Dimethyl dimethylmalonate

Metal reduction of malonates. Dimethyl dimethylmalonate (1) is reduced by sodium dispersed in xylene containing trimethylchlorosilane (TMCS) to dimethyl-ketene methyl trimethylsilyl acetal (2)4 ... 

Diimidazolides of dicarboxylic acids react with hydrazines in a 1 1 molar ratio to form cyclic hydrazides e.g., the diimidazolide of 2,2-dimethylmalonic acid and phenyl-hydrazine affords 1-phenyl-4,4-dimethyl-3,5-dioxopyrazolidine in 67% yield ... 

The preparation of ketenes has been discussed by Hanford and Sauer in Organic Reactions Dimethylketene has been prepared by the treatment of a-bromoisobutyryl bromide with zinc,3 and by the pyrolysis of isobutyrylphthalimide,4 dimethylmalonic anhydride,6 or a-carbomethoxy-a,j3-dimethyl- -butyrolactone. Dimethylketene dimer has been prepared by heating isobutyryl chloride with a tertiary amine. Pyrolysis of the dimer yields dimethylketene.7... 

Other alkylation reactions are observed in the condensation of cyclo-propanium ions (generated in situ) with ketones 89.92)> enamines6, nitroalkanes 93>, dimethylmalonate 92>, and phenol. 92> Thus, 7-hydroxy-7-pyrrolidinobicyclo[4.1.0]heptane (56) as well as the 7,7-dipyrrolidino derivative (54) react with acetone to give the amino ketone 113. 89> This reaction may be pictured as an addition of the enol form of the ketone to the reactive iminium salt formed from the carbinol amine. In like manner, phenol undergoes ortho substitution with the carbinol amine 114 formed from cyclopropanone and dimethyl amine. 

The reactions were carried out using [Pd(/j -C3H5)Cl]2 as procatalyst in a mixture of dimethylmalonate, N,0-bis(trimethylsilyl)acetamide (BSA), and potassium acetate in methylene chloride (eq 2) Under these conditions (5)-dimethyl 1,3-diphenylprop-2-enylmalonate was isolated in 92% yield and 91% enantioselectivity. The stereochemical outcome was rationalized by reaction through transition state A, in which the nucleophile attacks the allylic terminus trans to the oxazoline nitrogen. 

Kimura and coworkers tried to shorten the extended reaction times required for these cyclization reactions by using more reactive derivatives of malonic acid. They reacted the diazide derivative of a,a-dimethylmalonic acid with l,9-diamino-3,7-diazanonane in chloroform for 12 hr at 0°C to give the dimethyl-[14]N4 macrocycle in a 23% yield (Kimura et al., 1989a). This method will probably not be widely accepted because diazides are not safe... 

Activated methylene compounds such as dimethyl malonate have found substantial utility in palladium catalyzed allylic substitution reactions. Accordingly, the Krapcho decarboxylation is often used in conjunction with these reactions. As an example, the first total synthesis of enantiomerically pure (-)-wine lactone has utilized the sequence of reactions.27 First, the allylic substitution reaction of 2-cyclohexen-l-yl acetate (49) with alkali sodium dimethylmalonate yielded 51 with high enantioselectivity, as a result of the use of chiral phosphine ligand 50. The malonate was then subjected to Krapcho decarbomethoxylation using NaCl, H2O, and DMSO at 160 °C to yield 52. This reaction has been used similarly following the allylic substitution reaction with other malonate derivatives.28-30... 

D-A reactions, comprising st-DNA and the Cn " complex of 4,4 -dimethyl bipyridine. Nitromethane and dimethyl malonate, both of which enolize readily, were employed as the nncleophiles. With 100 equivalents of dimethyl malonate, a clean and quantitative conversion into the Michael addnct was observed after 3 days, with an ee of 91%. The addition of nitromethane was slower nsing 1000 equivalents 97% conversion and an ee of 85% were obtained in the same time. The snbstrate scope proved to be broad a series of derivatives of the snbstrate were tested in the Michael reaction and generally gave high conversions (typically > 75%) and ees (86-99% with dimethylmalonate as the nncleophile, and 82-94% with nitromethane as the nncleophile). Only in the case of the Michael addition to the enone with R = Me instead of aryl, did the ee drop to 60%. Again, it was shown that the reaction conld be performed on a preparative scale (1 mmol), and that the catalyst solution conld be recycled withont loss of activity or enanti-oselectivity over at least two rnns. 

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... 

The methylene deri ative of dimethylmalonic ester was prepai ed b> Meerwein and Schiiirnann b who reacted dimethyl malonate with commercial formaldehyde solution, using piperidine as a catalyst. According to these in estigatol s, it distills at 200-203 °C and polT-unerizes on standing to a nibber-like mass. 

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