Dimethyl diazomalonate

Pyridinium ylide is considered to be the adduct car-bene to the lone pair of nitrogen in pyridine. The validity of this assumption was confirmed by Tozume et al. [12J. They obtained pyridinium bis-(methoxycarbonyl) meth-ylide by the photolysis of dimethyl diazomalonate in pyridine. Matsuyama et al. [13] reported that the pyridinium ylide was produced quantitatively by the transylidalion of sulfonium ylide with pyridine in the presence of some sulfides. However, in their method it was not easy to separate the end products. Kondo and his coworkers [14] noticed that this disadvantage was overcome by the use of carbon disulfide as a catalyst. Therefore, they used this reaction to prepare poly[4-vinylpyridinium bis-(methoxycarbonyl) methylide (Scheme 12) by stirring a solution of poly(4-vinylpyridine), methylphenylsulfo-nium bis-(methoxycarbonyl)methylide, and carbon disulfide in chloroform for 2 days at room temperature. 

Kondo maintained his interest in this area, and with his collaborators [62] he recently made detailed investigations on the polymerization and preparation of methyl-4-vinylphenyl-sulfonium bis-(methoxycarbonyl) meth-ylide (Scheme 27) as a new kind of stable vinyl monomer containing the sulfonium ylide structure. It was prepared by heating a solution of 4-methylthiostyrene, dimethyl-diazomalonate, and /-butyl catechol in chlorobenzene at 90°C for 10 h in the presence of anhydride cupric sulfate, and Scheme 27 was polymerized by using a, a -azobisi-sobutyronitrile (AIBN) as the initiator and dimethylsulf-oxide as the solvent at 60°C. The structure of the polymer was confirmed by IR and NMR spectra and elemental analysis. In addition, this monomeric ylide was copolymerized with vinyl monomers such as methyl methacrylate (MMA) and styrene. 

Much of the early work into the rhodium(II)-catalysed formation of oxazoles from diazocarbonyl compounds was pioneered by the group of Helquist. They first reported, in 1986, the rhodium(II) acetate catalysed reaction of dimethyl diazomalonate with nitriles.<86TL5559, 93T5445, 960S(74)229> A range of nitriles was screened, including aromatic, alkyl and vinyl derivatives with unsaturated nitriles, cyclopropanation was found to be a competing reaction (Table 3). 

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 preference for the less substituted double bond also determines the outcome of the copper-catalyzed cyclopropanation of isotetraline with dimethyl diazomalonate which gives 27 and its dehydrogenated relative 2883) the same behavior of the carbenoid derived from ethyl diazoacetate has been reported 84). 

Allyl acetals154). Allyl ethers give no or only trace amounts of ylide-derived products in the Rh2(OAc)4-catalyzed reaction with ethyl diazoacetate, thus paralleling the reactivity of allyl chloride. In contrast, cyclopropanation must give way to the ylide route when allyl acetals are the substrates and ethyl diazoacetate or dimethyl diazomalonate the carbenoid precursors. 

In addition to cyclopropane 145 and the expected [2,3] rearrangement product 143 of an intermediary oxonium ylide, a formal [1,2] rearrangement product 144 and small amounts of ethyl alkoxyacetate 146 are obtained in certain cases. Comparable results were obtained when starting with dimethyl diazomalonate. Rh2(CF3COO)4 displayed an efficiency similar to Rh2(OAc)4, whereas reduced yields did not recommend the use of Rh6(CO)16 and several copper catalysts. Raising the reaction temperature had a deleterious effect on total product yield, as had... 

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... 

Some functionalized thiophenes have been investigated in order to assess the scope of ylide-derived chemistry. As already mentioned, 2-(hydroxymethyl)thiophene still gives the S-ylide upon Rh2(OAe)4-catalyzed reaction with dimethyl diazomalonate 146 but O/H insertion instead of ylide formation seems to have been observed by other workers (Footnote 4 in Ref. 2S4)). From the room temperature reaction of 2-(aminomethyl)thiophene and dimethyl diazomalonate, however, salt 271 was isolated quite unexpectedly 254). Rh2(OAc)4, perhaps deactivated by the substrate, is useless in terms of the anticipated earbenoid reactions. Formation of a diazo-malonic ester amide and amine-catalyzed cyclization to a 5-hydroxytriazole seem to take place instead. 

A thermally stable sulfonium ylide is also obtained from the CuS04-catalyzed reaction between dimethyl diazomalonate and thioxanthene or its 9-alkyl derivatives 339 > rearrangement to the thioxanthen-9-ylmalonate occurs only with base catalysis. 

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

The direct photolysis of dimethyl diazomalonate in 2-butyne afforded the cyclopropene (276), but sensitization of the photolysis with benzophenone gave the furan (277) in 43% yield (Scheme 73) (71JA6337). Thermal rearrangement of 2,2-dimethoxycarbonylmethyl-enecyclopropane to 2-methoxy-3-methoxycarbonyl-4-methylfuran was observed, a reac-... 

