Carbenes ylide formation

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... 

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... 

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). 

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). 

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... 

The intramolecular addition of acylcarbene complexes to alkynes is a general method for the generation of electrophilic vinylcarbene complexes. These reactive intermediates can undergo inter- or intramolecular cyclopropanation reactions [1066 -1068], C-H bond insertions [1061,1068-1070], sulfonium and oxonium ylide formation [1071], carbonyl ylide formation [1067,1069,1071], carbene dimerization [1066], and other reactions characteristic of electrophilic carbene complexes. 

Acceptor-substituted carbene complexes are highly reactive intermediates, capable of transforming organic compounds in many different ways. Typical reactions include insertion into o-bonds, cyclopropanation, and ylide formation. Generally, acceptor-substituted carbene complexes are not isolated and used in stoichiometric amounts, but generated in situ from a carbene precursor and transition metal derivative. Usually only catalytic quantities of a transition metal complex are required for complete conversion of a carbene precursor via an intermediate carbene complex into the final product. 

Several examples have been reported for furanone formation by intramolecular C-H insertion of electrophilic carbene complexes [1006,1148] (Table 4.7). Yields can, however, be low with some substrates, possibly as a result of several potential side-reactions. Oxonium ylide formation and hydride abstraction, in particular, [1090,1149-1152] (see Section 4.2.9) seem to compete efficiently with the formation of some types of furanones. 

Ylide formation, and hence X-H bond insertion, generally proceeds faster than C-H bond insertion or cyclopropanation [1176], 1,2-C-H insertion can, however, compete efficiently with X-H bond insertion [1177]. One problem occasionally encountered in transition metal-catalyzed X-H bond insertion is the deactivation of the (electrophilic) catalyst L M by the substrate RXH. The formation of the intermediate carbene complex requires nucleophilic addition of a carbene precursor (e.g. a diazocarbonyl compound) to the complex Lj,M. Other nucleophiles present in the reaction mixture can compete efficiently with the carbene precursor, or even lead to stable, catalytically inactive adducts L M-XR. For this reason carbene X-H bond insertion with substrates which might form a stable complex with the catalyst (e.g. amines, imidazole derivatives, thiols) often require larger amounts of catalyst and high reaction temperatures. 

If chiral catalysts are used to generate the intermediate oxonium ylides, non-racemic C-O bond insertion products can be obtained [1265,1266]. Reactions of electrophilic carbene complexes with ethers can also lead to the formation of radical-derived products [1135,1259], an observation consistent with a homolysis-recombination mechanism for 1,2-alkyl shifts. Carbene C-H insertion and hydride abstraction can efficiently compete with oxonium ylide formation. Unlike free car-benes [1267,1268] acceptor-substituted carbene complexes react intermolecularly with aliphatic ethers, mainly yielding products resulting from C-H insertion into the oxygen-bound methylene groups [1071,1093]. 

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... 

Intramolecular C-H bond insertion and ylide formation can compete with cyclopropanation. As shown in Figure 4.21, however, the chemoselectivity of the intermediate carbene complex can sometimes be controlled by the remaining metal-bound ligands [21,990,1075,1081,1223]. 

Ab initio and RRKM calculations indicate that the reactions of C, CH, and (H2C ) with acetylene occur with no barrier." Laser flash photolysis of the cyclopropanes (69) and (70) was used to generate the corresponding dihalocarbenes. The absolute rate constant for the formation of a pyridine ylide from Br2C was (4-11) x 10 lmoP s. The rates of additions of these carbenes to alkenes were measured by competition with pyridine ylide formation and the reactivity of BrClC was found to resemble that of Br2C rather than CI2C . 

Previous studies of the photochemistry of alkylchlorodiazirines have shown that the yield of trappable carbene is sensitive to the alkylcarbene structure. A laser flash photolysis study of phenanthridenes (91), precursors of alkylchlorocarbenes, in the presence of pyridine, has ruled out the intermediacy of a carbene-pyridine complex which partitions between pyridine-ylide formation and [1,2]-H shift. ... 

The absolute rate constants for oxygen and sulfur transfer to a range of carbenes (dialkyl, cycloalkylidene, alkylchloro, diaryl, arylchloro, arylalkoxy, and dialkoxy), generated by laser flash photolysis of diazirine or oxadiazoline precursors, were determined. No evidence was seen for ylide formation and a concerted mechanism via an ylide-like transition state was proposed. 

Wenkert and Khatuya (51) examined the competition between direct insertion of a carbene into furan (via cyclopropanation) and ylide formation with reactive side-chain functionality such as esters, aldehydes, and acetals. They demonstrated the ease of formation of aldehyde derived carbonyl ylides (Scheme 4.30) as opposed to reaction with the electron-rich olefin of the furan. Treatment of 3-furfural (136) with ethyl diazoacetate (EDA) and rhodium acetate led to formation of ylide 137, followed by trapping with a second molecule of furfural to give the acetal 138 as an equal mixture of isomers at the acetal hydrogen position. 

Reaction with pyridine leads to the formation of a UV-active pyridinium ylide. Rate constants for the alkylcarbene reaction(s) can be extracted from the intercept of the linear correlation of feobs for ylide formation versus the pyridine concentration. Consider first the 1,2-H shift that converts chloromethylcarbene (48) into vinyl chloride (Scheme 7.17). The LFP experiments show that the H shift occurs with k= 1.2 — 3.0 X 10 s in isooctane, cyclohexane, or dichloroethane at 21-25 The rearrangement is fast, but not ultrafast carbene (48) has a lifetime... 

Ethers, sulfides, amines, carbonyl compounds, and imines are among the frequently encountered Lewis bases in the ylide formation from such metal carbene complex. The metal carbene in the ylide formation can be divided into stable Fisher carbene complex and unstable reactive metal carbene intermediates. The reaction of the former is thus stoichiometric and the latter is usually a transition metal complex-catalyzed reaction of a-diazocarbonyl compounds. The decomposition of a-diazocarbonyl compounds with catalytic transition metal complex has been the most widely used approach to generate reactive metal carbenes. For compressive reviews, see Refs 1,1a. 

Stereoselective oxonium ylide reaction, in particular the asymmetric catalysis, has been a problem of considerable challenge in this field. Since the first report by McKervey and co-workers in the asymmetric induction in metal carbene-mediated ylide formation/[2,3]-sigmatropic rearrangement in 1992, there have been efforts being directed... 

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