Sulfonium salts nucleophilic substitution

A naturally occurring sulfonium salt S adenosylmethionme (SAM) is a key sub stance in certain biological processes It is formed by a nucleophilic substitution m which the sulfur atom of methionine attacks the primary carbon of adenosine triphosphate dis placing the triphosphate leaving group as shown m Figure 16 7... 

In an earlier study the authors proposed a [3.2.0] bicyclic sulfonium salt 8 as the reactive intermediate in the trimethylsilyl iodide mediated ring contraction of 4-methoxythiephane <1996T5989>. Enantiomerically pure thio-lane derivatives were synthesized via a ring contraction of a seven-membered sulfur heterocycle by nucleophilic transannular substitution <2000TA1389>. The thiepane derivative 15, derived from d-sorbitol, was converted into the dimesyl derivative 16 following deprotection under acidic conditions. Treatment of 16 with sodium azide in DMSO at 120°C yielded the corresponding thiolane as a mixture of two diastereoisomers, 17a and 17b, in a 5 1 ratio (see Scheme 1). 

Nucleophilic substitution at the a-carbon atom does not occur in the case of the most studied and stable bicyclic disulfonium dications.96 Although the reaction of dication 34 with bromide ions formally leads to the S C bond cleavage, the reaction mechanism involves initial nucleophilic attack at the sulfonium atom by the bromide anion. The bromosulfonium salt intermediate... 

Placing anion stabilizing groups on the cyclopropane greatly facilitates generation of cyclopropyl nucleophiles. The diphenylsulfonium ylide has proven to be an exceptionally versatile conjunctive reagent25). The sulfonium salt 9, available from either 3-chloro-l-iodopropane (Eq. 24a) or 3-chloro-l-propanol (Eq. 24b), is a nicely crystalline stable salt that can be stored indefinitely26,Z7). While substituted... 

Homofamesyl iodide 7 was prepared by the reaction sequence shown in the margin. Of interest here is the two-step transformation of an alkyl halide into a Crextended alkyl halide.9 Compound 30 is first subjected to a nucleophilic substitution by an urganolithium species with formation of a homoallylic phenyl thioether This is then methylated in a second step to an intermediate sulfonium salt. The final SN2 reaction with an iodide ion releases thioanisol as a stable leaving group to give compound 7. 

Moreover, product formation was not the same. Dibenzyl ethylsulfonium salt 72 gave only benzyl ethyl sulfide (73) and benzyl thiocyanate 74, but no dibenzyl sulfide or ethyl thiocyanate. By contrast, the cyclic sulfonium salt 75 gave a mixture containing chiefly (80%) dihydroisothianaphthene (76) with an equivalent amount of ethyl thiocyanate (77) and a minor amount (20%) of the sulfide-thiocyanate 78. This work represents the first direct experimental information on the rate of bimolecular nucleophilic substitution and relative orientation of the benzene ring and the leaving group and it demonstrates clearly the importance of stereoelectronic effects in these reactions. 

An intramolecular nucleophilic substitution of the dimethyl sulfide group by a cathodically generated radical anion is postulated in the formation of the in-dane derivative 133 from the sulfonium salt 134 (Eq. (203)). 

Indium-mediated allylation of a nitro group is achieved in aqueous media to give A,A-diallylamine and 7V,0-diallylhydroxylamine (Equation (81)) 316 In situ generated sulfonium salts derived from a,/3-enones undergo a nucleophilic substitution with allylindium reagents to give the corresponding Michael addition products (Scheme 83).317... 

Sulfonium salts are electrophiles nucleophilic substitution displaces a neutral sulfide leaving group... 

Sulfonium salts react in several ways. They may behave as a leaving group, undergoing substitution by a nucleophile or fragmenting with the formation of an alkene. However, the most important reaction of sulfonium salts involves the formation of an ylide in the presence of a base. The carbanion of this sulfur ylide is stabilized by the adjacent positively charged sulfonium ion. The reaction of the carbanion with a carbonyl group parallels that of a phosphonium ylide in the Wittig reaction. However, the decomposition of the intermediate dipolar species is different and leads to the formation of an epoxide (oxirane) rather than an alkene. 

Warming the sulfonium salt (5) may cause elimination of a p-hydrogen to yield a mixture of the sulfide and the alkene, i.e. route (iv) in Scheme 3. On the other hand, proton abstraction from (5) by treatment with a strong base gives the sulfur ylide (6) which can undergo molecular rearrangement to form the sulfide (7). Sulfonium salts are unstable in basic media as a result of their tendency to undergo nucleophilic substitution reactions. 

A useful variant of the Darzens reaction has been reported for the preparation of fosfomycin from diethyl chloromethylphosphonate. Nucleophilic substitution of chlorine in diethyl chloromethylphosphonate with dimethyl sulfide gives the sulfonium salt, further converted into its stable ylide by the use of NaH in DMSO. The addition of the ylide to acetaldehyde produces diethyl 1,2-epoxypropylphosphonate, thus avoiding the problems associated with the stability of chloromethylphosphonate carbanions (Scheme 4.4). 

Tricoordinated sulfur compounds, such as sulfoxides, sulfonium salts, and related derivatives, undergo nucleophilic substitution upon treatment with nucleophiles, and are useful for investigation of the mechanism at the reactions... 

Related cyclopropanations have also been reported using sulfonium and telluronium ylides as intermediates. In particular, the cyclopropanation of enones has been carried out employing an allyl bromide as the cyclopropa-nating reagent and sulfonium and telluronium salts 134 and 135 as pre-catalysts (Scheme 7.84). These species, in the presence of a base, generated the corresponding ylide which underwent the cascade Michael/intramolecular nucleophilic substitution and it is in this second step that the real catalytically active species is released, able to interact with another molecule of the allyl bromide and thus regenerating the sulfonium or telluronium salts pre-catalysts, which can afterwards continue in the catalytic cycle. The substitution at the... 

On the other hand, cleavage of the bond is facile in nucleophilic substitutions involving sulfonium salts and the leaving ability of the dial-kylsulfide group compares with that of a bromide ion. As a result, there are several examples of type B substitutions in the literature. 

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