Carbanions malonate

In DMF, with carbanions (malonates or nitronates) as nucleophiles and phenylthio or phenylsulphonyl leaving groups, a chain radical substitution takes place at an allylic carbon. This SRN1 like reaction was found to be activated by visible light, the only possible absorbing species being a charge transfer complex between the anion and the substrate [218]. 

The role of the base is apparently primarily that of a proton remover from the reactive methylene group thus if B represents the base, reaction (i) gives the carbanion, which then combines with the positive carbon of the carbonyl group (reaction ii) the product regains a proton from the piperidinium ion, and then by loss of water followed by mono-decarboxylation of the malonic acid residue gives the final acid. 

The sodiocompound may be written [CHtCOOCjHjij] Na, and it must always be home in mind that the anion is mesomeric. The system reacts smoothly with an alkyl halide to give a C-substituted malonic ester, evidently through the carbanion (I) ... 

A classical way to achieve regioselectivity in an (a -i- d -reaction is to start with a-carbanions of carboxylic acid derivatives and electrophilic ketones. Most successful are condensations with 1,3-dicarbonyl carbanions, e.g. with malonic acid derivatives, since they can be produced at low pH, where ketones do not enolize. Succinic acid derivatives can also be de-protonated and added to ketones (Stobbe condensation). In the first example given below a Dieckmann condensation on a nitrile follows a Stobbe condensation, and selectivity is dictated by the tricyclic educt neither the nitrile group nor the ketone is enolizable (W.S. Johnson, 1945, 1947). 

Facile reaction of a carbon nucleophile with an olefinic bond of COD is the first example of carbon-carbon bond formation by means of Pd. COD forms a stable complex with PdCl2. When this complex 192 is treated with malonate or acetoacetate in ether under heterogeneous conditions at room temperature in the presence of Na2C03, a facile carbopalladation takes place to give the new complex 193, formed by the introduction of malonate to COD. The complex has TT-olefin and cr-Pd bonds. By the treatment of the new complex 193 with a base, the malonate carbanion attacks the cr-Pd—C bond, affording the bicy-clo[6.1,0]-nonane 194. The complex also reacts with another molecule of malonate which attacks the rr-olefin bond to give the bicyclo[3.3.0]octane 195 by a transannulation reaction[l2.191]. The formation of 194 involves the novel cyclopropanation reaction of alkenes by nucleophilic attack of two carbanions. 

Substances that form carbanions, such as nitro compounds, hydrocyanic acid, malonic acid, or acetylacetone, react with vinyl ethers in the presence of water, replacing the alkyl group under mild conditions (245). 

With active methylene compounds, the carbanion substitutes for the hydroxyl group of aHyl alcohol (17,20). Reaction of aHyl alcohol with acetylacetone at 85°C for 3 h yields 70% monoaHyl compound and 26% diaHyl compound. Malonic acid ester in which the hydrogen atom of its active methylene is substituted by A/-acetyl, undergoes the same substitution reaction with aHyl alcohol and subsequendy yields a-amino acid by decarboxylation (21). 

Carbon is alkylated ia the form of enolates or as carbanions. The enolates are ambident ia activity and can react at an oxygen or a carbon. For example, refluxing equimolar amounts of dimethyl sulfate and ethyl acetoacetate with potassium carbonate gives a 36% yield of the 0-methylation product, ie, ethyl 3-methoxy-2-butenoate, and 30% of the C-methylation product, ie, ethyl 2-methyl-3-oxobutanoate (26). Generally, only one alkyl group of the sulfate reacts with beta-diketones, beta-ketoesters, or malonates (27). Factors affecting the 0 C alkylation ratio have been extensively studied (28). Reaction ia the presence of soHd Al O results mosdy ia C-alkylation of ethyl acetoacetate (29). 

The most useful reactions combine carbanion nucleophiles with activated aziridines. For example, the ring expansion which occurs on treatment of aziridines (219) with malonate salts typifies the heterocyclic synthesis possible. The conversion is quite general since many analogous transformations have been observed in which different carbanion stabilizing substituents were employed (73S546). 

