Diazoacetates 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). 

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 diazo transfer reaction between p-toluenesulfonyl azide and active methylene compounds is a useful synthetic method for the preparation of a-diazo carbonyl compounds. However, the reaction of di-tert-butyl malonate and p-toluenesulfonyl azide to form di-tert-butyl diazomalonate proceeded to the extent of only 47% after 4 weeks with the usual procedure." The present procedure, which utilizes a two-phase medium and methyltri-n-octylammonium chloride (Aliquat 336) as phase-transfer catalyst, effects this same diazo transfer in 2 hours and has the additional advantage of avoiding the use of anhydrous solvents. This procedure has been employed for the preparation of diazoacetoacetates, diazoacetates, and diazomalonates (Table I). Ethyl and ten-butyl acetoacetate are converted to the corresponding a-diazoacetoacetates with saturated sodium carbonate as the aqueous phase. When aqueous sodium hydroxide is used with the acetoace-tates, the initially formed a-diazoacetoacetates undergo deacylation to the diazoacetates. Methyl esters are not suitable substrates, since they are too easily saponified under these conditions. 

Fig. 10.9. Computed transition structure for addition of methyl phenyl-diazoacetate to styrene from B3LYP/6-31G /LANL2DZ computations. Reproduced from J. Am. Chem. Soc., 125, 15902 (2003), by permission of the American Chemical Society. 

It is interesting to compare this case to the reaction of ethyl diazoacetate with chiral methyl-1-naphthylphenylsilane, which proceeds with at least 95% retention of configuration 61). 

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. 

For the synthesis of permethric acid esters 16 from l,l-dichloro-4-methyl-l,3-pentadiene and of chrysanthemic acid esters from 2,5-dimethyl-2,4-hexadienes, it seems that the yields are less sensitive to the choice of the catalyst 72 77). It is evident, however, that Rh2(OOCCF3)4 is again less efficient than other rhodium acetates. The influence of the alkyl group of the diazoacetate on the yields is only marginal for the chrysanthemic acid esters, but the yield of permethric acid esters 16 varies in a catalyst-dependent non-predictable way when methyl, ethyl, n-butyl or f-butyl diazoacetate are used77). 

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. 

The change in selectivity is not credited to the catalyst alone In general, the bulkier the alkyl residue of the diazoacetate is, the more of the m-permethric acid ester results 77). Alternatively, cyclopropanation of 2,5-dimethyl-2,4-hexadiene instead of l,l-dichloro-4-methyl-l,3-pentadiene leads to a preference for the thermodynamically favored trans-chrysanthemic add ester for most eatalyst/alkyl diazoacetate combinations77 . The reasons for these discrepandes are not yet clear, the interplay between steric, electronic and lipophilic factors is considered to determine the stereochemical outcome of an individual reaction77 . This seems to be true also for the cyclopropanation of isoprene with different combinations of alkyl diazoacetates and rhodium catalysts77 . 

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). 

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). 

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... 

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. 

In the presence of catalytic amounts of 207a and at moderate temperatures (—15 to +30 °C), the cyclopropanes derived from styrene and various alkyl diazoacetates were obtained in good yields (80-95 %) with remarkably high enantiomeric excess for both the cis(lS, 2R) and the transilS, 2S) isomer. With increasing steric bulk of the rater substituent (methyl -> neopentyl), both the trans/cis ratio (0.69 - 2.34) and the optical yield (61 ->88% for the /raws-cyclopropane at 0 ° ) became higher 88,95). 

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.

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