From active methylene compounds

Wylation under neutral conditions. Reactions which proceed under neutral conditions are highly desirable, Allylation with allylic acetates and phosphates is carried out under basic conditions. Almost no reaction of these allylic Compounds takes place in the absence of bases. The useful allylation under neutral conditions is possible with some allylic compounds. Among them, allylic carbonates 218 are the most reactive and their reactions proceed under neutral conditions[13,14,134], In the mechanism shown, the oxidative addition of the allyl carbonates 218 is followed by decarboxylation as an irreversible process to afford the 7r-allylpalladium alkoxide 219. and the generated alkoxide is sufficiently basic to pick up a proton from active methylene compounds, yielding 220. This in situ formation of the alkoxide. which is a... 

Aldol Addition and Related Reactions. Procedures that involve the formation and subsequent reaction of anions derived from active methylene compounds constitute a very important and synthetically useful class of organic reactions. Perhaps the most common are those reactions in which the anion, usually called an enolate, is formed by removal of a proton from the carbon atom alpha to the carbonyl group. Addition of this enolate to another carbonyl of an aldehyde or ketone, followed by protonation, constitutes aldol addition, for example... 

Other Applications. Hydroxylamine-O-sulfonic acid [2950-43-8] h.2is many applications in the area of organic synthesis. The use of this material for organic transformations has been thoroughly reviewed (125,126). The preparation of the acid involves the reaction of hydroxjlamine [5470-11-1] with oleum in the presence of ammonium sulfate [7783-20-2] (127). The acid has found appHcation in the preparation of hydra2ines from amines, aUphatic amines from activated methylene compounds, aromatic amines from activated aromatic compounds, amides from esters, and oximes. It is also an important reagent in reductive deamination and specialty nitrile production. 

The reaction of A-acyliminium ions with nucleophilic carbon atoms (also called cationic x-amidoalkylation) is a highly useful method for the synthesis of both nitrogen heterocycles and open-chain nitrogen compounds. A variety of carbon nucleophiles can be used, such as aromatic compounds, alkcncs, alkyncs, carbcnoids, and carbanions derived from active methylene compounds and organometallics. 

Addition of carbanions (which may be electrochemically generated), derived from active methylene compounds (such as fluorene or indene193), to nitrosobenzene produces the intermediate181 70, which is dehydrated to the azomethine 71 or may be oxidized to the nitrone derivative 72, as illustrated by Scheme 8. 

Examples of the Michael-type addition of carbanions, derived from activated methylene compounds, with electron-deficient alkenes under phase-transfer catalytic conditions have been reported [e.g. 1-17] (Table 6.16). Although the basic conditions are normally provided by sodium hydroxide or potassium carbonate, fluoride and cyanide salts have also been used [e.g. 1, 12-14]. Soliddiquid two-phase systems, with or without added organic solvent [e.g. 15-18] and polymer-supported catalysts [11] have been employed, as well as normal liquiddiquid conditions. The micellar ammonium catalysts have also been used, e.g. for the condensation of p-dicarbonyl compounds with but-3-en-2-one [19], and they are reported to be superior to tetra-n-butylammonium bromide at low base concentrations. 

Decarboxylation of 1,3-dimethylorotic acid in the presence of benzyl bromide yields 6-benzyl-1,3-dimethyluracil and presumably involves a C(6) centered nucleophilic intermediate which could nonetheless have either a carbene or ylide structure. Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry has been used to explore the gas-phase reactions of methyl nitrate with anions from active methylene compounds anions of aliphatic ketones and nitriles react by the 5n2 mechanism and Fco reactions yielding N02 ions are also observed nitronate ions are formed on reaction with the carbanions derived from toluenes and methylpyridines. 

Other Applications. Hydroxylainine-O-sulfonic acid has many applications in the area of organic synthesis. The acid has found application in the preparation of hydrazines from amines, aliphatic amines from activated methylene compounds, aromatic amines from activated aromatic compounds, amides from esters, and oximes. 

Aromatization of Triazolines Derived from Active Methylene Compounds... 

The interesting zwitterionic compound (39) with the cationic component a butadien-2-yl cation was obtained by reaction of l,4-di(t-butyl)butadiyne with 2 mol of di(r-butyl)aluminium hydride, with the structure being established by X-ray analysis.80 The reactions of the l,2-diferrocenyl-3-(methylthio)cyclopropenylium ion with carbanions derived from active methylene compounds were investigated.81 Products were derived by ring opening of the cyclopropene ring after the initial carbanion addition. The bis(ferrocenylethynyl)phenylmethylium cation (Fc-C=C-)2C+Ph (Fc = ferrocenyl) was prepared 82 This cation proved to be much less stable than its bis-ethenyl analogue (Fc-CH=CH-)2C+Ph. 

Type III reactions proceed by attack of a nucleophile at the central sp carbon of the allenyl system of the complexes 5. Reactions of soft carbon nucleophiles derived from active methylene compounds, such as /i-kcto esters or malonates, and oxygen nucleophiles belong to this type. The attack of the nucleophile generates the intermediates 9, which are regarded as the palladium-carbene complexes 10. The intermediates 9 pick up a proton from the active methylene compound and n-allylpalladium complexes 11 are formed, which undergo further reaction with the nucleophile, as expected, and hence the alkenes 12 are formed by the introduction of two nucleophiles. 