Carbanions of active methylene compounds also react with aziridine-2-car-boxylic esters to give ring-opened products [129]. The ring-opened intermediates usually cyclize spontaneously to pyrrolidones. Treatment of 190 (Scheme 3.70) with the sodium enolate of dimethyl malonate 191, for example, afforded pyrroli-done 192 in 15% isolated yield, together with 30% of the debenzoylated product 193. 

The cyclization involves a nucleophilic attack of the malonic ester car-banion on the carbonyl carbon atom of the aldehyde, and the substituted malonic ester carbanion attacks the electron-deficient carbon atom bearing the iodine atom, or in the reverse order, to give 119. The hydroxyl group generated in the first step of the reaction attacks the carbon atom, giving the pyranose product. 

In this chapter, decarboxylation of disubstituted malonic acid derivatives and application of the transketolases in organic syntheses are summarized. Although decarboxylation may be seen as a simple C-C bond breaking reaction, it can be regarded as a carbaniongenerating reaction. As the future directions of this field, expansion of some unique decarboxylation reactions is proposed. In relation of carbanion chemistry, promiscuity of enolase superfamily is discussed. 

Although the reaction mechanism of this type of reactions is not fully elucidated, it is easily anticipated that no intramolecular special stabilization effect for the carbanion generated from decarboxylation is expected, different from the case of malonic acid-type compounds. Moreover, cinnamic acid derivatives that have both the electron-donating and withdrawing substituents have been reported to undergo this reaction. This fact suggests that the enzyme itself stabilizes the transition state without the aid of mesomeric and inductive effects of the other part of the substrate molecule itself. If such unknown mechanism also works for other... 

The decarboxylation reaction usually proceeds from the dissociated form of a carboxyl group. As a result, the primary reaction intermediate is more or less a carbanion-like species. In one case, the carbanion is stabilized by the adjacent carbonyl group to form an enolate intermediate as seen in the case of decarboxylation of malonic acid and tropic acid derivatives. In the other case, the anion is stabilized by the aid of the thiazolium ring of TPP. This is the case of transketolases. The formation of carbanion equivalents is essentially important in the synthetic chemistry no matter what methods one takes, i.e., enzymatic or ordinary chemical. They undergo C—C bond-forming reactions with carbonyl compounds as well as a number of reactions with electrophiles, such as protonation, Michael-type addition, substitution with pyrophosphate and halides and so on. In this context,... 

Examples of this approach to the synthesis of ketones and carboxylic acids are presented in Scheme 1.4. In these procedures, an ester group is removed by hydrolysis and decarboxylation after the alkylation step. The malonate and acetoacetate carbanions are the synthetic equivalents of the simpler carbanions that lack the additional ester substituent. 

Nucleophilic Substitution of xi-Allyl Palladium Complexes. TT-Allyl palladium species are subject to a number of useful reactions that result in allylation of nucleophiles.114 The reaction can be applied to carbon-carbon bond formation using relatively stable carbanions, such as those derived from malonate esters and (3-sulfonyl esters.115 The TT-allyl complexes are usually generated in situ by reaction of an allylic acetate with a catalytic amount of fefrafcz s-(triphenylphosphine)palladium... 

The Balme group [82] also used the anion capture approach to develop a short entry to triquinanes as 6/1-150 forming a transient Pdn-complex in a Heck reaction of the vinyl iodide 6/1-149 (Scheme 6/1.39). The latter reacts with the carbanion ofa malonate moiety in the substrate however, the products of the normal Heck reaction are also formed. 

There are very few precedents for the reaction of cyclic a-halo ethers with carbanions. Zelinski and coworkers114 and Schudel and Rice115 reported the preparation of diethyl DL-tetrahydropyran-2-ylmalonate (137) by treatment of 2-bromo- or 2-chloro-tetrahydropyran (136) with diethyl sodiomalonate. The product was subsequently converted into the malonic and acetic acid derivatives, 138 and 139, respectively. The same sequence has also been reported by other workers.116... 

