Sulfur ylides alkylation

The first attempt at a catalytic asymmetric sulfur ylide epoxidation was by Fur-ukawa s group [5]. The catalytic cycle was formed by initial alkylation of a sulfide (14), followed by deprotonation of the sulfonium salt 15 to form an ylide 16 and... 

It is well known that aziridination with allylic ylides is difficult, due to the low reactivity of imines - relative to carbonyl compounds - towards ylide attack, although imines do react with highly reactive sulfur ylides such as Me2S+-CH2-. Dai and coworkers found aziridination with allylic ylides to be possible when the activated imines 22 were treated with allylic sulfonium salts 23 under phase-transfer conditions (Scheme 2.8) [15]. Although the stereoselectivities of the reaction were low, this was the first example of efficient preparation of vinylaziridines by an ylide route. Similar results were obtained with use of arsonium or telluronium salts [16]. The stereoselectivity of aziridination was improved by use of imines activated by a phosphinoyl group [17]. The same group also reported a catalytic sulfonium ylide-mediated aziridination to produce (2-phenylvinyl)aziridines, by treatment of arylsulfonylimines with cinnamyl bromide in the presence of solid K2C03 and catalytic dimethyl sulfide in MeCN [18]. Recently, the synthesis of 3-alkyl-2-vinyl-aziridines by extension of Dai s work was reported [19]. 

A -Unsubstituted 1,2,4-diazaphospholes (4) undergo A -alkylation by reaction with alkyl vinyl ether, sulfur ylides, and diazo compounds <95HAC403>. They react with acyl chlorides in a 2 1 molar ratio to give a mixture of the A -acylated diazaphosphole and the diazaphosphole hydrochloride. Preparative A -acyclation is achieved in presence of a tertiary amine. Sulfonyl chlorides and phosphorus trichloride also give A -substitution reactions (Scheme 2) <87TH 422-01 >. 

Af-Unsubstituted 1,2,4-diazaarsoles are directly alkylated by diphenyl diazomethane, diazo esters, sulfur ylides, and alkyl vinyl ethers <90TL7607, 95HAC403). 1-Alkyl-1,2,4-diazo-arsoles (12) (R = Me, CHPhj) react with dimethylsulfoxonium yhde to give bicyclic arsiranes (13) (Equation (1))... 

Some organic reactions can be accomplished by using two-layer systems in which phase-transfer catalysts play an important role (34). The phase-transfer reaction proceeds via ion pairs, and asymmetric induction is expected to emerge when chiral quaternary ammonium salts are used. The ion-pair interaction, however, is usually not strong enough to control the absolute stereochemistry of the reaction (35). Numerous trials have resulted in low or only moderate stereoselectivity, probably because of the loose orientation of the ion-paired intermediates or transition states. These reactions include, but are not limited to, carbene addition to alkenes, reaction of sulfur ylides and aldehydes, nucleophilic substitution of secondary alkyl halides, Darzens reaction, chlorination... 

Apart from their fundamental role in sulfur ylide chemistry, sulfonium salts have found applications as soft electrophiles. In alkylation of ambident nucleophiles such as the enolates of [3-dicarbonyl compounds they led to selective C-alkylation [205],... 

A limited number of other anionic species have been employed as Michael donors in tandem vicinal difunctionalizations. In a manner similar to sulfur ylides described above, phosphonium ylides can be used as cyclopropanating reagents by means of a conjugate addition-a-intramolecular alkylation sequence. Phosphonium ylides have been used with greater frequency261-263 than sulfur ylides and display little steric sensitivity.264 Phosphorus-stabilized allylic anions can display regiospecific 7-1,4-addition when used as Michael donors.265... 

Scheme 10.22 Catalytic asymmetric cyclopropanation using sulfur ylides via an alkylation/deprotonation route.

Through sulfur ylide reactions rings can be enlarged by three atoms, two from the vinyl side chain and a third one from the a-alkyl substituent of the sul-fonium ion. The reaction product is, like the starting material, a thiacycloalkane... 