According to Figure 13.1, carbon-bound H atoms are acidic if they are bound to carbon atoms that are in the a-position with respect to an electron acceptor that can stabilize a negative charge via resonance (-M effect). Carbon-bound H atoms are even more acidic if they are located in the opposition of two such electron acceptors, which is the case in the so-called active-methylene compounds. Enolates derived from active-methylene compounds require three resonance forms for their description, and resonance forms A and B (Figure 13.6) are the more important ones. Compounds that contain an FI atom in the Opposition with respect to three electron acceptors are even more acidic than active-methylene compounds. However, such compounds do not play a significant role in organic chemistry. 

MCI reactions of alkynyliodonium salts with enolates derived from active methylene compounds containing two acidic CH bonds follow a divergent course that leads to furans, presumably via carbenic insertion into enolic OH bonds (equation 122)28. In the reaction of acetylacetonate ion with the l-decynyl(phenyl)iodonium ion, CH insertion is competitive with OH insertion (equation 123)28. 

The cation radical intermediates formed from the enamines may be trapped by nucleophiles other than the solvent when these nucleophiles are electrochemically less oxidizable than the enamines. Indeed, the cation radical intermediates formed from morpholino-, piperidino-and pyrrolidinoenamines are trapped by carbanions derived from active methylene compounds such as methyl acetoacetate, acetylacetone and dimethyl malonate with moderate yields (equation 2)3. The products are easily transformed to the corresponding a-substituted ketones by hydrolysis with dilute hydrochloric acid. 

Nitriles have also been obtained recently from active methylene compounds of type 1 by a two-step process. Treatment with the aminal ester 2 (5, 71-73) leads to an enamine (3), which reacts with hydroxylamine-O-sulfonic acid in an aqueous medium to give a nitrile (4). This reaction docs not proceed through an aldehyde,... 

Halogens (mainly chlorine) at position 4 of quinazolines 12 can be displaced by a variety of carbon nucleophiles, c.g. carbon nucleophiles derived from active methylene compounds, ketone enolates, aromatic aldehydes, organolithium reagents, alkylidenephosphorane, dimethyloxosulfonium methylide, alkynes, and cyanide. ... 

Chloroquinoxaline (1) reacts with anions derived from active methylene compounds thus, 2-chloroquinoxaline (1) has been condensed with six different substituted acetonitriles, an example of which is shown. 

Carbanions formed from active methylene compounds usually attack methylphenazinium salts at position C3. When this position is substituted, the nucleophilic attack is directed to position C7 in the unsubstituted benzenoid ring. " ... 

Nucleophilic substitution and addition reactions of olefins are possible with Pd2 salts. A typical example is the formation of acetaldehyde by the reaction of ethylene with water (Wacker reaction). As nucleophiles, water, alcohols, phenols, carboxylic acids, amines, enamines, carbanions derived from active methylene compounds, and carbon monoxide react with olefins with stoichiometric consumption of Pd2 salts. 

Excess diazomethane has been used to convert phenols to methyl ethers in the presence or absence of acids . Employment of transition metal derivatives, typically Rh2(OAc)4 and recently CHsReOs , allows one to react functionalized diazo compounds in an intramolecular or intermolecular 0-aUtylation (equation 13). The stability of diazo compounds derived from active methylene compounds toward OH insertion was compared... 

Obtained from active methylene compounds, such as malonic esters, -0x0 esters and jS-oxo sulfones, iodonium ylides serve as precursors of the corresponding carbenes. Their decomposition by a catalytic amount of a copper salt in the presence of a C-C double bond has been used for inter- and intramolecular cyclopropanation reactions. Thus, reaction of cyclohexene with bis(methoxycarbonyl)methylene(phenyl)iodine(III) under the catalytic action of bis(acetylacetonato)copper(II) yielded dimethyl bicyclo[4.1.0]heptane-7,7-dicarboxylate (1) (38%, mp 91-93°C) in addition to tetrakis(methoxycarbonyl)ethene (41%). ... 

The cisjtrans ratio of the cyclopropanes formed in this transformation depends to some extent on the nature of the salts and the solvent. A particularly high cisitram ratio was obtained when copper(II) acetate, calcium chloride, and ethanol were employed (no values given). Cyclopropane synthesis from active methylene compounds and nonactivated alkenes was also possible with the help of iodine and a base under phase-transfer conditions. Intra-and intermolecular reactions to give 6 and 5, respectively, have been carried out. The intramolecular reaction is nonstereospecific with respect to the C-C double bond. Although an iodo-substituted intermediate has been isolated in one case, all the details of the reaction mechanism are not yet clear. 

In a related transformation, cyclopropanes 7 were obtained from active methylene compounds and electron-deficient alkenes by the action of iodine and potassium fluoride supported on solid alumina. 

Comins, D.L., Jacobine, A.E. Marshall, J.A., and Turnbull, M.M., Phosphonate ester preparation from active methylene compounds and phosphorochloridate esters, Synthesix, 309, 1978. 

Khoukhi, M., Vaultier, M., and Carrie, R., The use of m-iodo azides as primary protected electrophihc reagents. Alkylation of some carbanions derived from active methylene compounds and V,V-dimclh-ylhydrazones. Tetrahedron Lett., 27, 1031, 1986. 

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