Alkylation malonate anion

The malonic ester required for synthesis of cyclopal (107) can be obtained by alkylation of diethyl allylmalonate (115) with 1,2-dibromocyclopentane in the presence of excess base. It is probable that the reaction proceeds by elimination of hydrogen bromide from the dihalide as the first step. The resulting allilic halide (116) would be the most reactive electrophile in the reaction mixture and thus would quickly alkylate the anion of the malonate to afford 117. 

Alkylation of allylic acetates (formates or chlorides) with the dimethyl malonate anion is catalyzed by sodium tricarbonyl(nitroso)iron90. The nucleophile attacks the less hindered site... 

Stable enolates such as diethyl malonate anions react with allyl sulfones (or acetates) in the presence of nickel complexes to give a mixture of the a- and /-product83. The regioselectivity is generally poor in the nickel-catalyzed reaction, but the molybdenum-catalyzed reaction is selective for alkylation at the more substituted allylic site, thereby creating a quaternary carbon center84. 

Stereoselective allylic alkylations have been carried out with the aid of palladium catalysts. The 17-(Z)-ethylidene groups of steroids (obtained from the ketones by Wittig olefination) form n-allyl palladium complexes in the presence of copper(n) salts (B.M. Trost, 1974, 1976). Their alkylation with dimethyl malonate anions in the presence of 1,2-ethane-diylbis[diphenylphosphine] (— diphos) gives a reaction exclusively at the side chain and only the (20S) products. If one starts with the endocyclic 16,17 double bond and replaces an (S)-20-acetoxy group by using tetrakis(triphenylphospbine)palladium,the substitution occurs with complete retention of configuration, resulting from two complete inversions (B.M. Trost, 1976). 

Malonate anions react with the ri2-ethylene-Fe(CO)4 complex to afford after demetallation ethyl malonate derivatives. Reaction of nucleophiles with tetracar-bonyliron-activated c/.Jl-unsatu rated carbonyl compounds leads after protonation of the intermediate alkyl-Fe(CO)4 anions to the products of Michael addition. 

This method is useful for aryl-substituted malonates 27 where the normal alkylation of the malonate anion 26 is impossible as Sn2 reactions fail on unactivated aryl halides. For Ar = Ph reaction of 28 with NaH and diethyl carbonate gives3 27 Ar = Ph in 86% yield. 

A particularly clear example of syn versus anti addition was carried out in stoichiometric fashion using vinyl-zirconium reagents, in direct comparison with the stereochemical outcome of the catalytic ally lie alkylation with soft anions (Scheme 17). The zirconium reagent gives the natural steroid coiffiguration, while the malonate anion gives the opposite... 

Recently, a new ruthenium catalyst that also provides regioselective allylic alkylation has been reported. In DMF, a highly branched alkylation product of cinnamyl carbonate vsdth malonate anion was obtained in quantitative yield (branched/line-ar = 14/1) within 30 min in the presence of 1 mol% of [(C5Me5)Ru(MeCN)3]PF6 catalyst (Eq. 5.30) [46]. 

The trimethylsilyloxy group of allylic or benzylic alcohols is readily displaced by nucleophiles (malonate anion, alkyl Grignard reagents, hydride (AlCl3-LiAlHif)).91 This limitation as a protecting group should be noted. 

Addition of the malonate anion to an alkyl cycloprop-l-ene-l-carboxylate gave an EjZ mixture of cyclopropanes... 

Kim and Hollingsworth prepared a C-glycoside of A-acetylglucosamine by alkylation of a pyranosyl bromide with malonate anion, giving an A-acetyl y-sugar amino acid after decarboxylation (Fig. 13) [30]. 

The classical Strecker-type synthesis involving the addition of cyanide to aldehydes, ammonolysis of the cyanohydrin, and hydrolysis of the nitrile, yields racemates. More reactive than the cyanide anion are the azolactones for aromatic aldehydes or acetamido-malonate anions for Michael additions or alkylations (Scheme 9.3.1). 

Alkylation of malonate anion Hernandez et al. [155, 156] have developed a rapid and easy procedure for the synthesis of C-labeled esters using a combination of solvent-free phase-transfer catalysis conditions and microwave technology. A detailed study of the first step, which consists in malonic alkylation, did not reveal any advantages of microwave activation compared with conventional heating (Eq. 71) ... 

