Sulfonium betaines salts

Thiabenzenes should be considered as sulfonium betaines. They react readily with acids to give mixtures of 2H- and 4/f-thiinium salts, behave as dienes with dienophiles (Equation 9), and can be oxidized to sulfoxides. The sulfimide (450) is an aza analogue of a thiabenzene and it is oxidized by KMn04 to the corresponding sulfoximide. 

The sulfur analogue of the Hauser ortho-substitution rearrangement provides access to an arylacet-ic NSAID. Reaction of the aminobenzophenone 176 with ethyl methylthioacetate and tert-butyl hypochlorite gives the intermediate 178. The reaction probably proceeds by way of formation of the S-chlorinated sulfonium derivative 177 displacement on sulfur will lead to the salt 178. Treatment with triethylamine leads initially to the betaine 179. Electrocyelic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid 180. Internal ester-amine interchange leads then to indolone 181 [45]. The thiomethyl group is then removed with Raney niekel. Saponifieation of intermediate 182 affords bromfenac (183) [46J. 

There are four main factors that affect the enantioselectivity of sulfur ylide-mediated reactions i) the lone-pair selectivity of the sulfonium salt formation, ii) the conformation of the resulting ylide, iii) the face selectivity of the ylide, and iv) betaine reversibility. 

The alkylation of the sulfide 96, the formation of the ylid 99, and the reaction with the aldehyde are all carried out in one operation. The sulfide is a good nucleophile for alkyl halides and forms the sulfonium salt 98. This gives the ylid 99 with NaOH as a convenient base in aqueous tert-butanol. The ylid selectively attacks the aldehyde to give the betaine 100 that closes to the epoxide and releases the sulfide 96 for the next round. 

P,Y-ethylene-8-sulfoniosulfonic acid betaines Sulfonium salts... 

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