Ethyl diazoacetate, decomposition

The [Cu(Bp)] system has been employed to investigate kinetics of the ethyl diazoacetate decomposition reaction in the presence or absence of olefin. The available data have allowed the proposition for a copper-mediated olefin cyclopropanation reaction. It has been proposed that the real catalyst is a 14-electron species, independent of the nature of the ligand bonded to the copper center.50... 

Catalytic, enantioselective cyclopropanation enjoys the unique distinction of being the first example of asymmetric catalysis with a transition metal complex. The landmark 1966 report by Nozaki et al. [1] of decomposition of ethyl diazoacetate 3 with a chiral copper (II) salicylamine complex 1 (Scheme 3.1) in the presence of styrene gave birth to a field of endeavor which still today represents one of the major enterprises in chemistry. In view of the enormous growth in the field of asymmetric catalysis over the past four decades, it is somewhat ironic that significant advances in cyclopropanation have only emerged in the past ten years. 

Incorporation of the phenethyl moiety into a carbocyclic ring was at first sight compatible with amphetamine-like activity. Clinical experience with one of these agents, tranylcypromine (79), revealed the interesting fact that this drug in fact possessed considerable activity as a monamine oxidase inhibitor and as such was useful in the treatment of depression. Decomposition of ethyl diazoacetate in the presence of styrene affords a mixture of cyclopropanes in which the trans isomer predominates. Saponification gives acid 77. Conversion to the acid chloride followed by treatment with sodium azide leads to the isocyanate, 78, via Curtius rearrangement. Saponification of 78 affords tranylcypromine (79). 

The thermal decomposition of ethyl diazoacetate in 9//-indcno[2,l -6]pyridine (3) effects expansion of the pyridine ring to give ethyl indeno[l,2-Z>]azepine-3-carboxylate (4), the first example of the indeno[l,2-Z>]azepine system.56... 

Huisgen et al. also studied the thermal decomposition of ethyl diazoacetate in the presence of benzonitrile and phenylacetonitrile to give the corresponding 2-substituted-5-ethoxy oxazoles 3 in variable yields (Scheme 3).<64CB2864> The authors found that the solvent had an effect on the rate of decomposition of ethyl diazoacetate in the polar solvent, niuobenzene, the rate was found to be twice that in the hydrocarbon solvent, decalin. 

Early studies into the decomposition of ethyl diazoacetate by a ic-allyl palladium chloride complex in the presence of acetonitrile led to the isolation of 2-methyl-5-ethoxyoxazole in... 

The most significant and widely studied reactivity of the ruthenium and osmium porphyrin carbene complexes is their role in catalyzing both the decomposition of diazoesters to produce alkenes and the cyclopropanation of alkenes by diazoesters. Ethyl diazoacetate is used to prepare the carbene complex 0s(TTP)(=CHC02Et)... 

The combined ether solutions are then subjected to distillation at 20° or below under the vacuum obtainable from a water pump until all the ether is removed. Prolonged distillation results in decomposition of the diazo ester and in a decreased yield. The yellow residual oil is practically pure ethyl diazoacetate and is satisfactory for most synthetic purposes (Note 3). The yield is about 98 g. (85%) (Notes 4 and 5). 

Diverging results have been reported for the carbenoid reaction between alkyl diazoacetates and silyl enol ethers 49a-c. Whereas Reissig and coworkers 60) observed successful cyclopropanation with methyl diazoacetate/Cu(acac)2, Le Goaller and Pierre, in a note without experimental details u8), reported the isolation of 4-oxo-carboxylic esters for the copper-catalyzed decomposition of ethyl diazoacetate. According to this communication, both cyclopropane and ring-opened y-keto ester are obtained from 49 c but the cyclopropane suffers ring-opening under the reaction conditions. 

As it is known from experience that the metal carbenes operating in most catalyzed reactions of diazo compounds are electrophilic species, it comes as no surprise that only a few examples of efficient catalyzed cyclopropanation of electron-poor alkeiies exist. One of those examples is the copper-catalyzed cyclopropanation of methyl vinyl ketone with ethyl diazoacetate 140), contrasting with the 2-pyrazoline formation in the purely thermal reaction (for failures to obtain cyclopropanes by copper-catalyzed decomposition of diazoesters, see Table VIII in Ref. 6). 