The products formed in these reactions are very sensitive to the functionality on the carbenoid. A study of Schechter and coworkers132 using 2-diazo-1,3-indandione (152) nicely illustrates this point. The resulting carbenoid would be expected to be more electrophilic than the one generated from alkyl diazoacetate and consequently ihodium(II) acetate could be used as catalyst. The alkylation products (153) were formed in high yields without any evidence of cycloheptatrienes (Scheme 33). As can be seen in the case for anisole, the reaction was much more selective than the rhodium(II)-catalyzed decomposition of ethyl diazoacetate (Scheme 31), resulting in the exclusive formation of the para product. Application of this alkylation process to the synthesis of a novel p-quinodimethane has been reported.133 Similar alkylation products were formed when dimethyl diazomalonate was decomposed in the presence of aromatic systems, but as these earlier studies134 were carried out either photochemically or by copper catalysis, side reactions also occurred, as can be seen in the reaction with toluene (equation 36). 

The reaction of N-alkylated pyrroles with carbenoids leads exclusively to substitution products. Due to the pharmaceutical importance of certain pyrrolylacetates, the reaction with alkyl diazoacetates (Scheme 45) has been systematically studied using about 50 different catalysts.13 Both the 2- and 3-alkylated products (216) and (217) could be formed and the ratio was dependent on the size of the JV-alkyl group and ester and also on the type of catalyst used. This has been interpreted as evidence that transient cyclopropane intermediates were not involved because if this were the case, the catalyst should not have influenced the isomer distribution. Instead, the reaction was believed to proceed by dipolar intermediates, whereby product control is determined by the position of electrophilic attack by the carbenoid. Similar alkylations with dimethyl diazomalonate gave greater selectivity and yields.164... 

The reaction of dimethyl diazomalonate with an excess of benzaldehyde with or without metal catalyst furnished the diastereomeric 1,3-dioxolanes (156) and the oxirane (155 Scheme 35). The reaction was proposed to proceed via the intermediacy of a carbonyl ylide dipole.135 Benzaldehyde plays a double role... 

Thiepine 96 was reacted with dimethyl diazomalonate 97a and dibenzyl diazomalonate 97b in the presence of 5% [Rh2(OAc)4] to give ylides 98a and 98b in 75% and 63% yields, respectively (Equation 11) <20060BC2218>. 

Only a limited number of examples have been reported. The reactivity of sulfonium ylide 98a, prepared by the reaction of thiepine 96 and dimethyl diazomalonate (Section 13.03.6.1), was examined <20060BC2218>. The reactivity of the stabilized sulfonium ylide 98a was restricted to the highly reactive Michael acceptor, tetracya-noethylene 152 (the ylide failed to react with benzaldehyde or dicyanoethylene). Reaction of ylide 98a with tetracyanoethylene 152 led to the consumption of the ylide 98a (Equation 22). Thiepine 96 was produced in the reaction and the formation of cyclopropane 153 was suggested. 

Thiopyranylindole 236 underwent ylide-derived Stevens rearrangements when exposed to malonate and cr-ketoester carbenoids and resulted in a one-carbon ring expansion reaction to lead to thiepines <2005JOC746>. Thus, reaction of thiopyranylindole 236 with dimethyl diazomalonate and /-butyl diazoacetylacetate in the presence... 

Copper-catalyzed cyclopropanation of 4,7-dihydro-l,3-dioxepin 46a with ethyl diazoacetate gave cyclopropanodiox-epane 49, as the only product. The product formation of cyclopropanation with dimethyl diazomalonate (dmdm) catalyzed by copper(n) acetylacetonate depends on the substitution pattern of the dioxepin (Scheme 3) <2000HCA966>. 

Dihydro-l,3-dioxepin 47b reacted with dimethyl diazomalonate in a double [3+2] cycloaddition reaction to give furofuran derivative 54 as a mixture of stereoisomers (Scheme 4) <2000HCA966>. 

A recent synthesis of 1 by Ganem et al.2 uses dimethyl diazomalonate for introduction of the enol pyruvate side chain. 

Dimethyl diazomalonate undergoes reaction with nitriles in the presence of rhodium(II) acetate to give 2-substituted-4-carbomethoxy-l,3-oxazoles (255). The reaction proceeds with a wide range of nitriles,133-139 although cyclopropanation is a competing process in the case of unsaturated nitriles.129... 

Reaction of the enol ether 58 with dimethyl diazomalonate provides the spiro compound 59 in high yield. Reduction and acid catalyzed cyclopropane cleavage gives the unsaturated y-lactol 60 which can be oxidized to p-methylene y-butyro-lactone 61 20). 

Photolysis of pyrazoles such as (64) has also been shown to produce indenes as well as cyclopropenes. The indene is apparently derived from a triplet intermediate, while the cyclopropene is singlet derived 54). In a related example, direct photolysis of dimethyl diazomalonate in an alkyne leads to moderate yields of cyclopropene, whereas sensitized photolysis leads to furans by ring closure of an intermediate diradical (65) 55). 

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