Sulfonium betaines

We classify these compounds according to their degree of unsaturation. There is a class of eight tt-electron systems containing two O, S or NR atoms in the ring which possess significant stability. We then consider the thiabenzenes, which behave as cyclic sulfonium betaines, and related compounds. 

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. 

Rearrangement of sulfonium betaines s. 17, 392 Mercuric bromide S N-Transglycosidation... 

Stereoselective epoxidation can be realized through either substrate-controlled (e.g. 35 —> 36) or reagent-controlled approaches. A classic example is the epoxidation of 4-t-butylcyclohexanone. When sulfonium ylide 2 was utilized, the more reactive ylide irreversibly attacked the carbonyl from the axial direction to offer predominantly epoxide 37. When the less reactive sulfoxonium ylide 1 was used, the nucleophilic addition to the carbonyl was reversible, giving rise to the thermodynamically more stable, equatorially coupled betaine, which subsequently eliminated to deliver epoxide 38. Thus, stereoselective epoxidation was achieved from different mechanistic pathways taken by different sulfur ylides. In another case, reaction of aldehyde 38 with sulfonium ylide 2 only gave moderate stereoselectivity (41 40 = 1.5/1), whereas employment of sulfoxonium ylide 1 led to a ratio of 41 40 = 13/1. The best stereoselectivity was accomplished using aminosulfoxonium ylide 25, leading to a ratio of 41 40 = 30/1. For ketone 42, a complete reversal of stereochemistry was observed when it was treated with sulfoxonium ylide 1 and sulfonium ylide 2, respectively. ... 

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 ring expansion reaction of diaryl cyclopropenones and cyclopropene thiones occurring with pyridinium, sulfonium, and phosphonium enolate betaine 427268-270) is related to 1,3-dipolar cycloadditions. This process results in formation of 2-pyrones 428 by loss of pyridine (or sulfide or phosphine) and insertion of the remaining fragment C=C-0 to the C1(2)/C3 bond of the cyclopropenone ... 

Likewise, pyridinium and sulfonium enolate betaines 427 react with 4,4-diacyl triafulvenes to give ring expansion to the six-membered ring of 2-diacylmethylene pyrane 560269) ... 

With reference back to Scheme 3, the substituent G in these reactions is most commonly an onium group bearing a positive charge. Examples are sulfonium and phosphonium groups. The intermediates (7) are thus various types of ylides, and the adducts (8) are defined as being betaines. 

Stabilized sulfonium ylides react with cyclopentenone to give the corresponding cyclopropane with high diastereoselectivity as a result of base- or ylide-mediated (g) equilibration of the intermediate betaine.38 When using chiral sulfonium ylides, betaine equilibration compromises enantioselectivity, because whereas one diastereomer ring closes rapidly, the other diastereomer undergoes epimerization at the ester stereocentre, ultimately leading to the opposite enantiomer of the cyclopropane. 

A two-step mechanism (Scheme 3.34) for epoxidation was proposed in which intermediate betaine A and B are obtained from the carbonyl compound and sulfonium ylides irreversibly and from aminosulfoxonium ylide reversibly (step 1). Betaine (A or B) then undergoes ring closure (step 2) irreversibly. 

A betaine intermediate is formed, the fragmentation of which leads to formation of an oxirane ring by intramolecular substitution by the anionic oxygen (Eq. 89). The sulfonium ylides also react with other types of compounds containing an electrophilic unsaturated bond (C=C, C=N), giving cyclopropane derivatives and aziridines. 

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. 

The substitution of sulfur for the nitrogen of choline and betaine ester (sulfonium compounds), greatly increases the nicotinic actions in some cases. The addition of oxygen to the sulfur (sulfonyl compounds) greatly diminishes the potency (6). 

First a Michael addition of the pyridinium ylide to cyclopropenone occurs. This is followed by a reorganization of the intermediate 33 with pyridine elimination giving the keto ketene 34, which by ring closure yields the 2//-pyran-2-one system. Sulfonium and phosphonium ylides can be used instead of pyridinium enol betaines. 

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

Methionine differs from the other methyl donors in being a simple thioether, whereas the others are sulfonium compounds or quarternary ammonium compounds. Onium compounds with an anionic group appear to be the only methyl donors choline, an onium compound, is inert as a donor until it is oxidized to betaine. Methionine was found to transfer its methyl group only in the presence of ATP. Cantoni has... 

The steps before the ring-closure and simultaneous ehmination of sulfide are supposed to be reversible. The steric and electronic effect will influence the reversibility to some extent. The bond rotation step to form a perpendicular arrangement of the sulfonium cation and amide anion in the betaine intermediate is a key step to account for the stereochemical outcome. 

H-benzotriazole 1003 0-benzoyl esters 134 benzoyl hydrazones 440 N-benzoyl hydrazones 394 benzoyl peroxide 72 benzoylmethyl sulfonium ylides 1115 benzyl bromide 545 0-benzyl hydroxyacetone 705 N-benzyl ketimines 958 benzyl protecting groups 558 benzyl thiols 52 a-benzylation 1184 -aldehydes 1184 0-benzylhydroxyamines 1003 benzylideneacetone 591 benzylthiol 257 betaines 257... 

Blunden, G., Smith, B.E., Irons, M.W, Yang, M.H., Roch, O.G., Olive, G.P., and Asmita, V. (1992) Betaines and tertiary sulfonium compounds from 62 species of marine algae. Biochem. Syst. Ecol., 20, 373-388. 

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