Based on a detailed investigation, it was concluded that the exceptional ability of the molybdenum compounds to promote cyclopropanation of electron-poor alkenes is not caused by intermediate nucleophilic metal carbenes, as one might assume at first glance. Rather, they seem to interfere with the reaction sequence of the uncatalyzed formation of 2-pyrazolines (Scheme 18) by preventing the 1-pyrazoline - 2-pyrazoline tautomerization from occurring. Thereby, the 1-pyrazoline has the opportunity to decompose purely thermally to cyclopropanes and formal vinylic C—H insertion products. This assumption is supported by the following facts a) Neither Mo(CO)6 nor Mo2(OAc)4 influence the rate of [3 + 2] cycloaddition of the diazocarbonyl compound to the alkene. b) Decomposition of ethyl diazoacetate is only weakly accelerated by the molybdenum compounds, c) The latter do not affect the decomposition rate of and product distribution from independently synthesized, representative 1-pyrazolines, and 2-pyrazolines are not at all decomposed in their presence at the given reaction temperature. 

Olefins analogous to 158 and 159 were also isolated from the CuS04-catalyzed decomposition of ethyl diazoacetate in the presence of 2-isopropenyl-2-methyl-1,3-dithiane (total yield 56%, E Z — 4 1) a butadiene was absent from the reaction mixture 161). With dimethyl diazomalonate instead of ethyl diazoacetate, only the Z-olefin resulting from a [2,3]-sigmatropic rearrangement of the corresponding sulfur ylide was obtained in 36 % yield 161). When the same procedure was applied to... 

Transition-metal catalyzed decomposition of alkyl diazoacetates in the presence of acetylenes offers direct access to cyclopropene carboxylates 224 in some cases, the bicyclobutane derivatives 225 were isolated as minor by-products. It seems justified to state that the traditional copper catalysts have been superseded meanwhile by Rh2(OAc)4, because of higher yields and milder reaction conditions217,218) (Table 17). [(n3-C3H5)PdCl]2 has been shown to promote cyclopropenation of 2-butyne with ethyl diazoacetate under very mild conditions, too 2l9), but obviously, this variant did not achieve general usage. Moreover, Rh2(OAc)4 proved to be the much more efficient catalyst in this special case (see Table 17). 

Whereas pyrrole was reported not to give N/H insertion by ketocarbenoids, such a reaction mode does occur with imidazole Copper-catalyzed decomposition of ethyl diazoacetate at 80 °C in the presence of imidazole gives ethyl imidazol- 1-ylacetate exclusively (93 %) small amounts of a C-alkylated imidazole were obtained additionally under purely thermal conditions 244). N/H insertion also takes place at benzimidazole 245 a). The reaction is thought to begin with formation of an N3-ylide, followed by N1 - C proton transfer leading to the formal N/H insertion product. Diazomalonic raters behave analogously however, they suffer complete or partial dealkoxycarbonylation under the reaction conditions 244) (Scheme 34). N-alkylation of imidazole and benzimidazole by the carbenoids derived from co-diazoacetophenone and 2-(diazoacetyl)naphthalene has also been reported 245 b>. 

Aziridines have been synthesized, albeit in low yield, by copper-catalyzed decomposition of ethyl diazoacetate in the presence of an inline 260). It seems that such a carbenoid cyclopropanation reaction has not been realized with other diazo compounds. The recently described preparation of 1,2,3-trisubstituted aziridines by reaction of phenyldiazomethane with N-alkyl aldimines or ketimines in the presence of zinc iodide 261 > most certainly does not proceed through carbenoid intermediates rather, the metal salt serves to activate the imine to nucleophilic attack from the diazo carbon. Replacement of Znl2 by one of the traditional copper catalysts resulted in formation of imidazoline derivatives via an intermediate azomethine ylide261). 

The reaction, formally speaking a [3 + 2] cycloaddition between the aldehyde and a ketocarbene, resembles the dihydrofuran formation from 57 a or similar a-diazoketones and alkenes (see Sect. 2.3.1). For that reaction type, 2-diazo-l,3-dicarbonyl compounds and ethyl diazopyruvate 56 were found to be suited equally well. This similarity pertains also to the reactivity towards carbonyl functions 1,3-dioxole-4-carboxylates are also obtained by copper chelate catalyzed decomposition of 56 in the presence of aliphatic and aromatic aldehydes as well as enolizable ketones 276). No such products were reported for the catalyzed decomposition of ethyl diazoacetate in the presence of the same ketones 271,272). The reasons for the different reactivity of ethoxycarbonylcarbene and a-ketocarbenes (or the respective metal carbenes) have only been speculated upon so far 276). 

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). 

