Ylides reactivity

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. ... 

Miscellaneous. Symmetrical olefins were obtained from reactive ylides and sulphur under fairly vigorous conditions. Yields were high when R = Ar, but the ethylidenephosphorane gave only 28% of hex-3-ene at 150 ""C in 1-methylnaphthalene. 

The reactive ylides give rise to cis-rich mixtures the moderately reactive ylides give rise to mixtures of cis and trans isomers. Using this approach, vitamin A acetate has been synthesized by the route shown in reaction 4. 

Deprotonation of t-amine oxides LDA (excess) converts trimethylamine oxide into a reactive ylide (a) that dimerizes to the dimethylpiperazine (2). If a is generated in the presence of an alkene, pyrrolidines (3) are formed via a 1,3-dipolar cycloaddition. The ylide reacts with cyclic alkenes to form bicyclic pyrrolidines in 40-90% yield.2... 

Reactive ylides give rapid reaction and subsequent rapid ring opening to give the (Z)-alkene ... 

The other examples useful for understanding of the problem are listed in the Brigas review <2004SOS(13)861> (Table 26). According to Butler <1996CHEC-II(4)621>, these reactions involve protonation at N-4 followed by deprotonation at C-5 giving a reactive ylide that is subjected to electrophilic attack (Equation 51). 

Carefully dried apparatus and solvent are a prerequisite of ozonation. A solution of the ylide (10 mmol) in dichloromethane (100-200 ml) was ozonized with an ozonizer (oxygen mixture) at - 40 to — 60°C, depending on the ylide. The most reactive ylides required only the equimolecular amount of ozone. When the peroxide test was negative the deep-coloured solution was concentrated and the residue purified by distillation, sublimation or recrystallization. More than 20 triketones were prepared in this way, in yields ranging between 65 and 92%. 

The addition of lithium salts during carbonyl olefination with reactive ylides causes a lowering of the (Z)-stereoselectivity. This effect is observed mainly in benzene or polar media such as ether (i.e. the more strongly the lithium cation is dissociated from its counterion u>) (Table 1). On the other hand, the presence of lithium salts seems to increase the amount of the (Z)-isomer in the reaction of moderate 28), a-fluorosubstituted 29) or resonance-stabilized ylides 30) (Table 1). 

The thermocatalytic Rh(ll) decomposition of diazo malonate in the presence of 3-phenyl-2/7-azirine 772d was proposed to give rise to an azirinium ylide 803 <2004TL6003>. This reactive ylide is preferentially transformed into 2-azabuta-l,3-diene derivative 804 or, with excess diazo compound, via reaction with the Rh-carbenoid, forms the 3,4-dihydro-2/7-pyrrole derivative 806 via intermediate 805 (Scheme 196). 

This ylide chemistry is treated in a number of monographs and reviews. The formation and properties of 77 and 78 were first dealt with by Corey et al. Reactive ylides are prepared from dialkyl sulfide and dialkyl sulfoxide in a non-aqueous medium. The solvent for the epoxidation reaction may be an aqueous basic solution. No side-reactions occur in a two-phase system or under the more recent phase-transfer conditions. ... 

Wittig reactions of diethyl oxalate with a variety of arylmethylene-triphenylphosphonium ylides under mild conditions provide a highly (Z)-stereoselective synthesis of ethyl 3-aryl-2-ethoxyacrylates (69). Wittig reactions of the a-keto amino acid derivative (70) with stabilized, semi-stabilized and reactive ylides have been used to prepare the synthetically... 

If there are electron-withdrawing substituents conjugated with the ylidic carbon atom, further dipolar structures such as 4 and 5 may make major contributions to the overall structure. Delocalization of the charge in this way frequently leads to the ylides being isolable. Such ylides are commonly described as stable ylides in this context stable is, in effect, a synonym for isolable. Many ylides are not, however, isolable, because of their high reactivity, in particular their very ready hydrolysis. In this article such ylides are called reactive ylides. Some other ylides, notably benzylylides, have reactivity intermediate between those ylides which are obviously stable or obviously reactive. They are described as semi-stabilized ylides. 

Many arsonium ylides dissolve in acids to form salts, from which they can be re-obtained by treatment with a base, as in the salt method for their preparation. The basicity of the ylides indicates the relative stabilities of the ylides and their salts and in so doing gives some guide to the stability of the ylides. Thus stable ylides are less readily protonated than are reactive ylides and require weaker bases for their generation from salts. 

