Aryl thiols, methylation, synthesis

Methylation of aryl thiols. PTC methylation of l C-aryl thiols with methyl Iodide (2 ) Is very useful for microscale synthesis of C-labeled aryl methyl sulfides (2j ). The reaction, using tetrabutylammonlum hydrogensulfate as catalyst and sodium hydroxide as base In methylene chloride and water, proceeds at ambient temperature In 50-100Z yield. 

A one-pot synthesis of a series of 1,2-trans-related methyl 1-thio-glycopyranoside peracetates involves acetobromlnation followed by treatment with the methanethiolate anion. Since this latter step causes some de-esterlflcation, the products were reacetylated. Fusion of penta- -acetyl-3-D-glucopyranose or its 2-amlno analogue with aryl thiols in the presence of zinc chloride affords the 3-... 

DCC can be used to prepare 5-alkyl and 5-aryl thiocarboxylates (1) from carboxylic acids and thiols according to equation (5). This method has been successfully applied to the synAesis of thiol esters with sensitive substituents, e.g. 5-methyl thioacrylate, a natural product. In particular, N-protected amino acid and peptide 5-phenyl esters, which are useful building blocks in peptide synthesis, are obtained in excellent yields without racemization. N-Hydroxyphthalimide and DMAP have been used as cocatalysts to facilitate the reaction. The preparation of the Wittig reagent (5) by this route is shown in equation (6). 

In comparison to amines and thiols, alcohols are much less nucleophilic. Consequently, the reductive elimination process to form the C—O bond [91b, 92] is much slower than the analogous processes that form C—N and C—S bonds [89]. In 1996, Palucki et al. described the first intiamolecular Pd-catalyzed synthesis of cyclic aryl ethers from o-haloaryl-substituted alcohols [93]. For example, 3-(2-bromophenyl)-2-methyl-2-butanol (91) was converted to 2,2-dimethylchroman (92) under the agency of catalytic Pd(OAc)2 in the presence (.V)-(-)-2,2 -bis(di-/ -tolylphosphino)-l,T-binaphthyl (Tol-BINAP) as the ligand and K,CO, as the base. The catalysts originally employed in this method worked well for the tertiary alcohols, and moderately well for cyclic secondary alcohols, but not for acyclic secondary alcohols. However, the use of new, di-zert-butylphosphinobiaryl ligands has significantly expanded the scope of this process [94]. 

Synthesis of these simple type of thiol derivatives will be Just briefly discussed here because comprehensive reviews on thiols and their derivatives are available (2, 21 ). The methyl sulfide compounds are most readily obtained by methylation of the corresponding thiol. Nucleophilic substitutions with methane thlolate on alkyl halides and occasionally with aryl halides lead directly to the methyl sulfide product. The syntheses of methyl sulfide and sulfone metabolites of xenoblotlca are summarized In Table IX. 

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