And dimethyloxosulfonium

Bravo et al. studied the reaction of various ylides with monooximes of biacetyl and benzil. Dimethylsulfonium methylide and triphenylarsonium methylide gave 2-isoxazolin-5-ol and isoxazoles, with the former being the major product. Triphenylphosphonium methylide and dimethyloxosulfonium methylide gave open-chain products (Scheme 135) (70TL3223, 72G395). The cycloaddition of benzonitrile oxide to enolic compounds produced 5-ethers which could be cleaved or dehydrated (Scheme 136) (70CJC467, 72NKK1452). 

A stereoselective total synthesis of dendrobatide toxin 251 D was developed by Overman et al.237) involving an epoxidation of the (S)-proline derivative (237) to furnish the oxirane (238) as major product. In their approach towards the total synthesis of the same natural product Thomas et al.238) investigated the stereoselectivity of the epoxide formation from (S)-5-acetylpyrrolidin-2-one and dimethyloxosulfonium methylide. A diastereoselectivity of d.s. 50-60% was achieved 238. ... 

Isoflavones (388) and dimethyloxosulfonium methylide gives 2,3-dihydro-2,3-methano-4-benzopyrones with 2-vinyl-3(2H)-benzofura-nones (389) as by-products.837... 

Table 26. Reaction of N-Sulfinylimines with Dimethylsulfonium Methylide (n = 0, Reagent A) and Dimethyloxosulfonium Methylide (n = 1, Reagents B and C)...

N-Sulfinylaziridines 181 are formed as mixtures of diastereoisomers from (Ss)-179 and dimethyloxosulfonium methylide (180).38,95,96 The diastereoselectivity can... 

An interesting aspect of this reaction is the contrasting stereoselective behaviour of the dimethylsulfonium and dimethyloxosulfonium methylides in reactions with cyclic ketones (E.J. Corey, 1963 B, 1965 A C.E. Cook, 1968). The small, reactive dimethylsulfonium ylide prefers axial attack, but with the larger, less reactive oxosulfonium ylide only the thermodynamically favored equatorial addition is observed. 

Next to phosphorus ylides in importance as synthetic reagents are sulfur ylides, especially dimethylsulfonium methylide and dimethyloxosulfonium methylide. These sulfur ylides are prepared by deprotonation of the appropriate sulfonium... 

There is an important difference between the reactions of these sulfur ylides and the analogous phosphorus ylides with carbonyl compounds. Whereas phosphorus ylides react with aldehydes and ketones to yield alkenes, dimethylsulfonium methylide and dimethyloxosulfonium methylide yield epoxides. Instead of a four-center elimination in the zwitterionic intermediate, intramolecular nucleophilic displacement by oxygen occurs. 

Examples of the use of dimethylsulfonium methylide and dimethyloxosulfonium methylide in the preparation of epoxides by methylene transfer are listed in Scheme 2.11. Entries 1-4 illustrate epoxide formation with simple aldehydes and ketones. Dimethylsulfonium methylide is both more reactive and less stable than dimethyloxosulfonium methylide so it is generated and used at a lower temperature. 

Another difference between dimethylsulfonium methylide and dimethyloxo-sulfonium methylide has to do with the stereoselectivity of epoxide formation. Dimethylsulfonium methylide tends to add to ketones from the less-hindered side while dimethyloxosulfonium methylide tends to give the more stable epoxide (entries 7 and 8). It may be presumed that the stereoselectivity of epoxide formation is influenced by the reversibility of the addition step with dimethylsulfonium methylide giving the product of kinetically controlled addition and dimethyloxosulfonium ylide the product of thermodynamically controlled addition. ... 

Aldehydes and ketones can be converted to epoxides in good yields with the sulfur ylids dimethyloxosulfonium methylid (60) and dimethylsulfonium methylid (61). For most purposes, 60 is the reagent of choice, because 61 is much less... 

Methylenecyclohexane oxide has been prepared by the oxidation of methylenecyclohexane with benzonitrile-hydrogen peroxide or with peracetic acid by treatment of 1-chlorocyclo-hexylmethanol with aqueous potassium hydroxide and by the reaction of dimethylsulfonium methylide with cyclohexanone. This reaction illustrates a general method for the conversion of ketones and aldehydes into oxiranes using the methylene-transfer reagent dimethyloxosulfonium methylide. The yields of oxiranes are usually high, and the crude products, in most cases, are of sufficient purity to be used in subsequent reactions (e.g., rearrangement to aldehydes) without further purification. 

The same intermediate occurs in the Lehmann method463 for converting the methiodides of phenolic Mannich bases into 2,3-dihydrobenzo-furans, through reaction with dimethyloxosulfonium methylide. Thus, o-benzoquinone methide (207) leads to 2,3-dihydrobenzofuran according to Scheme 4. Similarly, 2-naphtholgives l,2-dihydronaphtho[2,l-6]furan through 208 and 209, formed and rearranged in situ.i6i The reaction has been applied to the synthesis of polycyclic benzofurans.483,485... 

Dimethyloxosulfonium methylide reacts with the triketone (212) to give the fused 2-hydroxymethylenedihydropyran (213) (76H(4)1755). The reaction is thought to proceed through a zwitterion and the epoxide as indicated in Scheme 41. Intramolecular nucleophilic attack leads to the dihydropyran and the overall process may be regarded as a transfer of methylene from the sulfur ylide. 

