Ylides sulfonium

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 27. While substituted 

Related to the sulfonium salts and their ylides are the oxosulfonium salts and their ylides. Cyclopropyl (dimethylamino)phenyloxosulfonium fluoroborate 11, available by routes analogous to the preparation of 9, suffers smooth deprotonation to the corresponding ylide upon treatment with base (Eq. 26) 28). 

Entry Aldehyde or ketone Salt, method0 Oxaspiropentane° Rearrangement method13 Cyciobutanone Yietdd Ref. 

The most remarkable feature of the chemistry of these ylides is their efficient participation in typical sulfur ylide chemistry, i.e. their ability to form epoxides with carbonyl partners (Eq. 27 a)29) and spiropentanes with enones (Eq. 27 b)30). 

These reactions, which involve a normal SN2 displacement as depicted, represent the first authenticated examples of displacement with inversion of configuration at a cyclopropyl carbon27,31 . The facility of these reactions (proceeding at temperatures below 0 °C) seems even more remarkable considering the distortion that must accompany the flattening of a cyclopropyl carbon. 

If acceptor-substituted carbene complexes are generated in the presence of thioethers, ylide formation is generally the mostly favored process. The resulting sulfonium ylides are often sufficiently stable to be isolated [975,1307-1309]. Typical reactions of sulfonium ylides include 1,2-alkyl migration, leading to products of 

In reactions involving sulfonium ylides fewer side-reactions than with oxonium ylides are usually observed. This is probably because of the stabilization of the former by dtt-pK interaction this is not possible with oxonium ylides. 

In addition to 1,2-alkyl shifts, sulfonium ylides with P-hydrogen can also undergo fragmentation into an olefin and a thioether [1317,1318]. When allylic thioethers are treated with two equivalents of ethyl diazoacetate in the presence of a catalyst for diazodecomposition, S-alkylation and elimination of the thioalkyl group from the initially formed a-alkylthio-4-alkenoic esters occurs to yield 2,4-dienoic esters [1319]. 

Interestingly, sulfonium ylides generated from electrophilic carbene complexes and sulfides can react with carbonyl compounds, imines, or acceptor-substituted alkenes to yield oxiranes [1320-1325], aziridines [1321,1326,1327] or cyclopropanes [1328,1329], respectively. In all these transformations the thioether used to form the sulfonium ylide is regenerated and so, catalytic amounts of thioether can be sufficient for complete conversion of a given carbene precursor into the 

Starting Material Reagents, Conditions Product Yield Ref. 

---

It is also possible to convert carbonyl groups into oxirane rings with cenain carbenoid synthons. The classical Darzens reaction, which involves addition of anions of a-chloroacetic esters, has been replaced by the addition of sulfonium ylides (R. Sowada, 1971 C.R. Johnson, 1979). 

Sulfonium ylides may be added to C N double bonds to yield aziridines in a formal [1 -t-2]-cycloaddition. Alkyl azides are decomposed upon heating or irradiating to yield ni-trenes, which may also undergo [ 1 + 2 -cycloaddition reactions to yield highly strained hetero-cycles (A.G. Hortmann, 1972). 

The dimethylsulfonium ylide (568) added readily to aroyl isocyanates to give the intermediate addition product (569). This on heating underwent ring closure with loss of dimethyl sulfide to form the 4-hydroxyoxazole (570) (73T1983). This normal C-acylation of the sulfonium ylide also leads to thiazoles with thiobenzoyl isocyanate in this case the initial acylation product was not isolated, the thiazole being obtained directly. 

The additional electronegative oxygen atom in the sulfoxonium salts stabilizes these ylides considerably, relative to the sulfonium ylides. ... 

Sulfonium ylides and suHoxonium ylides are useful reagents for converting ketones and aldehydes into epoxides. 

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. ... 

Since cbiral sulfur ylides racemize rapidly, they are generally prepared in situ from chiral sulfides and halides. The first example of asymmetric epoxidation was reported in 1989, using camphor-derived chiral sulfonium ylides with moderate yields and ee (< 41%) Since then, much effort has been made in tbe asymmetric epoxidation using sucb a strategy without a significant breakthrough. In one example, the reaction between benzaldehyde and benzyl bromide in the presence of one equivalent of camphor-derived sulfide 47 furnished epoxide 48 in high diastereoselectivity (trans cis = 96 4) with moderate enantioselectivity in the case of the trans isomer (56% ee). ... 

Due to the high reactivity of sulfonium ylide 2 for a,P-unsaturated ketone substrates, it normally undergoes methylene transfer to the carbonyl to give the corresponding epoxides. However, cyclopropanation did take place when 1,1-diphenylethylene and ethyl cinnamate were treated with 2 to furnish cyclopropanes 53 and 54, respectively. 

Upon addition of a base—triethylamine is often used—the sulfonium salt 7 is deprotonated to give a sulfonium ylide 8. The latter decomposes into the carbonyl compound 2 and dimethyl sulfide 9 through /3-elimination via a cyclic transition state. 

Both R and MMA radicals are found to be responsible for the photoinitiation process. Chaturvedi and coworkers [54,55] introduced phenyl dimethyl sulfonium-ylide cupric chloride and chromium thiophene carboxylate as the photoinitiator of styrene and MMA. No reaction mechanism was given for these systems. 

