Sulfoxonium ylide

Similaf considerations apply to the sulfonium and sulfoxonium ylides. These ylides are formed by deprotonation of the corresponding positively charged sulfur-containing cations. 

In addition, NaOMe, and NaNH2, have also been employed. Applieation of phase-transfer conditions with tetra-n-butylammonium iodide showed marked improvement for the epoxide formation. Furthermore, many complex substituted sulfur ylides have been synthesized and utilized. For instance, stabilized ylide 20 was prepared and treated with a-D-a/lo-pyranoside 19 to furnish a-D-cyclopropanyl-pyranoside 21. Other examples of substituted sulfur ylides include 22-25, among which aminosulfoxonium ylide 25, sometimes known as Johnson s ylide, belongs to another category. The aminosulfoxonium ylides possess the configurational stability and thermal stability not enjoyed by the sulfonium and sulfoxonium ylides, thereby are more suitable for asymmetric synthesis. 

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 anion from 1,3,5-trithiane hexaoxide has been silylated and thence converted into a sulfoxonium ylide <96CB161>. 

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. 

Aldol addition and related reactions of enolates and enolate equivalents are the subject of the first part of Chapter 2. These reactions provide powerful methods for controlling the stereochemistry in reactions that form hydroxyl- and methyl-substituted structures, such as those found in many antibiotics. We will see how the choice of the nucleophile, the other reagents (such as Lewis acids), and adjustment of reaction conditions can be used to control stereochemistry. We discuss the role of open, cyclic, and chelated transition structures in determining stereochemistry, and will also see how chiral auxiliaries and chiral catalysts can control the enantiose-lectivity of these reactions. Intramolecular aldol reactions, including the Robinson annulation are discussed. Other reactions included in Chapter 2 include Mannich, carbon acylation, and olefination reactions. The reactivity of other carbon nucleophiles including phosphonium ylides, phosphonate carbanions, sulfone anions, sulfonium ylides, and sulfoxonium ylides are also considered. 

Ylides other than acceptor-substituted diazomethanes have only occasionally been used as carbene-complex precursors. lodonium ylides (PhI=CZ Z ) [1017,1050-1056], sulfonium ylides [673], sulfoxonium ylides [1057] and thiophenium ylides [1058,1059] react with electrophilic transition metal complexes to yield intermediates capable of undergoing C-H or N-H insertions and olefin cyclopropanations. 

Other synthetic routes to benzazepines involving ring expansion of six-membered heterocycles include the action of diazomethane (77CPB321), sulfonium ylides (77H(7)37> or acyl halides (75T1991) on quaternary 3,4-dihydroisoquinolines that of sulfoxonium ylides on quaternary quinolines (74IJC(B)1238) and the zinc-acetic acid reduction of quaternary 1-acyltetrahydroisoquinolines (77BSF893). Photoaddition of acyl- or aryl-nitrenes to the exocyclic alkene bond of 2-methylene-1,2-dihydroquinolines results in ring expansion to... 

Stability of both the parent system and the S- oxide is conferred by the presence of electron-withdrawing substituents on the carbon framework, especially at positions 2, 4 and 6, while electron-donating substituents on sulfur also help. Compounds (48), (49) and (50) illustrate these conclusions, as they are air-stable, isolable species (74CL1101). Exactly analogous factors acting on stability are seen with acyclic sulfonium and sulfoxonium ylide compounds. 

The configuration of these complexes were established on the basis of IR and H-NMR spectra (62). When triphenylarsine was reacted with sulfoxonium ylide complex, pentacarbonyl triphenylarsonium ylide-chromium complex was obtained (95). 

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

Treatment of wortmannin with trimethylsulfoxonium ylide gave the ring expanded product 2 (R = H). The Lilly chemists considered two possible mechanisms for the formation of 2 and preferred one of them on the basis that use of the perdeuterated sulfoxonium ylide gave exclusively the deuterated product 2 (R = D). 

A series of tetrasubstituted sulfoxonium ylides 89a-h were synthesized from 83 in a two-step reaction via 2,4-disubstituted disulfones 88a-h, which were converted into the final ylides upon reactions with very strongly silylating agents, such as C4F9-SO2-OR, where R = Si(Alkyl)3 (Scheme 10) <1996CB161>. 

