Ylides formation

Sulfur ylides contain a carbanion, which is stabilizea oy an adjacent positively-charged sulfur. Ylides derived from alkylsulfonium salts are usually generated and utilized at low temperatures. Oxosulfonium ylides are, however, stable near room temperature. The most common method of ylide formation is deprotonation of a sulfonium salt. What has been said... 

Thiiranium salts, l-methyI-2-methylene-1-oxide, 7, 134 Thiiranium salts, I-phenyl-collisional activation spectra, 7, 135 Thiiranium tetrafluoroborate, 2,3-di-t-butyl-l-methyl-inversion barriers, 7, 134 Thiiranium ylides formation, 7, 174, 175 Thiiran-2-ones... 

Halofluoroalkenes may be prepared by using fluorodihalomethanes or fluoro-halomethanes in olefination procedures similar to those descnbed above. Ruoro-trichloromethane treated with tris(dimethylamino)phosphine forms the corresponding phosphomum salt, which can then be used in the Wirtig procedure. The reaction depends on the nature of the solvent in tetrahydrofuran, little olefination if any occurs however, when benzomtrile is added to the mixture, ylide formation is promoted [50] (equation 48) (Table 19). 

The rhodium-catalyzed tandem carbonyl ylide formation/l,3-dipolar cycloaddition is an exciting new area that has evolved during the past 3 years and high se-lectivities of >90% ee was obtained for both intra- and intermolecular reactions with low loadings of the chiral catalyst. 

These carbene (or alkylidene) complexes are used for various transformations. Known reactions of these complexes are (a) alkene metathesis, (b) alkene cyclopropanation, (c) carbonyl alkenation, (d) insertion into C-H, N-H and O-H bonds, (e) ylide formation and (f) dimerization. The reactivity of these complexes can be tuned by varying the metal, oxidation state or ligands. Nowadays carbene complexes with cumulated double bonds have also been synthesized and investigated [45-49] as well as carbene cluster compounds, which will not be discussed here [50]. 

Transition metal-catalyzed carbenoid transfer reactions, such as alkene cyclopro-panation, C-H insertion, X-H insertion (X = heteroatom), ylide formation, and cycloaddition, are powerful methods for the construction of C-C and C-heteroatom bonds [1-6]. In contrast to a free carbene, metallocarbene-mediated reactions often proceed stereo- and regioselectively under mild conditions with tolerance to a wide range of functionalities. The reactivity and selectivity of metallocarbenes can be... 

Based on this work, it has been proposed that a specifically solvated carbene (Scheme 4.6, Reaction 2) nndergoes bimolecular reactions at slower rates than a free carbene (Scheme 4.6, Reaction 1). Other alternatives that mnst be considered are participation of rapid and reversible ylide formation with the ylide acting as a... 

Alkyltriphenylphosphonium halides are only weakly acidic, and a strong base must be used for deprotonation. Possibilities include organolithium reagents, the anion of dimethyl sulfoxide, and amide ion or substituted amide anions, such as LDA or NaHMDS. The ylides are not normally isolated, so the reaction is carried out either with the carbonyl compound present or with it added immediately after ylide formation. Ylides with nonpolar substituents, e.g., R = H, alkyl, aryl, are quite reactive toward both ketones and aldehydes. Ylides having an a-EWG substituent, such as alkoxycarbonyl or acyl, are less reactive and are called stabilized ylides. 

The stereoselectivity of the Wittig reaction is believed to be the result of steric effects that develop as the ylide and carbonyl compound approach one another. The three phenyl substituents on phosphorus impose large steric demands that govern the formation of the diastereomeric adducts.240 Reactions of unstabilized phosphoranes are believed to proceed through an early TS, and steric factors usually make these reactions selective for the d.v-alkcnc.241 Ultimately, however, the precise stereoselectivity is dependent on a number of variables, including reactant structure, the base used for ylide formation, the presence of other ions, solvent, and temperature.242... 

In several cases of syntheses of highly functionalized molecules, use of CH3Li-LiBr for ylide formation has been found to be advantageous. For example, in the synthesis of milbemycin D, Crimmins and co-workers obtained an 84% yield with 10 1 Z E selectivity.251 In this case, the more stable E-isomer was required and it was obtained by I2-catalyzed isomerization. 