It is beneficial in terms of yield to convert an a,/3-unsaturated ketone into the cyclopropyl ketone using dimethyloxosulfonium methylide. The epoxide, formed as above, is rearranged during chromatography on silica gel. The corresponding pent-2-ene-l,5-diols are also formed, presumably through hydration of the cation, and these may be dehydrated to the pyran with p-toluenesulfonic acid (74JCS(P1)1674). 

A solution of dimethyloxosulfonium methylide in DMSO (30 ml) was prepared under argon from trimethyloxosulfonium iodide (9.6 mmol) and NaH (60% dispersion in oil, 9.6 mmol) at room temperature. After stirring for 90 min (the evolution of hydrogen ceased) the solution of the ylide was added dropwise to a solution of the vinyl sulfoxide (3.2 mmol) in DMSO (25 ml) over a 30 min period. The reaction mixture was stirred at room temperature for 14h, poured into an ice water mixture, and extracted twice with ether. The ether layers were washed twice with water, dried over anhydrous MgS04 and evaporated in vacuo to give a crude cyclopropyl sulfoxide as a white solid. Flash chromatography (silica, ethyl acetate/n-hexane (25 75) gave the (7 c,Ss) isomer (1.02g, 82%), m.p. 227-228°C and the (Sc,5s) isomer (0.17g, 14%), m.p. 202-203°C. 

Dimethyloxosulfonium methylide - known as the Corey-Chaykovsky Reagent - is a valuable alternative to dimethylsulfonium methylide and can be generated from trimethylsulfoxonium iodide. 

The ring-expansion reaction of epoxides was first reported by Okuma and coworkers, to produce less-substituted oxetanes (Scheme 7.2) [11]. The nudeophilic attack by dimethyloxosulfonium methylide is proposed to react with the less-... 

The intermediacy of such oxaspiropentanes has been proposed in the addition of diazomethane to ketonesi0) and in the reaction of dimethyloxosulfonium methylide with a-haloketones55). In contrast to phosphorous ylides, sulfur ylides usually condense with carbonyl compounds to yield epoxides, thus reaction of the N,N-dimethylaminophenyloxosulfonium cyclopropylide 99 with cyclohexanone produced the dispiroepoxide 100 which rearranged to the spiro [3.5] nonan-l-one 101 upon isolation by gas chromatography, Eq. (29) S6). 

Chloro-5,6-diphenylpyrazine (136) gave successively dimethyloxosulfonium 5,6-diphenylpyrazin-2-ylmethylide (137) [H2CS(=0)Me2, THF, N2, reflux, 5 h 93%], acetyl dimethyloxosulfonium 5,6-diphenylpyrazin-2-ylmethylide (138) (Ac20, dioxane, 0°C, 90 min 91%), and 2-acetonyl-5,6-diphenylpyrazine (139) (Raney Ni, MeOH, reflux, 30 min 60%).91... 

Like S,S-Dimethyl-N-(p-toluenesulfonyl)sulfoximine and (dimethylamino)dimethyloxosulfonium tetrafluoroborate, the 7Y-tosylsulfilimine (1) reacts as a methylene transfer reagent, converting aldehydes and ketones to epoxides (eq 3). Thus (1) is heated at 80-90 °C for 0.5 h in DMSO in the presence of Sodium Hydride, and the resulting anion is allowed to react with carbonyl compounds to give 1-mono- and 1,1-disubstituted oxiranes in 46-56% yields. ... 

Halogens (mainly chlorine) at position 4 of quinazolines 12 can be displaced by a variety of carbon nucleophiles, c.g. carbon nucleophiles derived from active methylene compounds, ketone enolates, aromatic aldehydes, organolithium reagents, alkylidenephosphorane, dimethyloxosulfonium methylide, alkynes, and cyanide. ... 

It has been found that the reaction of dimethyloxosulfonium methylide and diazomethane with (E)-3-aryl-2-phosphonoacrylates (346) using the (-)-S-phenyl-menthyl group as a chiral auxiliary gives the trans cyclopropane derivatives with high diastereoselectivity. This can be attributed to the high Jt-face differentiation of the acrylate moiety by the face-to-face interaction with the phenyl ring of the chiral auxiliary in the s-cis conformer. On the other hand, (Z)-isomers of (346) gave a mixture of cis and trans cyclopropane derivatives with low diastereoselectivity (Scheme 93). ... 

The most commonly used reagents to effect the addition of a methylene group to an aldehyde or ketone are sulfur ylides such as dimethylsulfonium methylide (1) or dimethyloxosulfonium methylide (2) (Corey-Chaykovsky reaction). This reaction is well reviewed in standard treatises of organic synthesis - and several useful monographs. - This update will concentrate on progress attained from 1975. The reader is also encouraged to consult reviews on the chemistry of the related sulfoximine-derived ylides such as (3). -"... 

A powerful class of epoxidation reagents in this category are the anions derived from A/-p-tolylsulfo-nylsulfoximines (equation 16). These reagents form epoxides directly upon addition to carbonyl compounds and are available in a number of alkyl substitution patterns. Their chemistry is similar to that of dimethyloxosulfonium methylide, to which they often provide a practical alternative due to their greater nucleophilicity. 

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