Pyridinium ylide is considered to be the adduct car-bene to the lone pair of nitrogen in pyridine. The validity of this assumption was confirmed by Tozume et al. [12J. They obtained pyridinium bis-(methoxycarbonyl) meth-ylide by the photolysis of dimethyl diazomalonate in pyridine. Matsuyama et al. [13] reported that the pyridinium ylide was produced quantitatively by the transylidalion of sulfonium ylide with pyridine in the presence of some sulfides. However, in their method it was not easy to separate the end products. Kondo and his coworkers [14] noticed that this disadvantage was overcome by the use of carbon disulfide as a catalyst. Therefore, they used this reaction to prepare poly[4-vinylpyridinium bis-(methoxycarbonyl) methylide (Scheme 12) by stirring a solution of poly(4-vinylpyridine), methylphenylsulfo-nium bis-(methoxycarbonyl)methylide, and carbon disulfide in chloroform for 2 days at room temperature. 

In an attempt to prepare sulfonium-ylide polymer, Tani-moto and coworkers [57,58] carried out the reaction of a sulfonium salt polymer with benzaldehyde in the presence of a base and obtained styrene oxide. The reaction was considered to process via a ylide polymer formation (Scheme 24), which may be unstable and has not been isolated. 

The structures of these ylide polymers were determined and confirmed by IR and NMR spectra. These were the first stable sulfonium ylide polymers reported in the literature. They are very important for such industrial uses as ion-exchange resins, polymer supports, peptide synthesis, polymeric reagent, and polyelectrolytes. Also in 1977, Hass and Moreau [60] found that when poly(4-vinylpyridine) was quaternized with bromomalonamide, two polymeric quaternary salts resulted. These polyelectrolyte products were subjected to thermal decyana-tion at 7200°C to give isocyanic acid or its isomer, cyanic acid. The addition of base to the solution of polyelectro-lyte in water gave a yellow polymeric ylide. 

Kondo maintained his interest in this area, and with his collaborators [62] he recently made detailed investigations on the polymerization and preparation of methyl-4-vinylphenyl-sulfonium bis-(methoxycarbonyl) meth-ylide (Scheme 27) as a new kind of stable vinyl monomer containing the sulfonium ylide structure. It was prepared by heating a solution of 4-methylthiostyrene, dimethyl-diazomalonate, and /-butyl catechol in chlorobenzene at 90°C for 10 h in the presence of anhydride cupric sulfate, and Scheme 27 was polymerized by using a, a -azobisi-sobutyronitrile (AIBN) as the initiator and dimethylsulf-oxide as the solvent at 60°C. The structure of the polymer was confirmed by IR and NMR spectra and elemental analysis. In addition, this monomeric ylide was copolymerized with vinyl monomers such as methyl methacrylate (MMA) and styrene. 

Until this work, the reactions between the benzyl sulfonium ylide and ketones to give trisubstituted epoxides had not previously been used in asymmetric sulfur ylide-mediated epoxidation. It was found that good selectivities were obtained with cyclic ketones (Entry 6), but lower diastereo- and enantioselectivities resulted with acyclic ketones (Entries 7 and 8), which still remain challenging substrates for sulfur ylide-mediated epoxidation. In addition they showed that aryl-vinyl epoxides could also be synthesized with the aid of a,P-unsaturated sulfonium salts lOa-b (Scheme 1.4). 

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]. 

The Stockman group has also studied reactions between the same imines and allyl sulfonium ylides (first reported by Hou and Dai [45]) [46], N-Sulfinyl vinylazir-... 

Arenediazonium salts also react with stabilized phosphonium, arsonium, pyridinium, and sulfonium ylides (12.111) in acetonitrile, yielding via the azo-onium salt (12.112) the azo-onium ylide (12.113, yellow to red), and in some cases the for-mazane (12.114) (Froyen and Juvvik, 1992). 

Thia-[2,3]-Wittig sigmatropic rearrangement of lithiated carbanions 47, obtained by deprotonation of the S-allylic sulfides 46, affords the thiols 48 or their alkylated derivatives 49. The corresponding sulfonium ylides 51, prepared by deprotonation of the sulfonium salts 50 also undergoes a [2,3]-sigmatropic shift leading to the same sulfides 49 [36,38] (Scheme 13). As far as stereochemistry is concerned, with crotyl (R R =H,R =Me) and cinnamyl (R, R =H,R =Ph) derivatives, it has been shown that the diastereoselectivity depends on the nature of the R substituent and on the use of a carbanion or an ylide as intermediate. 

A more direct access to the unstable and non isolated sulfonium ylides 58a- c is the reaction of diisopropyl diazomethylphosphonate 57 with allylic sulfides, catalyzed by Cu(II), Rh(II) [39], or ruthenium porphyrins.[40] For example, the a-phosphorylated y,d-unsaturated sulfides 59-61 are obtained through the [2,3] -sigmatropic rearrangement of 58a-c. This method allows the use of a greater variety of starting allylic sulfide substrates, such as 2-vinyl tetrahydrothiophene, or propargylic sulfides (Scheme 15). 

Another difference between dimethylsulfonium methylide and dimethylsulfoxonium methylide concerns the stereoselectivity in formation of epoxides from cyclohexanones. Dimethylsulfonium methylide usually adds from the axial direction whereas dimethylsulfoxonium methylide favors the equatorial direction. This result may also be due to reversibility of addition in the case of the sulfoxonium methylide.92 The product from the sulfonium ylide is the result the kinetic preference for axial addition by small nucleophiles (see Part A, Section 2.4.1.2). In the case of reversible addition of the sulfoxonium ylide, product structure is determined by the rate of displacement and this may be faster for the more stable epoxide. 

---