Carbenes dimerization reactions

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. 

Transition metal—bonded carbene dimerization reactions are well-known for example, the methylene complex(57)decomposes in to give a coordinated ethylene complex [11]. 

Interestingly, cobalt porphyrin catalysts tend to prevent carbene dimerization reactions, and allow cyclopropanation reactions with electron-deficient alkenes. This feature illustrates the more nucleophilic behavior of the carbenoid species formed as compared to typical electrophilic Fischer carbenes. The enhanced nucleophilic character of the carbene reduces its tendency to dimerize and allows reactions with more electron-deficient olefins. 

Thorough investigations with dimethyl diazomalonate and catalysts of the type (RO)3P CuX have revealed that the efficiency of competing reaction paths, the synjanti or EjZ selectivity in cyclopropane formation as well as the cis/trans ratio of carbene dimers depend not only on catalyst concentration and temperature but also on the nature of R58) and of the halide anion X 57 6". Furthermore, the cyclopropane yield can be augmented in many cases at the expense of carbene dimer... 

The common by-products obtained in the transition-metal catalyzed reactions are the formal carbene dimers, diethyl maleate and diethyl fumarate. In accordance with the assumption that they owe their formation to the competition of olefin and excess diazo ester for an intermediate metal carbene, they can be widely suppressed by keeping the actual concentration of diazo compound as low as possible. Usually, one attempts to verify this condition by slow addition of the diazo compound to an excess (usually five- to tenfold) of olefin. This means that the addition rate will be crucial for the yields of cyclopropanes and carbene dimers. For example, Rh6(CO)16-catalyzed cyclopropanation of -butyl vinyl ether with ethyl diazoacetate proceeds in 69% yield when EDA is added during 30 minutes, but it increases to 87 % for a 6 h period. For styrene, the same differences were observed 65). 

Palladium(II) acetate was found to be a good catalyst for such cyclopropanations with ethyl diazoacetate (Scheme 19) by analogy with the same transformation using diazomethane (see Sect. 2.1). The best yields were obtained with monosubstituted alkenes such as acrylic esters and methyl vinyl ketone (64-85 %), whereas they dropped to 10-30% for a,p-unsaturated carbonyl compounds bearing alkyl groups in a- or p-position such as ethyl crotonate, isophorone and methyl methacrylate 141). In none of these reactions was formation of carbene dimers observed. 7>ms-benzalaceto-phenone was cyclopropanated stereospecifically in about 50% yield PdCl2 and palladium(II) acetylacetonate were less efficient catalysts 34 >. Diazoketones may be used instead of diazoesters, as the cyclopropanation of acrylonitrile by diazoacenaph-thenone/Pd(OAc)2 (75 % yield) shows142). 

As has already been mentioned for cyclopropanation of olefins, the diazoester should be added slowly to the mixture of alkyne and Rh2(OAc)4, in order to minimize formation of carbene dimers. The reaction works well with mono- and... 

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... 

Reaction of the imine moiety of 278 with excess ethyl diazoacetate in the presence of Cu(acac)2 led to the cyclopentane-annulated product 279 the structure of which was confirmed by an X-ray analysis 262. It is assumed that 279 results from reaction between a carbene dimer (diethyl fumarate) and an intermediate N-ylide or the... 

Similar to the intramolecular insertion into an unactivated C—H bond, the intermolecular version of this reaction meets with greatly improved yields when rhodium carbenes are involved. For the insertion of an alkoxycarbonylcarbene fragment into C—H bonds of acyclic alkanes and cycloalkanes, rhodium(II) perfluorocarb-oxylates 286), rhodium(II) pivalate or some other carboxylates 287,288 and rhodium-(III) porphyrins 287 > proved to be well suited (Tables 19 and 20). In the era of copper catalysts, this reaction type ranked as a quite uncommon process 14), mainly because the yields were low, even in the absence of other functional groups in the substrate which would be more susceptible to carbenoid attack. For example, CuS04(CuCl)-catalyzed decomposition of ethyl diazoacetate in a large excess of cyclohexane was reported to give 24% (15%) of C/H insertion, but 40% (61 %) of the two carbene dimers 289). 

Insertion of a ketocarbene moiety into a C—O bond of orthoesters is normally performed with catalysis by BF3 Et20. Copper(II) trifiouromethanesulfonate was found to be a similarly efficient catalyst also, at least in some cases, whereas Rh2(OAc)4 was much less suited to promote this transformation l60). Besides the C/O insertion product 343, the alcohol insertion product 344 and, in reactions with ethyl diazoacetate, the formal carbene dimers were obtained. In agreement with BF3 EtzO, Cu(OTf)2 did not bring about insertion into a C—O bond of trimethyl... 

Occurence of olefins which are, formally speaking carbene dimers, as well as of similar products (R2C=N—N=CR2, R2CH—CHR2) represents an usually unwanted side-reaction which the chemist endeavors to suppress as far as possible. Nevertheless, conditions for high-yield synthesis of carbene dimers from several diazo compounds have been reported in the past13,141. Some novel examples, published since the last review14) was written, are listed in Table 22. 