Semi-stabilized arsonium ylides are intermediate in behaviour between stable and reactive ylides, and may provide alkenes and/or epoxides " °. In these cases factors such as the substituent groups on arsenic, and the nature of the solvent and of the base, may become important in determining the nature of the product this will be considered in more detail later (Section V.A.4). Small changes in the structure of the ylidic moiety may also have a marked effect for example, whereas triphenylarsonium jS-napththylmethylide reacts to give epoxide, the presence of a bromine atom at the adjacent a-position of the naphthalene ring results instead in the formation of alkenes . ... 

The first account of the preparation of an arsonium ylide (1) (see Section I) involved what is known as the salt method , namely the reaction of a halogeno compound with triphenylarsine to form an arsonium salt, which is then treated with a suitable base to provide the ylide (see Scheme 1). Stable ylides are frequently made and isolated by using aqueous alkali. Reactive ylides need anhydrous conditions and the use of a suitable strong base, and are used in situ. Thus triphenylarsonium methylide (25) has been prepared in solution " " it was isolated by using as base sodium amide in tetrahydrofuran under an atmosphere of nitrogenTrimethylarsonium methylide (26) has been made indirectly, by desilylation of the trimethylsilyl methylide (27) with trimethylsilanoP. Ylide... 

In 1960 triphenylstibonium methylide, Ph3Sb=CH2, was obtained in solution by treating methyltriphenylstibonium tetrafluoroborate with phenyllithium in ether When the resultant solution was treated with benzophenone, acid work-up provided high yields of triphenylstibine and diphenylacetaldehyde ", and it has been suggested that the latter product arose by acid-induced rearrangement of initially formed 1,1-diphenylethy-lene oxide, the most likely product from reaction of this reactive ylide with a carbonyl compound. 

The anions resulting from dissolving potassium in HMPT are also suitable for generating reactive ylides from their corresponding salts, H OT also turning out to be a favorable solvent for many ylide reactions (equation 12). ... 

Stabilized ylides react with mercury(Il) chloride giving salts, which can be deprotonated to the cone-sponding mercury substituted ylides (equation 48). Among reactive ylides only the trimethylsilylme-thylenetrimethylphosphorane can be transformed into its mercurated derivative (equation 49). 

Reactive ylides absorb carbon dioxide to give betaines (25), which on... 

Quaternized pyridines which have an R R CH group on the nitrogen are useful compounds because of the ease with which they react with bases to give reactive ylides the latter add on to some alkynes such as DMAD under mild conditions. The quaternized pyridines form ylides more readily when R is an electron-attracting group such as acyl, 4-nitrophenyl, tosyl, nitrile or carboxylic ester. When both R and R are electrophilic, as in (NQ2CH, ylide formation is very facile [2280, 2284, 2419, 2422, 2970]. The chemistry of iV-substituted pyridines [1870] and the use of azomethine ylides [2509] have been reviewed. 

A study comparing, under a range of conditions, diene synthesis by the two alternative Wittig routes, allylic ylide-saturated aldehyde (route 1) and reactive ylide-a,P-unsaturated aldehyde (route 2), has been reported. 9 por the system chosen (Scheme 2) the reactive ylide-a,P-unsaturated aldehyde route is clearly preferred in that the stereochemistry of the new double bond can be controlled more easily and there is little or no isomerisation of the double bond already present in the aldehyde. A route to symmetrically substituted polyenes containing an odd or even number of double bonds has been reported (Scheme 3).20 The Wittig reactions of ylides derived from... 

Telluroaldehydes have been generated and trapped for the first time by the reaction of benzylidenetriphenylphosphorane with "activated" tellurium (a method analogous to that previously used to prepare selenoaldehydes) (Scheme 22).71 A wide range of reactive ylides have been converted into the adducts (118) by reaction with borane.72 On heating, (118) rearrange to triphenylphosphine-monoalkylborane adducts (119) which undergo the expected hydroboration reactions with alkenes. A new route to phosphaalkenes (121) is available from the reaction of phosphinomethylenetriphenylphosphoranes (120) with Lewis acids.73 In the case of (120, R2=NPr 2) the compounds (121) can be isolated and in one case an X-ray structure was obtained. However, similar reactions of (120, r2=Bu ) lead to the dimers (122). 

The more reactive ylides discriminate less well among the aldehydes in competition experiments (p, KIE), in accordance with the reactivity-selectivity principle (RSP) (15b, 233). Thus, both the KIE and p values could be small. However, Yamataka et al. (223c) question the validity of the RSP in an ET sequence. Their arguments depend on the interpretation of KIE and model reactions for comparison, but it is not clear what experiment would be decisive. Objections to ET mechanisms based on the radical anion clock experiments discussed earlier may also not be decisive because of differences in the counterions. Futhermore, radical clock evidence against ET is available for aliphatic (not aromatic) aldehydes. 

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