Thioethers cleavage

Na/NH3, >54% yield. Methyl thioether cleavage of BOC-protected methionine. ... 

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. 

Thioether cleavage of 68a with aluminum bromide in benzene112 or ethereal hydrogen chloride 285 affords 2-aminobenzo[6]thiophene in high yield. Similar cleavage of 68b and 68c gives 2-amino-3-methyl-benzo[6]thiophene and the imine (14), respectively.113... 

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. 

Silyl-derived protective groups are also used to mask the thiol function. A complete compilation is not given here since silyl derivatives are described in the section on alcohol protection. The formation and cleavage of silyl thioethers proceed analogously to simple alcohols. The Si—S bond is weaker than the Si—O bond, and therefore sulfur derivatives are more susceptible to hydrolysis. For the most part silyl ethers are rarely used to protect the thiol function because of their instability. Silyl ethers have been used for in situ protection of the — SH group during amide formation. ... 

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. ... 

Surprisingly there are relatively few data on the cathodic or anodic behaviour of sulfoxides 77. It is quite interesting to consider that the sulphoxide function is intermediate between the corresponding thioether and sulphone. Thus data concerning the cathodic properties of sulphoxides derive both from the basicity of the S=0 group and from their capability to allow the formation of the corresponding thioether, while cleavage reactions on the C—S bond are quite unusual. On the other hand, oxidation may provide sulphones. 

A variety of cleavage conditions have been reported for the release of amines from a solid support. Triazene linker 52 prepared from Merrifield resin in three steps was used for the solid-phase synthesis of aliphatic amines (Scheme 22) [61]. The triazenes were stable to basic conditions and the amino products were released in high yields upon treatment with mild acids. Alternatively, base labile linker 53 synthesized from a-bromo-p-toluic acid in two steps was used to anchor amino functions (Scheme 23) [62]. Cleavage was accomplished by oxidation of the thioether to the sulfone with m-chloroperbenzoic acid followed by 13-elimination with a 10% solution of NH4OH in 2,2,2-trifluoroethanol. A linker based on l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) primary amine protecting group was developed for attaching amino functions (Scheme 24) [65]. Linker 54 was stable to both acidic and basic conditions and the final products were cleaved from the resin by treatment with hydrazine or transamination with ra-propylamine. 

The deprotection of the polyamine-thioethers 40a,b can also be accomplished in similar good yields with Li/naphthalene in THF (214). Cleavage of the thioether functions also commenced with [PdCl2(NCMe)2] in the case of 40b (216), and it is likely that the other macrobicycles will also undergo this metal-ion mediated cleavage reaction as well (Scheme 2). Note that this reaction cleaves only one of the two thioether bonds forming a macrocyclic ligand with one thiophenolate and one vinyl-thioether moiety, as... 

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