Table 20. Yields of C/H insertion products in the Rh2(CF3COO)4-catalyzed decomposition of ethyl diazoacetate in alkanes (22 °C 100 mmol of cycloalkane or 200 mmol of acyclic alkane, 3 mmol of diazoester, 2.0-2.2 1(T3 mmol of catalyst) ...

Novel example of this reaction type are given by the copper-catalyzed decomposition of ethyl diazoacetate in the presence of bis(dialkoxyphosphoryl)disulfides 374 350 where P/S insertion sometimes accompanies the S/S insertion, and of bis(dialkoxy-thiophosphoryl)trisulfides 375 351 where desulfurization to give the disulfide derived product occurs during the reaction. Only P/S insertion product was obtained from bis(dialkoxyphosphoryl)trisulfide or -tetrasulfide 376 the copper-catalyst is dispensable in this case351K... 

The EfZ ratio of stilbenes obtained in the Rh2(OAc)4-catalyzed reaction was independent of catalyst concentration in the range given in Table 22 357). This fact differs from the copper-catalyzed decomposition of ethyl diazoacetate, where the ratio diethyl fumarate diethyl maleate was found to depend on the concentration of the catalyst, requiring two competing mechanistic pathways to be taken into account 365), The preference for the Z-stilbene upon C ClO -or rhodium-catalyzed decomposition of aryldiazomethanes may be explained by the mechanism given in Scheme 39. Nucleophilic attack of the diazoalkane at the presumed metal carbene leads to two epimeric diazonium intermediates 385, the sterically less encumbered of which yields the Z-stilbene after C/C rotation 357,358). Thus, steric effects, favoring 385a over 385 b, ultimately cause the preferred formation of the thermodynamically less stable cis-stilbene. 

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. 

Ethyl 2-fluoroethoxyacetate, F [CH2]2 0 CH2 C02Et, could not be prepared by the action of ethyl diazoacetate on pure redistilled 2-fluoroethyl alcohol, and the addition of a small quantity of concentrated hydrochloric acid had no effect, which is rather surprising in view of the known catalytic action of acids on the decomposition of the diazoacetic ester. However, fluoroethyl alcohol which had not been specially dried reacted immediately with ethyl diazoacetate with a vigorous evolution of nitrogen and the simultaneous disappearance of the yellow colour of the diazo ester. 

Hydrazine was first obtained by hydrolytic decomposition of bis-diazoacetic acid . The latter, a tetrazine derivative, is obtained from ethyl diazoacetate in the form of alkali salt by the (catalytic) action of strong alkali. Two molecules of the acid simply unite and, at the same time, the ester group is hydrolysed ... 

Like those of all the simple aliphatic diazo-compounds the manifold reactions of ethyl diazoacetate are determined by the lability of the nitrogen. The elimination of the latter is catalytically accelerated by aqueous acids, and, indeed, the velocity of decomposition is directly proportional to the hydrogen ion concentration, so that a means is provided by which this concentration can be measured for acids of... 

Experiments.—In order to learn, at least qualitatively, the influence of the hydrogen ion concentration on the velocity of decomposition, about 0-5 c.c. of ethyl diazoacetate is dissolved in a little 50 per cent alcohol and the solution is divided into two portions in small beakers to which respectively 1 c.c. of 0-1 AT-hydrochloric acid and 1 c.c. of 0-1 N-acetic acid (prepared in a measuring cylinder from glacial acetic acid) are added. 

The catalytic activity of rhodium diacetate compounds in the decomposition of diazo compounds was discovered by Teyssie in 1973 [12] for a reaction of ethyl diazoacetate with water, alcohols, and weak acids to give the carbene inserted alcohol, ether, or ester product. This was soon followed by cyclopropanation. Rhodium(II) acetates form stable dimeric complexes containing four bridging carboxylates and a rhodium-rhodium bond (Figure 17.8). 

Acceptor-substituted diazomethanes can be explosive, and low-molecular-weight diazo compounds, in particular, should be handled with care. Ethyl diazoacetate has a half-life of 109h at 100°C in inert solvents [984, p 425], but traces of acid or catalytically active salts can dramatically accelerate the thermal decomposition. Monoacyldiazomethanes are thermally less stable than diazoacetates [985], whereas bis-acceptor-substituted diazomethanes generally have high thermal and chemical stability. 

With benzo[6]furan, dichlorocarbene in cyclohexane gives an unstable addition product which, on treatment with water, yields the chromenyl ether (81 Scheme 49) (63JOC577). Decomposition of ethyl diazoacetate in the presence of benzo[6]furan yields the expected mixture of cyclopropanes. The major isomer has been cleaved under acidic conditions (Scheme 50) (77JOC3945). 

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