The stereoselectivity displayed during the alkylation of 43 (Scheme 25) was quite surprising, considering that formation of the major diastereomer (endo-44) requires the electrophile to approach bicyclic malonate anion 69 firom what appears to be the more crowded endo (concave) face. This is cotmter to what is commonly perceived as a reliable strategy for stereoinduc-tion. At the time, we had tried several experiments attempting to alter the diastereoselectivity, but to no avail. In the end, we reluctantly accepted the... 

Allylation of Stabilized Anions. Electrophilic 7r-allyl Pd(0) complexes can be generated from Pd(dba)2 and functionalized allylic acetates, carbonates, halides, etc. These complexes are susceptible to reaction with a range of stabilized nucleophiles, such as malonate anions. Alkylation usually occurs at the less-substituted allylic terminus. Silyl-substituted r-allyl complexes undergo re-gioselective alkylation at the allyl terminus farthest removed from the silyl group (eq 14). ... 

Microwaves Alkylation of ethylphenyl sulfonyl acetate, diethyl malonate, anions derived from active methylene Dihalocyclopropanation of substituted olefins under LLPTC and SLPTC conditions Ethoxylation of o,p-nitrochlorobenzene Reactions of carboxylic acids with halides Wang and Jiang (1992), Wang et al. (1995) Villemin and Labiad (1992) Yuan et al. (1992a) Yuan et al. (1992b)... 

A wide range of transition metal-allyl complexes are known to react with many types of nucleophiles. In most cases, these reactions occur between cationic allyl complexes and amines or stabilized, anionic carbon nucleophiles. The reaction typically occurs between the nucleophile and the form of the allyl complex, and attack usually occurs at the face of the allyl ligand opposite the metal. However, there are exceptions to these trends. For example, several experiments suggest that unstabilized carbon nucleophiles react first at the metal center, and C-C bond formation occurs between the alkyl and the allyl group by reductive elimination. In addition, a recent study has shown through deuterium labeling that attack of malonate anion on a molybdenum-allyl complex occurs with retention of configuration. ... 

Dearomatization of r -benzylpalladium complexes represents an electronically reversed variation on the reactions described earlier. Initial examples utilized allyl and allenyl stan-nanes as nucleophilic components in combination with benzyl halides and invoked mechanisms involving aryl-alkyl Pd(II) intermediates [84]. Subsequently, direct addition of stabilized nucleophiles (e.g., malonate anions) to q -naphthylpalladium complexes has been achieved [85]. 

Malonate anions react at low temperatures (0—25 C) with cyclic a-haloketones via a Favorskii-type mechanism leading to jS-keto-esters (153) in reasonable yields (Scheme 17). " Reactions at higher temperatures result in simple 5n2 substitution. Specific Dieckmann cyclizations of alkyl pimelates can be effected by attaching one end of the substrate to a polymer support. ... 

The second method involves end-quenching of living polymers with appropriate nucleophiles. Although this approach appears to be more attractive than the first one, in situ end funaionali-zation of the living ends is limited to nucleophiles that do not react with the Lewis add coinitiator. Because the ionization equilibrium is shifted to the covalent spedes, the concentration of the ionic active species is very low. Quantitative functionalization can only be accomplished when ionization takes place continuously in the presence of nudeophile. Quenching the vinyl ether polymerization with the malonate anion,certain silyl enol ethers " and silyl ketene acetals have been successfully used to synthesize end-functionalized poly(vinyl ethers). Alkyl amines, " ring-substituted anilines, " " alcohols, " and water " have also been used to quench the vinyl... 

The first example of an allylic alkylation catalyzed by iron compounds was reported in 1979. Allylic halides and carboxylates are treated with a diethyl malonate anion in the presence of sodium tricarbonyl(nitrosyl)ferrate to give the allylated malonates with good regioselectivity in favor of the ipso product (Scheme 4-195). This transformation can be carried out in a carbon monoxide atmosphere catalyzed by the Hieber-type complex [Bu4N][Fe(CO)3NO] (TBAFe) that is easier to handle. The... 

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) ... 

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 ... 

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

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