A somewhat unusual copper catalyst, namely a zeolite in which at least 25% of its rhodium ions had been exchanged by Cu(II), was active in decomposition of ethyl diazoacetate at room temperature 372). In the absence of appropriate reaction partners, diethyl maleate and diethyl fumarate were the major products. The selectivity was a function of the zeolite activation temperature, but the maleate prevailed in all cases. Contrary to the copper salt-catalyzed carbene dimer formation 365), the maleate fumarate ratio was found to be relatively constant at various catalyst concentrations. When Cu(II) was reduced to Cu(I), an improved catalytic activity was observed. 

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 most common ligands are those derived from imidazole and benzimidazol (Scheme 54), followed by the (benz)thiazols. The free Wanzlick-Arduengo carbenes can be isolated and employed for the synthesis of the complexes, but often it is more convenient to prepare the carbenes in situ from the dimers or the corresponding onium salts, or to use carbene-transfer reactions.256-259... 

An alternative strategy for selective intermolecular G-H insertions has been the use of rhodium carbenoid systems that are more stable than the conventional carbenoids derived from ethyl diazoacetate. Garbenoids derived from aryldiazoacetates and vinyldiazoacetates, so-called donor/acceptor-substituted carbenoids, have been found to display a very different reactivity profile compared to the traditional carbenoids.44 A clear example of this effect is the rhodium pivalate-catalyzed G-H insertion into cyclohexane.77 The reaction with ethyl diazoacetate gave the product only in 10% yield, while the parallel reaction with ethyl phenyldiazoacetate gave the product in 94% yield (Equation (10)). In the first case, carbene dimerization was the dominant reaction, while this was not observed with the donor/acceptor-substituted carbenoids. 

The most common byproducts encountered in cyclopropanations with diazoalkanes as carbene precursors are azines and carbene dimers , i.e. symmetric olefins resulting from the reaction of the intermediate carbene complex with the diazoalkane. The formation of these byproducts can be supressed by keeping the concentration of diazoalkane in the reaction mixture as low as possible. For this purpose, the automated, slow addition of the diazoalkane to a mixture of catalyst and substrate (e.g. by means of a pump or a syringe motor) has proven to be a very valuable technique. 

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. 

The normal byproducts formed during the transition metal-catalyzed decomposition of diazoalkanes are carbene dimers and azines [496,1023,1329], These products result from the reaction of carbene complexes with the carbene precursor. Their formation can be suppressed by slow addition (e.g. with a syringe motor) of a dilute solution of the diazo compound to the mixture of substrate and catalyst. Carbene dimerization can, however, also be a synthetically useful process. If, e.g., diazoacetone is treated with 0.1% RuClCpIPPhjij at 65 °C in toluene, cw-3-hexene-2,5-dione is obtained in 81% yield with high stereoselectivity [1038]. 

Scheme 8.13 Dynamic covalent polymers based on carbine dimerization, (a) Preparation of difnnctional carbene 58 and polymerization of 58 via carbene dimerization (b) Chain transfer reaction of 59 by the agency of monofnnctional carbene 60, and (c) Formation of the organometallic copolymer 62 by the insertion of PdCl [45],...

The most spectacular application of the donor/acceptor-substituted carbenoids has been intermolecular C-H activation by means of carbenoid-induced C-H insertion [17]. Prior to the development of the donor/acceptor carbenoids, the intermolecular C-H insertion was not considered synthetically useful [5]. Since these carbenoid intermediates were not sufficiently selective and they were very prone to carbene dimerization, intramolecular reactions were required in order to control the chemistry effectively [17]. The enhanced chemoselectivity of the donor/acceptor-substituted carbenoids has enabled intermolecular C-H insertion to become a very practical enantioselective method for C-H activation. Since the initial report in 1997 [121], the field of intermolecular enantioselective C-H insertion has undergone explosive growth [14, 15]. Excellent levels of asymmetric induction are obtained when these carbenoids are derived... 

Thermolysis of 2-diazo-l,3-dithiane, prepared in situ from the reaction of 2-lithio-2-trimethylsilyl-l,3-dithiane and tosyl azide, occurs already below 0°C. The resulting carbene dimerizes efficiently even in the presence of alkenes and alkynes to give bis(l,3-dithianylidene) in 78% yield (Scheme 41) <1997T9269>. 

First, it should be repeated that despite early and recent claims, no examples of thermal dissociation of alkenes into carbenes (the reverse reaction of the carbene dimerization) are known.However, in their recent paper, Lemal and co-worker pointed out that electrophiles can catalyze the dissociation of tetraaminoalkenes. 

Substituted cyclopropylidenes have been shown to participate in both inter-and intramolecular addition reactions with olefins. The resulting products are spiropentane derivatives as well as carbene dimers which are formed as side-products [99, 100]. In the absence of olefinic reaction products the latter may even become the main products [99 b],... 

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