A variation of the [C + C=N] pathway involves the addition of sulfur ylides to imines and this method has been effectively used to access a wide range of substituted aziridines under mild reaction conditions. Although high enantiomeric excesses can be achieved by using a chiral sulfur ylide (up to 98%), the m//rstepwise mechanism via a betaine intermediate . Sulfur ylides can be conveniently generated in situ from alkyl halides and chiral sulfides thus, benzyl bromide and tosyl imine in the presence of a camphor-derived chiral sulfide mediator provide aziridine 4 in practically quantitative yield as a 3 1 mixture of /Z-isomers and in 92% ee (A-isomer) (Scheme 8) <2001TL5451>. 

Sulfur ylides, derived from benzyl bromides and an optically active alkyl sulfide, undergo base-promoted reactions with aryl aldehydes to produce optically active 1,2-diatyl epoxides.The reaction is illustrated by equation (17) and produces epoxides with optical purities in the range of 28-47% ee. The bicyclic sulfide shown in equation (17) was derived from (-t-)-camphor8ulfonic acid and produces the (RiO-enantiomer of the epoxide in excess. 

The high tendency of a-selenoalkyllithiums, even those that bear alkyl substituents on the carbanionic center, to add at the C-1 site of enones allows the high yield synthesis of vinyl oxiranes (Schemes 132, 134 and 166). These cannot be prepared from sulfur ylides since they add across the carbon-carbon double bond of enones to produce cyclopropyl ketones (Scheme 200). ... 

Sulfur ylides are primarily synthesized by deprotonation of a sulfonium salt, which in turn is usually prepared by alkylation of a sulfrde. Branched chain sulfonium salts are not generally preparable by simple sulfrde displacement, although some can be made by other routes. - While ylide solutions are most commonly prepared and used immediately, frozen stock solutions of the more stable (2) can be stored for several months in DMSO at -20 C. ... 

Deprotonadon of thioanisole and addition of a carbonyl compound affords an isolable hydroxy sulfide which can then be alkylated (Scheme 7). Treatment with base generates the same betaine that would have been formed using the sulfur ylide approach, and effects the intramolecular displacement reaction. The addition of methylthiomethyllithium to 2-cyclohexenone exclusively provides the 1,2-addition prod-uct the dianions derived from phenylmethanethiol or allylthiol react in a similar manner. In one case a 6-keto steroidal substrate was found to undergo smooth methylenation using this procedure. 

Procedures which utilize selenides are similar, but a-lithio selenides are not generally preparable via simple deprotonation chemistry, due to facile selenium-lithium exchange. - Selenium-stabilized anions are available, however, by transmetalladon reactions of selenium acetals and add readily to carbonyl compounds. The use of branched selenium-stabilized anions has been shown to result exclusively in 1,2-addidon to unhindered cyclohexenones, in contrast to the analogous sulfur ylides. The resulting 3-hydroxy selenides undergo elimination by treatment with base after activation by alkylation or oxidation (Scheme 10). An alternative method of activating either p-hydroxy selenides or sulfides toward elimination involves treatment of a chloroform solution of the adduct with thallium ethoxide (Scheme 11). A mechanism involving the intermediacy of a selenium ylide is proposed. 

Several examples of the alkylation of sulfur ylides are known. " " This reaction is particularly useful for the synthesis of j-alkyl diphenylsulfonium salts which cannot otherwise be prepared from diphenyl sulfide, 5-alkyl iodides and silver tetrafluoroborate, since the latter reaction usually leads to a mixture of regioisomeric sulfonium salts. Diphenylsulfonium methanide on reaction with [ C]methyl iodide allows the synthesis of [ C]isopropyl diphenyl sulfonium salt which has been used for the synthesis of [ C]-2,3-epoxysqualene (Scheme 130, entry a). This reaction unfortunately is not general... 

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