Sulfonium salts, from thioethers

Without additional reagents Thioethers from sulfonium salts... 

Scheme 10 Generation of sulfonium salts from thioethers.

Arylmethyl(homobenzyl)ethylsulfonium salts are appropriate substrates for Suzuki-type coupling reactions. In this reaction, performed on a polymer-bound sulfonium tetrafluoroborate, the benzyl fragment on the sulfur atom was transferred to the boronic acid residue. The sulfonium salt was prepared from an al-kylthiol resin by alkylation with a substituted benzyl halide to give thioether 98 and subsequent alkylation with triethyloxonium tetrafluoroborate. Reaction with a boronic acid derivative yielded diaryl methanes 99 [94] (Scheme 6.1.22). 

The alkylidenecarbene generated from alkenyl(phenyl)iodonium tetrafluoroborate by base adds irreversibly to THT to form a sulfonium ylide, which further gives the sulfonium salt along with a small amount of a thioether (Scheme 40). This was in contrast to the corresponding oxonium ylide where the reaction was found to be reversible <1996JA10141>. 

Inversion at Co —SR R is fast (0.1-10s ) but diastereoisomeric systems have been detected by H and C NMR spectroscopy. Thus (305) shows clearly resolved signals of the tren ligand arising from the chiral thioether. " Also the related t-(N,S)[Co (R)cys (tren)] chelate shows immediate H-NMR spectral changes on deprotonation of the dangling equatorial carboxylate arising from rapid (< 5 s) mutarotation of the (/ )S(J )C, (5)S(Ji)C diastereoisomeric mixture. Thus inversion appears to be 10 -10 times more rapid than for uncoordinated sulfonium salts, a result in keeping with other M—SR R systems. ... 

It should be noted that the sulfur atom in methionine sulfoxide is a new chiral center, hence a pair of diastereosimers is present in the intermediates. This is a minor complication that is absent from an alternative method for the masking of the thioether its more recently proposed conversion to a tert.sulfonium salt by the reaction of an activated N-acyl derivative of the amino acid with methyl p-toluenesulfonate ... 

This side reaction is reversible. As already mentioned in connection with the protection of the methionine side chain (Chapter VI) the thioether can be regenerated from the ternary sulfonium salts by treatment with mercaptanes under mildly basic conditions. Nevertheless, this long overlooked alkylation should serve as warning against the indiscriminate use of scavangers. The more acid stable thioanisole or the equally efficient 4-methylthiophenol are less likely to cause similar problems. 

As already noted above, thiols, produced by nucelophiUc substitution or from organometallic reagents, can be converted to thioethers by a second nucleophilic substitution reaction.These sulfides, on alkylation,produce sulfonium salts (Equation 8.65), which can be used or further alkylation reactions (e.g., see SAM Figure 8.24). 

Trialkyloxonium fluoroborates Sulfonium salts from cyclic thioethers R,0 BFf Cs -> Cs ... 

Trialkyloxonium fluoroborates Sulfonium salts from cyclic thioethers Penicillin derivs. 

Synthesis of macrocycle 311 Thioether 309 (1.0 equiv), immo-bihzed on AtgoGel, was suspended in DCM and treated with MeOTf (10.0 equiv) at room temperature for 1 hour to generate resin-bound sulfonium salt 310, which was purified by filtration and washings. Sulfonium salt 310 was resuspended in DCM and treated with DBU (10.0 equiv). The reaction was shaken at room temperature for 22 hours to generate the stabilized sulfur ylide, which imderwent cyclative cleavage, to yield macrocyclic lactone ( )-311 in good yield (52% from 309, 31% after flash chromatography) and purity exclusively as the treats diastereoisomer. 

S-Alkylatlon. Methyl iodide alkylates thioalkoxides and sulfides to produce sulfides and sulfonium ions, respectively. For example, thioalkoxides produced from thiocarbonyl compounds are methylated with methyl iodide to generate the corresponding methyl thioether (eq 22). Sulfonium halides, derived from the reaction of methyl iodide with an alkyl sulfide, are sometimes labile in solution and may undergo further reaction (eq 23). Dimethyl Sulfoxide when refluxed with an excess of methyl iodide produces trimethyloxosulfonium iodide, which is collected as a white solid and recrystallized from water. Similarly, methylation of Dimethyl Sulfide produces trimethylsulfonium iodide. Treatment of trimethyloxosulfonium and trimethylsulfonium salts... 

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