Methyl diazoacetate

Since 1,3-dipolar cycloadditions of diazomethane are HOMO (diazomethane)-LUMO (dipolarophile) controlled, enamines and ynamines with their high LUMO energies do not react (79JA3647). However, introduction of carbonyl functions into diazomethane makes the reaction feasible in these cases. Thus methyl diazoacetate and 1-diethylaminopropyne furnished the aminopyrazole (620) in high yield. 

Thus, insertion of methoxymethylcarbene in the C—H bond of a furazan occurred on thermolysis of 1 or 5 with methyl diazoacetate in the presence of copper stearate to give methoxycarbonyImethyIfurazans 39 in 9-12% yields (89BAU2640, 89IZV2876) (Scheme 13). 

Komendantov et al. found that thermal decomposition of methyl diazoacetate in the presence of benzonitrile yielded two products.<73JOU431> One is the expected 2-phenyl-5-methoxyoxazole 4 in about 35% yield and the other product was methyl 3-phenyl-2//-azirine-2-carboxylate 5 in around 1% yield (Scheme 4). 

The thermal [1] or photochemical [5] isomerization of N-silylated allylamine in the presence of Fe(CO)5 provides the corresponding N-silylated enamines 7a and 7b. Z-enamine 7b does not react in any of the examined cycloadditions. The cyclopropanation of E-enamine 7a with methyl diazoacetate under copper(I) catalysis provides the donor-acceptor-substituted cyclopropane 9 [1], which can be converted in good yield into the interesting dipeptide 10 [6]. 

EDA = ethyl diazoacetate MDA = methyl diazoacetate OTf = 03SCF3 (trifluoro-methanesulfonate) acac = acetylacetonate hfacac = hexafluoroacetylacetonate. 

Diastereofacial differentiation occurs upon cyclopropanation of the substituted oyclohexene 43 with methyl diazoacetate. Only the two stereoisomers endo-44 and exo-44 were found, both with a 5-anti methyl group 60). In contrast, the ring substituents in l-trimethylsiloxy-cyclohexenes 45 and 46 are not efficient for such a differentiation, so that the four possible diastereomers are actually formed. 

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. 

Table 12, Asymmetric cyelopropanation by 195a-catalyzed decomposition of /-methyl diazoacetate in olefins8-b...

From a variety of differently substituted compounds, best results were obtained with the catalysts 195a-c in combination with /-methyl diazoacetate and monoolefins, cyclopropanes were obtained with a relatively high trans/cis ratio and enantiomeric excesses of 44-89% (Table 12). The absolute configuration at the catalyst s chiral center determines the enantioselectivity for both diastereoisomers. 

Under the catalytic action of Rh2(OAc)4, formation of a propargylic ether from a terminal alkyne (229, R1=H) is preferred as long as no steric hindrance by the adjacent group is felt162,218>. Otherwise, cyclopropenation may become the dominant reaction path [e.g. 229 (R1 = H, R2 = R3 = Me) and methyl diazoacetate 56% of cyclopropene, 36% of propargylic ether162)], in contrast to the situation with allylic alcohols, where O/H insertion is rather insensitive to steric influences. 

Scheme 31. Isomer distribution [%] of Rh CFjCOO -catalyzed cyclopropanation of substituted benzenes with methyl diazoacetate at 22 °C. The numbers refer to the percentage of 1,3,5-cyelohepta-triene-7-carboxylate from the total cycloheptatriene isomers.

Contrary to P-lactams, N/H insertion is only a minor process in the copper-catalyzed reaction between 2-pyrrolidinone and methyl diazoacetate. With pyrro-lidine-2-thione, this process does not take place at all. For 2-piperidinone, N/H insertion seems to be easier, but once again, the corresponding thione fails to produce such an insertion product (Scheme 35) 322),... 

The carbene moieties of methyl diazoacetate 353), dimethyl diazomalonate 3S3) and diazomethane 3541 have been inserted into the Se—Se bond of diaryl diselenides. 

Methyl diazoacetate is also decomposed on Raney nickel to give quantitatively a mixture of dimethyl fumarate and maleate 369) N2 evolution is observed even at room temperature. Most remarkably, dimethyl maleate is formed with high stereoselectivity (at 70 °C 92% of dimethyl maleate, 7% of dimethyl fumarate 370)). This represents one of the few cases of stereoselective synthesis on metal surfaces which have been found so far. 