Boron trichloride appears to form with methyl /3-D-ribofuranoside a complex which, after treatment with appropriate nucleophiles, such as sodium methoxide, or the carbanion derived from diethyl 2-(ethox-ycarbonylmethyl)malonate, gives the corresponding a-glycosyl compound.147... 

This reaction was easily performed with malonic ester derivatives using approaches described above for nitro carbanions. It should be noted that the anion of malonic ester can be prepared not only by the reactions of bases with malonates but also by desilylation of silyl ketene acetal (449) with fluoride anion. 

The carbanions are involved in a number of substitutaion reactions. The example are the formation of mono and dialkyl malonic esters. 

Oxazinone (411) was reacted with the carbanion of diethyl malonate to give (substituted amino)phenylmethylenemalonate (412) (86MI1). 

Di(methyIthio)-l,2,5-thiadiazole 1-oxide reacted readily with the carbanion of diethyl malonate to yield (1,2,5-thiadiazol-3-ylidene)malonate (482) in high yield [81H( 16)1561]. 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

The carbanion derived from dimethyl malonate reacts with the cyclic nitro compounds 422 of ring size 5, 6, 7, 8 and 12 to afford the corresponding esters 423. Acyclic allylic nitro compounds 424 (R = Me, CH2OAC or CC Et) are attacked by bulky nucleophiles, such as dimethyl malonate anion, mainly at the terminal primary carbon atom to give rearranged products 425, whereas smaller nucleophiles, e.g. the anion derived from methyl cyanoacetate, react at the tertiary carbon atom to yield 426409a 453 455. 

Thus, PVC was substituted with xanthate (EtO-CSS ), dithiophosphate ((EtO)2P(=S)S ), thiourea, thiosulphate ( S-SO,),and even with carbanion such as dimethyl malonate/DBU to some extents. In the last case, PVC was reacted in tetrahydrofuran (THF) with a small excess of dimethylrnalonate in the presence of equimolar amounts of l,5-diazabicyclo[5,4,0]undec-5-ene (DBU). 

Diethyl malonate reacts with iodine under basic soliddiquid conditions (procedure 6.4.20 omitting the alkene) to produce tetraethyl ethane-1,1,2,2-tetracarboxylate (Scheme 6.28) [110] the ethenetetracarboxylate is also formed, presumably from the reaction of the initially formed iodomalonate with its carbanion and subsequent elimination of hydrogen iodide. 

Like the electrohydrodimerization and electrohydrocyclizahon reactions, this process also requires the consumphon of two electrons and two protons. It has been shown to occur via a sequence consisting of electron transfer followed by a ratedetermining protonation of the resulting radical anion, addihon of a second electron to generate a carbanion, cyclization of the carbanion onto the carbonyl acceptor unit and the addition of the second proton [16]. Carbon acids like dimethyl malonate and malononitrile are often used as a proton source. The course of this and other... 

Sulfonyl azides are exceptional in that they do not normally give triazoles with activated methylene compounds nucleophilic attack by the carbanion is usually followed by loss of the sulfonamide anion, giving a diazo compound as the product. Possible mechanisms for the reaction are illustrated (Scheme 8) for diethyl malonate. Attack of the carbanion on the terminus of the azide gives the anion of the linear triazene (1). 

Acetone cyanohydrin nitrate, a reagent prepared from the nitration of acetone cyanohydrin with acetic anhydride-nitric acid, has been used for the alkaline nitration of alkyl-substituted malonate esters. In these reactions sodium hydride is used to form the carbanions of the malonate esters, which on reaction with acetone cyanohydrin nitrate form the corresponding nitromalonates. The use of a 100 % excess of sodium hydride in these reactions causes the nitromalonates to decompose by decarboxylation to the corresponding a-nitroesters. Alkyl-substituted acetoacetic acid esters behave in a similar way and have been used to synthesize a-nitroesters. Yields of a-nitroesters from both methods average 50-55 %. 

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