Diethyl diazoacetate

P-Keto esters have been prepared in moderate to high yields by treatment of aldehydes with diethyl diazoacetate in the presence of a catalytic amount of a Lewis acid such as SnCL, BF3, or GeCL. The reaction was successful for both aliphatic and aromatic aldehydes, but the former react more rapidly than the latter, and the difference is great enough to allow selective reactivity. In a similar process, aldehydes react with certain carbanions stabilized by boron, in the presence of (F3CC0)20 or NCS, to give ketones. 

For the study of the cyclopropanation reaction of indoles with diethyl diazoacetate (EDA), we were inspired by the pioneering work of Welstead [63] and Wenkert [64], They found that the deactivation of the indole nucleus, through electron-withdrawing substituents at Nl, allows the addition of carbene moiety into the 2,3-double bond without the competitive rearrangement that leads to the C-H insertion product (Scheme 4.16). 

Table 4.2 Cyclojaopanation of indole III-39 with diethyl diazoacetate...

Etliyl diazoacetate has been prepared from sodium nitrite luid ethyl glycinatc hydrochloride in the presence of diethyl filler. The present [irocedure utilizes the unique ability of... 

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). 

EvenPd(OAc)2 is not effective in catalyzing the cyclopropanation of a,P-unsaturated nitriles by ethyl diazoacetate. Instead, vinyloxazoles 92 are formed from acrylonitrile or methacrylonitrile by carbenoid addition to the CsN bond 143 Diethyl maleate and diethyl fumarate as well as polyketocarbenes are by-products in these reactions the 2-pyrazoline which would result from initial [3 + 2] cycloaddition at the C=C bond and which is the sole product of the uncatalyzed reaction at room temperature, can be avoided completely by very slow addition of the diazoester... 

In contrast to ethyl diazoacetate, diethyl diazomalonate reacts with allyl bromide in the presence of Rh2(OAc)4 to give the ylide-derived diester favored by far over the cyclopropane (at 60 °C 93 7 ratio). This finding bespeaks the greater electrophilic selectivity of the carbenoid derived from ethyl diazomalonate. For reasons unknown, this property is not expressed, however, in the reaction with allyl chloride, as the carbenoids from both ethyl diazoacetate and diethyl diazomalonate exhibit a similarly high preference for cyclopropanation. 

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... 

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. 

Copper(ll) acetylacetonate Copper, bis(2,4-pentanedionato-0,0 )- (9) (46369-53-3) Methyl diazoacetate Acetic acid, diazo-, methyl ester (8,9) (6832-16-2) Triethylammonium fluoride Triethylamine hydrofluoride (8) Elhanamine, N,N-diethyl-, hydrofluoride (9) (29585-72-6)... 

Ethyl diazoacetate condenses with diethyl malonate to yield a derivative of 4-hydroxypyrazole (Bertho and Niissel, Annalen, 1927, 457, 278) ... 

Ethyl diazoacetate, as source of car-bethoxycarbene, 50, 94 Ethylene, with p-methoxyphenyl-acetyl chloride and aluminum chloride to give 6-methoxy- 3-tetralone, 51,109 Ethyl hydrazinecarboxylate, from hydrazine hydrate and diethyl carbonate, 51,121 Ethylidenecyclohexylamine, 50,66 Ethyl 1-iodopropionate, from ethyl... 

A plausible reaction mechanism for this reaction was proposed by the authors. The Cu(i) carbene 182 generated from ethyl diazoacetate and the chiral Gu(i) complex can either react with another molecule of ethyl diazoacetate to form a mixture of diethyl maleate and fumarate 183, or with the imine lone pair to form a Gu(i)-complexed azomethine ylide... 

Cyclopropanation.2 This metal carbonyl cluster is an effective catalyst for cyclo-propanation of alkenes with ethyl diazoacetate. Minor by-products are diethyl maleate and fumarate, but products of allylic C -H insertion are not formed. The yield of the cyclopropane can be increased if the ethyl diazoacetate is added slowly over a period of 6 hours to the olefin and catalyst. Under these conditions yields of eyclopropanes are 85 -90%. 