Dehydrogenation has been used as a method for azomethine ylide formation. Treatment of compound 206 with iV-methylmaleimide in the presence of palladium black gives a 1 1 mixture of the endo- and f .tf-diastereomcrs 207 and 208, in 65% combined yield <1989J(P1)198> (Equation 24). 

As has been described for allyl bromide (see preceding paragraph), allyl sulfides and allyl phenyl selenide react with 6-diazopenicillanates 134 under Cu(acac)2 catalysis to give the products of ylide formation and subsequent [2,3] rearrangement 155-159). Both C-6 epimers are formed. The yields are better than with BF3 Et20 catalysis, and, in contrast to the Lewis acid case, no 6[Pg.139]

The choice of the catalyst is crucial when it comes to competition between intramolecular cyclopropanation and intramolecular carbonyl ylide formation by a... 

The distinction between Pd and Rh catalysts was also verified for diazoketone 190. In this case, the carbonyl ylide was trapped by intramolecular [3+2] cycloaddition to the C=C bond195. Decomposition of bis-diazoketone 191 in the presence of CuCl P(OEt)3 or Rh2(OAc)4 led to the pentacyclic ketone 192 most remarkably, one diazoketone unit reacted by cyclopropanation, the second one by carbonyl ylide formation 194). With [(r 3-C3H5)PdCl]2, a non-separable mixture containing mostly polymers was obtained, although bis-diazoketones with one or two allyl side chains instead of the butenyl groups underwent successful twofold cyclopropanation 196). 

Rhodium(II) acetate was found to be much more superior to copper catalysts in catalyzing reactions between thiophenes and diazoesters or diazoketones 246 K The outcome of the reaction depends on the particular diazo compound 246> With /-butyl diazoacetate, high-yield cydopropanation takes place, yielding 6-eco-substituted thiabicyclohexene 262. Dimethyl or diethyl diazomalonate, upon Rh2(OAc)4-catalysis at room temperature, furnish stable thiophenium bis(alkoxycarbonyl)methanides 263, but exclusively the corresponding carbene dimer upon heating. In contrast, only 2-thienylmalonate (36 %) and carbene dimer were obtained upon heating the reactants for 8 days in the presence of Cul P(OEt)3. The Rh(II)-promoted ylide formation... 

Some functionalized thiophenes have been investigated in order to assess the scope of ylide-derived chemistry. As already mentioned, 2-(hydroxymethyl)thiophene still gives the S-ylide upon Rh2(OAe)4-catalyzed reaction with dimethyl diazomalonate 146 but O/H insertion instead of ylide formation seems to have been observed by other workers (Footnote 4 in Ref. 2S4)). From the room temperature reaction of 2-(aminomethyl)thiophene and dimethyl diazomalonate, however, salt 271 was isolated quite unexpectedly 254). Rh2(OAc)4, perhaps deactivated by the substrate, is useless in terms of the anticipated earbenoid reactions. Formation of a diazo-malonic ester amide and amine-catalyzed cyclization to a 5-hydroxytriazole seem to take place instead. 

Intramolecular carbonyl ylide formation was also invoked to explain the formation of the AH-1,3-oxazin-5(6//)-ones 291a, b upon copper-catalyzed decomposition of diazoketones 290a, b 270 >. Oxapenam 292, obtained from 290b as a minor product, originates from an intermediary attack of the carbenic carbon at the sulfur atom. In fact, this pathway is followed exclusively if the C(Me, COOMe) group in 290b is replaced by a CH2 function (see Sect. 7.2). 

Intramolecular oxonium ylide formation is assumed to initialize the copper-catalyzed transformation of a, (3-epoxy diazomethyl ketones 341 to olefins 342 in the presence of an alcohol 333 . The reaction may be described as an intramolecular oxygen transfer from the epoxide ring to the carbenoid carbon atom, yielding a p,y-unsaturated a-ketoaldehyde which is then acetalized. A detailed reaction mechanism has been proposed. In some cases, the oxonium-ylide pathway gives rise to additional products when the reaction is catalyzed by copper powder. If, on the other hand, diazoketones of type 341 are heated in the presence of olefins (e.g. styrene, cyclohexene, cyclopen-tene, but not isopropenyl acetate or 2,3-dimethyl-2-butene) and palladium(II) acetate, intermolecular cyclopropanation rather than oxonium ylide derived chemistry takes place 334 ). 

