Malonate ester anions

Less basic malonic ester anions may be employed for the twofold alkylation of dibro-... 

Some straightforward, efficient cyclopentanellation procedures were developed recently. Addition of a malonic ester anion to a cyclopropane-1,1-dicarboxylic ester followed by a Dieckmann condensation (S. Danishefsky, 1974) or addition of iJ-ketoester anions to a (l-phenylthiocyclopropyl)phosphonium cation followed by intramolecular Wittig reaction (J.P, Marino. 1975) produced cyclopentanones. Another procedure starts with a (2 + 21-cycloaddition of dichloroketene to alkenes followed by regioselective ring expansion with diazomethane. The resulting 2,2-dichlorocyclopentanones can be converted to a large variety of cyclopentane derivatives (A.E. Greene. 1979 J.-P. Deprds, 1980). 

A variety of cyclopropyl derivatives has been prepared utilizing this methodology from malonic ester anion or related stabilized carbanions and Michael acceptors such as 56,57310 and 58311. The reactions are nonstereospecific in general as expected from the mechanism... 

Less basic malonic ester anions may be employed for the twofold alkylation of dibromides. Cyclic 1,1-dicarboxylic esters are formed, if the reaction is executed in an appropriate manner. In the synthesis of cyclobutane diester A the undesired open-chain tetraester B was always a side product (J.A. Cason, 1949), the malonic ester and its monoalkylation product were always only partially ionized. Alkylation was therefore slow and intermolecular reactions of mono-alkyl intermediates with excess malonic ester prevailed. If the malonic ester was dissolved in ethanol containing sodium ethoxide, and 1,3-dibromopropane as well as more sodium ethoxide were added slowly to the solution, 63% of A and only 7% of B were isolated. The latter operations kept the malonic ester and its monoalkylated product in the ionic form, and the dibromide concentration low, so that the intramolecular reaction was favored against intermolecular reactions. The continuous addition of base during the reaction kept the ethoxide concentration low, which helped to prevent decomposition of the bromide by this nucleophile. 

The malonic ester anion performs a nucleophilic attack on the aldehyde citronellal (9). 

A palladium-cataly/ed C-C coupling reaction—the Heck reaction — is used in the construction of bicyclic system 13. Cyclization leads to a q3-alIyl-Pd complex, which undergoes nucleophilic attack by malonic ester anion 12. This in turn leads to formation of the C4 side chain The mechanism of this reaction therefore differs from that of a normal Heck reaction. 

The chiral monodeuterated ethanols 28 and 33 were obtained by Simon s method [33] and their tosylates, 29 and 34, reacted with malonic ester anion to afford 30 and 35. The expected inversion of configuration in the malonic ester synthesis was confirmed by decarboxylating the derived acids 31 and 36 to (35)- and (3R)-[3-2H,]butanoic acids, respectively, the chiroptical properties of which were already known [34]. The chirally deuterated CoA esters 32 and 37, prepared from 31 and 36, were rearranged on methylmalonyl-CoA mutase from P. shermanii and, after hydrolysis, the methylsuccinate products were isolated. In a parallel experiment the... 

When adding malonic ester anion to an allenic sulfoxide, rearrangement of the derived addition product leads to an allylic alcohol which cyclizes to (18) and isomerizes to the isolated product (19). If one alkylates the intermediate carbanion one gets an entry to a -methylenelactone system (18 Scheme 23). ... 

However, not only heterocyclic but also carbocyclic systems can be made via nucleophilic attack at propargylic centers. This is usually done intramolecularly as shown in Eq. (7), when a malonic ester anion displaces a propargylic chloride [16]. 

The same careful studies that led Begtrup and Pedersen to an understanding of alkylation in hydroxy-1,2,3-triazoles have produced important esterification methods. An especially interesting early examples involves the preparation of the internal salt 8.1>7 and its reaction with benzoyl chloride (Eq. 12). The direct reaction with benzoyl chloride often leads to both N-and O-benzoylation (Eq. 13), but the ester can be obtained in excellent yield by selective hydrolysis. A new method developed in this work starts from the malonic ester anion (Eq. 14) although the yields are not great, the method is potentially important. ... 

Anions of methylene-active compounds (1,3-dione enolates and ester enolates), ketene acetals, and even electron-rich five-membered heterocycles comprise another group of nucleophiles that attack triazine rings, preferably in the form of l,2,3-triazin-2-ium salts. 4,6-Disubstituted-2-methyl-l,2,3-triazinium iodides add malonic ester anion at the C-5 position to form 4,6-disubstituted-2-methyl-5-bis(ethoxy-carbonyl)methyl-2,5-dihydro-l,2,3-triazines in 57-76% yield <1992CPB2283, 1996CHEC-II(6)483>. The following cases have been published more recently. 

Table 3.11. Relative Rates of Cyclization of Diethyl (fti-Bromoalkyl)-malonate Ester Anions as a Function of Ring Size"...

Relative rates of cyclization of diethyl (o)-bromoalkyl)malonate ester anions as a function of ring size... 

However, if Y is the cyclopentadienyl ion or malonic ester anion, contraction of the ring takes place, leading to the formation of a neutral arene complex (11.18). 

Figure 1 - Addition of malonate ester anions to chalcone...

Linear Alkenes.—Addition of Nucleophiles. Nucleophilic attack on co-ordinated olefins generally occurs only with strong nucleophiles or if the complex is activated, e.g. if it is positively charged. However, malonate ester anions readily add to an olefinic carbon atom of [Fe(CO)4olefin] (olefin=ethylene or methylacrylate). Acidic work-up affords alkene addition products in good yield, equation (4), and a... 

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