The reaction of ethyl diazoacetate (312) with sodium or potassium ethoxide was studied by Curtius and his coworkers (08CB3140). They isolated a compound for which they proposed structure (316), which is a metal salt of diethyl l,6-dihydro-l,2,4,5-tetrazine-3,6-dicarboxy-late complexed with one mole of the ethoxide used. 

The reaction of Ru(TMP) with ethyl diazoacetate yielded a carbene complex, e.g. Ru(CHC02Et)(TMP) [316], An excess of the diazo compound led to catalytic formation of cis- and trans diethyl maleate in an unexpected ratio of 15 1. The nucleophilic ethyl diazoacetate is proposed to attack the electrophilic carbene complex and produce an intermediate betaine-line species which eliminates both Ru(TMP) and N2 to form the maleates. Similar reactions were observed with Os(TTP) complexes [313a], These reactions are reminiscent of the above-mentioned lability of a putative methyleneruthenium porphyrin. 

Asymmetric cyclopropanation. Three laboratories have reported that copper complexes of chiral bis(oxazolines) are effective catalysts for asymmetric cyclopropanation of alkenes with diazoacetates. Bis(oxazolines) such as 1 are readily available by condensation of a-amino alcohols with diethyl malonate followed by cyclization, effected with dichlorodimethyltin or thionyl chloride. Cyclopropanation of styrene with ethyl diazoacetate catalyzed by copper complexes of type 1 indicates... 

A complication in aziridination is that metal carbenoids can react directly with some imines to yield aziridines. Fortunately, imines bearing electron-withdrawing groups are less reactive to carbenoids and more reactive to ylides than electron-rich imines. Thus, N-tosyl, N-diphenylphosphinyl and N-[-(tri-methylsilyl)ethansulfonyl] imines (-(trimethylsilyl)ethansulfonyl = SES) were all suitable substrates using dimethylsulfide and Rh2(OAc)4, with no background reaction detected [77, 78]. Phenyldiazomethane, N,N-diethyl diazoacetamide and ethyl diazoacetate could be used as the diazo component, although the latter two required temperatures of 60 °C to decompose. 

Having demonstrated the feasibility of their catalytic process, Aggarwal and colleagues explored the use of a chiral sulfide, 12 [77, 78]. It was found that N-SES benzaldimines yielded aziridines 18a-e in excellent enantioselectivity (up to 97% ee), albeit in moderate yield and diastereoselectivity (transicis 3 1—5 1). At catalytic loadings of 12 (20 mol%), Rh2(OAc)4 gave slightly better yields and ee-values than Cu(acac)2 in most cases. The use of alternative diazo compounds such as N,N-diethyl diazoacetamide and ethyl diazoacetate provided moderate enantioselectiv-ities at best, and only stoichiometric sulfide loadings were reported. 

Dialkyl phosphines Diazoacetic ester Diazoamidobenzol Diazobenzene chloride Diethyl carbonate Diisopropyl higher alkyl ethers Ferrous perchlorate... 

Racemic cyclopropanation reactions have been performed with rhodium1 241 and palladium11251 catalysts. The reaction between an olefin and ethyl diazoacetate in the presence of 1 mol% Rh2(OAc)4 in [C4Ciim][PF6] proceeded with higher rates, improved yields and better trans-selectivity relative to conventional solvents for both electron-rich and electron-deficient styrene derivatives. The product was obtained by extraction with diethyl ether and in this manner only trace amounts of the catalyst were leached from the ionic liquid. Nevertheless, yields drop from 88% in the first run to 72% in the fifth run. 

Aziridines have been synthesised in ionic liquids from diazoacetate and mimes.[1271 The copper-mediated aziridination between N-(p-tolylsufonyl)imino]phenyliodinane and an excess of olefin proceeded in good yield at room temperature (Scheme 9.32).[128] In most cases, the reaction progressed considerably faster in the ionic liquid than in acetonitrile. No marked differences were observed between the reaction rates in [C4Ciim][BF4] and [C4Ciim][PF6]. After extraction with diethyl ether, the... 

Unsaturated acetals. Reaction of ethyl diazoacetate with dimethyl acetals of a,(3-unsaturated aldehydes catalyzed by BE, ethciate gives as the main product acetals of P. y-unsaturated aldehydes by a carbon-carbon insertion. A similar reaction with ketals gives a complex mixture. The reaction is less selective with diethyl acetals. 

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