Methyl diazoacetate was obtained according to a procedure for ethyl diazoacetate (Searle, N.E. Org. Synth., Coll. Vol. A/1963, 42). Although the experiments were usually performed with distilled methyl diazoacetate (bp 43°C at 25 mm, bath temperature below 60°C) without any problems, the cyclopropanation reaction described works equally well with undistilled diazo compound. If distilled diazo compound is desired, the submitters have stated that "a spatula of K2CO3 Is added to the crude diazo ester to trap traces of add and then distill behind a safety shield . The checkers did not evaluate this aspect of the procedure. 

Crude methyl diazoacetate contains up to 20% of the solvent dichloromethane. which has to be taken into account when calculating the stoichiometry. The checkers had no problems in preparing, handling, antf using undistilled methyl diazoacetate however, it must be emphasized that this compound is a potential explosive and all operations should be performed behind an effident safety shield. 

It the solution of methyl diazoacetate is dropped through the condenser the diazo compound is further diluted by the refluxing solvent. This simple technique diminishes formation of dimethyl lumarate and dimethyl maleate as side products. 

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)... 

Isomeric tetrahydrofuran derivatives (47 and 48) are formed by copper(II)-catalyzed decomposition of methyl diazoacetate in 2-phenyloxetan (Scheme 62).99 Use of the chiral homogeneous catalyst, bis[N-(i )-a-phenylethylsali-cylaldiminato]copper(II) (49),100 causes asymmetric induction albeit with... 

Similarly, tri-O-benzyl-glucal affords the corresponding manno-configurated methoxycarbonyl cyclopropanes upon treatment with methyl diazoacetate under... 

Ethyl diazoacetate, 1503 Ethyl 4-diazo-l,2,3-triazole-5-carboxylate, 1853 Lithium diazomethanide, 0379 3-Methoxy-2-nitrobenzoyldiazomethane, 3124 Methyl diazoacetate, 1138... 

Photolysis of diazomethane in carbon-tetrachloride in the presence of benzophenone yields 1,1,1,2-tetrachloroethane showing an enhanced absorption due to the triplet carbene. The direct photolysis of diazomethane proceeds via singlet methylene CIDNP-studies of the photolysis of methyl-diazoacetate, for which a radical pair mechanism was suggested, were recently challenged 2). 

Carbenes, such as that formed by the photolysis of methyl diazoacetate, may add to one of the carbon-carbon bonds (Scheme 6.28). 

If the C=N function is attached to an electron-withdrawing group, 1,3-dipolar cycloaddition with diazoalkanes occurs leading to 1,2,3-triazoles (5, 276). When diazomethane is used, the initially formed NH-triazole is not isolated due to a rapid subsequent NH deprotonation followed by N-methylation. Consequently, a mixture of the three Wmethyltriazoles is formed when methyl cyanoformate (71) (216) or trichloroacetonitrile (276) (217) is treated with excess diazomethane (Scheme 8.51). Huisgen and co-workers found that methyl diazoacetate reacts with TCNE by a 1,3-dipolar cycloaddition at the C=C bond and not, as published earlier by other authors, at one of the nitrile functions (72). 

Silyl enol ethers can also be used in the cyclopropanation reaction. Reissig showed that the reaction between methyl diazoacetate 53 and various enol ethers 52a-c using bu-box ligand 3 proceeded in moderate yields, as shown in Table 9.5 (Fig. 9.17fl), with trans/cis ratios up to 97 3 and ee between 32 and 49%. Pfaltz showed that cyclic enol ethers can be used as well." Cyclopentenyl enol ether 55 proceeded with methyl diazoacetate 53 and bu-box ligand 3 to afford the cyclopropanation products in 56% yield, a trans/cis ratio of 27 73, trans ee of 87% and cis ee of 92% (Fig. 9.11b, p. 544). 

Cycloaddition between the enamine 26 (Scheme 10) and ethyl diazoacetate in ethanol gave a mixture of the pyrazoline 27 and the diazo ester 29. The former was converted to the 3//-pyrazoIe 30 by chromatography on alumina or by distillation.85 Use of methyl diazoacetate in boiling chloroform gave, in contrast, a high yield of 28, convertible almost quantitatively to 31 by chromatography on silica.86 Other enamines gave l//-pyrazoIes. 

A number of 2-acyI-l-chIoroethenes add to DPD in ether, losing HC1 spontaneously from the intermediate pyrazolines, and giving l/f-pyrazoles from rearrangement of the transient 3H isomers.50,60 The acid chloride 36 gives a small amount of a 3//-pyrazoIe 37 from reaction with two moles of methyl diazoacetate (Scheme 12).88... 

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