Dianions of alkyl-substituted sulfoxonium ylides 91a,b,e,f were prepared from 83 also by a two-step procedure via 2,4-dialkylated disulfones 90a-g. Deprotonation of 83 and alkylation yielded a family of bis-sulfones 90a-g, which upon a second deprotonation by treatment with an appropriate base were converted into the corresponding salts 91a,b,e,f (Scheme 11) <1996CB161>. 

Fig. 9.1. Representative phosphonium, sulfonium, and sulfoxonium ylides— formation reactions and valence bond formulas.

In analogy with the nomenclature introduced previously, they are referred to as phos-phonium, sulfonium, and sulfoxonium ylides, respectively, or as P or S ylides. 

The ionic representation of the ylides in Figure 9.1 shows only one of two conceivable resonance forms of such species. In contrast to the N atom in the center of the N ylides, the P or S atoms in the centers of the P and S ylides (Figure 9.1) may exceed their valence electron octets and share a fifth electron pair. For P and S ylides one can therefore also write a resonance form with a C=P or C=S double bond, respectively these are resonance forms free of formal charges (Figure 9.1). For the sulfoxonium ylide there is a second resonance form in which the S atom exceeds its valence electron octet however, this does contain formal charges. Resonance forms of ylides in which the heteroatom exceeds its valence electron octet are called ylene resonance forms. The ene part of the designation ylene refers to the double bond between the heteroatom and the deprotonated alkyl group. 

Both S ylides from Figure 9.1 react with a,/3-unsaturated esters to give cyclopropanes (Section 9.2). Sulfoxonium ylides also react with a,j8-unsaturated carbonyl compounds to give cyclopropanes (Section 9.2). Sulfonium ylides cannot do this because they react to form epoxides. 

The reason for this complementarity is that the CH2 group of the sulfoxonium ylide is less nucleophilic than that of the sulfonium ylide. In the first case the CH2 group is adjacent to the substituent Me2S+=0 and in the second case it is adjacent to the substituent Me2S+. The extra oxygen in the first substituent reduces the nucleophilicity of the sulfoxonium ylide because it stabilizes the negative charge of its carbanionic moiety especially well. 

Fig. 9.4. Comparison of sulfonium and sulfoxonium ylides I— diastereoselectivity in the formation of epoxides. The sulfoxonium ylide attacks the carbonyl group equatorially and the sulfonium ylide attacks axially.

Fig. 9.5. Comparison of sulfonium and sulfoxonium ylides II—chemoselectivity in the reaction with an a,/3-unsaturated carbonyl compound. The sulfoxonium ylide reacts through the enolate intermediate A, whereas the sulfonium ylide reacts through the alkoxide intermediate B.

Ylide can be viewed as a special carbanion in which the negative charge on carbon is stabilized by an adjacent positively charged heteroatom. The most common ylides are phospho-nium ylides, sulfur ylides (sulfonium and sulfoxonium ylides) and certain nitrogen-based ylides (ammonium, azomethine, pyridinium and nitrile ylides). In addition to synthetically important phosphorus, sulfur and nitrogen, ylides of tin (Sn) and iodine (I) have been developed in recent years. 

Unstabilized sulfonium ylides such as dimethylsulfonium methylide (3.45) and stabilized sulfoxonium ylides such as dimethylsulfoxonium methylide (3.46) are the most widely used sulfur ylides. 

Unstabilized sulfonium ylides and stabilized sulfoxonium ylides show different reactions with a,P-unsaturated carbonyl compounds the former give epoxides and the latter give cyclopropanes. The epoxide formation (i.e. 1,2-addition) is kinetically favourable while cyclopropane formation (i.e. 1,4-addition, Michael addition) is energetically favourable. 

From carbodiphosphoranes R3P=C=PR3 and dialkyl-gold(III) halides, cyclic ylide complexes containing four Au-C <7-bonds are obtained in a multiple transylidation reaction (equation 24). Related thiophosphorus ylides and sulfonium and sulfoxonium ylides are equally effective in the formation of Au-C <7-bonds, and a series of analogous gold thiophosphonium and sulfoxonium-methyhde complexes is available (equations 25-27). ... 

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