Monosubstituted malonic

The monosubstituted malonic ester still possesses an activated hydrogen atom in its CH group it can be converted into a sodio derivative (the anion is likewise mesomeric) and this caused to react with an alkyl halide to give a C-disubstituted malonic ester. The procedure may accordingly be employed for the synthesis of dialkyImalonic and dialkylacetic acids ... 

Two general methods can be used, the choice depending on whether the parent ester is a dialkyl- or a monoalkylacetate. Many functional variations can be tolerated, including monosubstituted malonates, and y- and (5-lactones (5). 

Allenic halides can also react with monosubstituted malonates to afford 2-(l, 2 -allenyl)malonates 128 and 131. With an unsubstituted malonate the migration of the C=C bond was observed to form 1,3-dienes 129 and 130 [65]. 

From 2-amino-6-methylpyridine and monosubstituted malonates Buu Hoi and Declerq100 obtained 3-substituted 1,8-naphthyridines of type 66, and from 2-aminopyridine they obtained 3-substituted pyrido[l,2- ]pyrimidines of type 63 (R = H). 

The synthetic utility of alkylation of enolates is utilized in the syntheses of malonic ester (3.3) and acetoacetic ester (3.2). For example, carbanion generated from malonic ester undergoes an Sn2 reaction with alkyl halide to yield alkyl-substituted malonic ester. The monosubstituted malonic ester still has an active hydrogen atom. The second alkyl group (same or different) can be introduced in a similar manner. Acid-catalyzed hydrolysis or base-catalyzed hydrolysis of mono- or disubstituted derivative of malonic ester followed by acidification gives the corresponding mono- or disubstituted malonic acid, which on decarboxylation yields the corresponding monocarboxylic acid (Scheme 3.3). 

The thermal decomposition of disubstituted malonic anhydrides gives ketoketenes, R,C = C = 0. A similar synthesis of an aldoketene, RHC=C=0, from a monosubstituted malonic anhydride has never been accomplished. 

A further example is the zinc stearate-catalyzed addition of malonic ester derivatives to acetylene. The reaction also takes place with monosubstituted malonic esters [46]. C-vinyl malonic esters have found an application, for example, in the synthesis of barbiturates. 

Derivatives of malonic acid convert phenols into coumarins malonyl chloride at ambient temperature and with titanium(IV) chloride leads to a 4-hydroxycou-marin [2283] whereas pyridinols condense with monosubstituted malonic esters... 

Chiral malonate esters have been used successfully in asymmetric cyclopropanations, as shown by the example in Scheme 6.39, part of a total synthesis of steroids such as estrone [143,144]. The key step in this sequence is an intramolecular Sn2 alkylation of the monosubstituted malonate. The rationale for the diastereoselec-tivity is shown in the illustrated transition structure. Note that the enolate has C2 symmetry, so it doesn t matter which face of the enolate is considered. The illustrated conformation has the ester residues syn to the enolate oxygens to relieve Al>3 strain, with the enolate oxygens and the carbinol methines eclipsed. The allyl halide moiety is oriented away from the dimethylphenyl substituent, exposing the alkene Re face to the enolate. The crude selectivity is about 90% as determined by conversion to the dimethyl ester and comparison of optical rotations [143], but a single diastereomer may be isolated in 67% yield by preparative HPLC [144], This reaction deserves special note because it was conducted on a reasonably large scale ... 

Dialkylmalonic acids. Dianions of carboxylic acids have been prepared using LDA in THF-HMPT (4,301-302). Krapcho reports that trianions (2) of monosubstituted malonic acids (1) can be prepared with 3 equiv. of n-butyl-lithium in THF at 0°. These can be alkylated by primary halides to give dialkylmalonic acids (3). Alkylation cannot be achieved with secondary halides. This procedure is not applicable to malonic acid itself. 

Oxidatively generated electrophilic malonyl radicals react regiospecifically with thiophene to form (2-thienyl)malonic ester <88H(27)2627>. Treatment of thiophene with cerium(IV) sulfate and an excess of dimethyl malonate in methanol at room temperature yields 2-thienylmalonic ester in 85% yield. In this case, the initially formed cr-radical is oxidized by the cerium(IV) sulfate. 2-Methylthiophene similarly gives the 5-malonyl-substituted product. Benzo[i]thiophene leads to the 2-malonyl-benzo[Z)]thiophene in 41% yield. Monosubstituted malonates could also be used in this reaction. Thiophene and 2-acetylthiophene react with triethyl methanetricarboxylate in the presence of Mn(III) to form the corresponding thienylmethane tricarboxylic esters. Yields are about 55% <91S567>. 

Nickel. The kinetics have been reported for the reaction of Ni q with the un-protonated and monoprotonated forms of dimethyl- and di-n-butyl-malonic acids (see Table 5). For the dimethyl derivative the results are similar to those previously found for some monosubstituted malonic acids except that the chelate-ring-opening rate is enhanced as a consequence of the increased steric hindrance between the two methyl groups. However, ring-opening is faster with dimethylmalonate k = 1.5 x... 

Monosubstituted malonic anhydrides have not yielded aldoketenes, but malonic acid itself jdelds carbon suboxide when heated with phos-pho] pentoxide. ... 

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