioacetal functions masking ketones (equation 27).104 In some cases, reactions of metal ions with thioether ligands result in isolation of complexes of the dealkylated organic moiety (equations 28 and 29).105-107... 

Uchida, K. and Stadtman, E. R. Selective cleavage of thioether linkage in protein modified with 4-hydroxynonenal. Proc. Natl. Acad. Sci. USA 89 1992a 5611-5615. 

Cleavage occurs in the tetrahydropyranyl ring or exocyclicly. The reaction is seldom useful synthetically since the two modes are competitive. In marked contrast, tetrahydropyranyl derivatives of thiols are cleaved selectively at the ring carbon-oxygen bond, giving hydroxyalkyl thioethers (58-82%) (eq 9). ... 

Stoffregen SA, Griffin AKK, Kostic NM. Thioether complexes of paHadium(II) and platinum(II) as artificial peptidases. Residue-selective peptide cleavage by a paHadiu-m(II) complex. Inorg Chem. 2005 44 8899-8907. and references therein. 

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