The reaction of carbenes or carbenoids with compounds containing S—S bonds is likely to begin with sulfonium ylide formation subsequent [1,2] rearrangement then produces a formal insertion product of the carbene moiety into the S—S bond152 b). 

The q1-coordinated carbene complexes 421 (R = Ph)411 and 422412) are rather stable thermally. As metal-free product of thermal decomposition [421 (R = Ph) 110 °C, 422 PPh3, 105 °C], one finds the formal carbene dimer, tetraphenylethylene, in both cases. Carbene transfer from 422 onto 1,1-diphenylethylene does not occur, however. Among all isolated carbene complexes, 422 may be considered the only connecting link between stoichiometric diazoalkane reactions and catalytic decomposition [except for the somewhat different results with rhodium(III) porphyrins, see above] 422 is obtained from diazodiphenylmethane and [Rh(CO)2Cl]2, which is also known to be an efficient catalyst for cyclopropanation and S-ylide formation with diazoesters 66). 

The Ge(TMTAA) complex and the well known Sn(TMTAA) complex undergo facile oxidative addition reactions and reverse ylide formation with Mel and C6F5I because of the reactive M(II) (M = Sn, Ge) lone pair of electrons. In case of the oxidation with Mel it was assumed that, in solution, an ionic-covalent equilibrium exists (equation 48)95. 

Spectroscopically invisible carbenes can be monitored by the ylide method .92 Here, the carbene reacts with a nucleophile Y to form a strongly absorbing and long-lived ylide, competitively with all other routes of decay. Although pyridine (Py) stands out as the most popular probe, nitriles and thiones have also been used. In the presence of an additional quencher, the observed pseudo-first-order rate constant for ylide formation is given by Eq. 2.92,93 A plot of obs vs. [Q] at constant [Y ] will provide kq. With Q = HX, complications can arise from protonation of Y and/or the derived ylides. The available data indicate that alcohols are compatible with the pyridine-ylide probe technique. 

Relative rates of some prototypical carbenes, obtained by Stem-Volmer methods, are listed in Table 2. Although many of these carbenes have triplet ground states, reaction with nucleophiles Y occurs prior to spin equilibration. Most often, ylide formation with solvent molecules was analysed in terms of Eq. 3. The pyridine-ylide served as the probe for 154. 

Ifcobs is directly proportional to pyridine concentration. Therefore a plot of kobs vs. [pyridine] is linear, with a slope (k ) equal to the second order rate constant for ylide formation, and an intercept (k0) equal to the sum of all processes that destroy the carbene in the absence of pyridine (e.g.) intramolecular reactions, carbene dimerization, reactions with solvent, and, in the case of diazirine or diazo carbene precursors, azine formation. 

Although we are not specifically concerned here with kpp and the kinedcs of carbene-pyridine ylide formation, we note that the magnitude of is directly related to the structure and reactivity of the carbene. fcpyr ranges from 105 M s-1 for ambiphilic alkoxycarbenes to 109-10I° M-1 s 1 for electrophilic halocarbenes or alkylcarbenes. Very nucleophilic carbenes (MeOCOMe) do not react with pyridine.13... 

Here the alkene and pyridine will compete for the carbene at a constant concentration of pyridine the observed pseudo first order rate constant for ylide formation will increase with increasing alkene concentration. A plot of kobs vs. [alkene] will be linear with a slope of kad, which is the rate constant for the carbene/alkene addition reaction affording cyclopropane 5 (Scheme 1). 

Equation 1 cannot be used to extract k0 for carbenic rearrangements in the region of A. There, however, a Stem-Volmer analysis can be applied wherein the optical yield of ylide as a function of pyridine concentration is used to obtain ko.4 The optical yield of ylide formation, Ay, is defined in Eq. 3,... 

Substitution of a measured or estimated value of ifcpyr (e.g., 109 for alkylcar-benes), affords the value of k0 for those processes that destroy the carbene other than ylide formation. The inverse of <, can be taken as r0, the lifetime of the... 

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