Malonic ester enolates

The use of /i-ketocstcrs and malonic ester enolates has largely been supplanted by the development of the newer procedures based on selective enolate formation that permit direct alkylation of ketone and ester enolates and avoid the hydrolysis and decarboxylation of ketoesters intermediates. Most enolate alkylations are carried out by deprotonating the ketone under conditions that are appropriate for kinetic or thermodynamic control. Enolates can also be prepared from silyl enol ethers and by reduction of enones (see Section 1.3). Alkylation also can be carried out using silyl enol ethers by reaction with fluoride ion.31 Tetraalkylammonium fluoride salts in anhydrous solvents are normally the... 

Fig. 12.9. Nitrosation of malonic acid diethyl ester. The mechanism of the acid-catalyzed enolization malonic ester malonic ester enol (E) and the mechanism of the actual nitrozation (E -> A) is shown here.

Fig. 12.11. Mechanism of the tert-butylation of malonic acid diethyl ester. From the point of view of tert-butyl chloride it is an SN1 reaction with the malonic ester enol (B) acting as the nucleophile.

Michael additions are useful in acetoacetic ester syntheses and malonic ester syntheses because the enolate ions of both of these esters are good Michael donors. As an example, let s consider the addition of the malonic ester enolate to methyl vinyl ketone (MVK). The crucial step is the nucleophilic attack by the enolate at the carbon. The resulting enolate is strongly basic, and it is quickly protonated. 

Activation of allylic ethers. An allylic ether y to an electron-withdrawing group is activated by forming the Fe(CO)4 complex. On acid treatment ionization occurs to generate the allyl cation (still complexed to iron), which is reactive towards nucleophiles such as silyl enol ethers, malonate ester enolates, etc. The substitution is stereoselective. ... 

Electrophilic activation of allylic alcohols. Formation of lithium allyloxy-triphenylborates enables the Pd(0)-catalyzed substitution of allyl alcohols with soft nucleophiles such as malonate ester enolates. 

Diesters.—Michael addition of malonic ester enolates to chiral a/3-unsaturated aldimines (obtained from optically pure a-amino-acids) gives, after hydrolysis, aldehyde-diesters (125) in variable chemical (26—54%) and optical (36—86%) yields. The amino-acid components are recovered optically pure. Attack of simple nucleophiles on the bromoalkylidene malonate (126) gives cyclopropane diesters (127) in good yields. A ready, five-step route to the bicyclo[l,l,0]butane triester (128) has been described. ... 

Scheme 1.2 8 2 reaction with malonic ester enolates. 

As an example, ferf-butyl (45)-l-methyl-2-oxoimidazolidine-4-carboxylate was used by Nunami and colleagues as a chiral auxiliary for DKR of a-bromo-carboxylic acids. In this case, the nucleophile was a malonic ester enolate and the role of the polarity of the solvent (hexamethylphosphoramide, HMPA) was demonstrated (Scheme 1.2). The alkylated products were further easily converted to chiral a-alkylsuccinic acid derivatives and chiral jS-amino acid derivatives. Moreover, these authors showed that this methodology could be extended to other nucleophiles such as amines." Therefore, the reaction of a diastereomeric mixture of tert-bvAy (45)-l-methyl-2-oxoimidazolidine-4-carb-oxylate with potassium phthalimide predominantly afforded fcrf-butyl (45)-1-methyl-3-((25)-2-(phthaloylamino)propionyl)-2-oxoimidazolidine-4-carboxylate in 90% yield and 94% diastereomeric excess (de). The successive removal of the chiral auxiliary afforded A-phthaloyl-L-alanine. 

Pyrrolidone anion as EGB generates (trifluoromethyl) malonic ester enolate from malonic ester bearing a CF3 moiety at the a-position (Eq. 26). Generally, it is difficult to generate the enolate anion with a-CFg group, because the enolate anion undergoes... 

FuchigamiT NY (1987) Electrolytic transformation of fluoroorganic compounds. 2. Generation and alkylation of a stable (trifluoromethyl)malonic ester enolate using an electrogenerated base. J Org Chem 52 5276-5277... 

In case of functionalization by soft nucleophiles, poly(ferrocenyl(3-iodo-propyl)methylsilane) 3b is a suitable starting material. Malonic ester enolates such as dimethyl methylmalonate anion or dibenzyl methylmalonate anion smoothly react to produce the corresponding polyesters with quantitative conversions. By using hydrolytically labile ester enolates, such as methyl trimethylsilyl methylmalonate anion, one can easily convert the corresponding pendent ester groups into car-boxylate salts, thus forming an organometallic polyanion (see Scheme 3). 

The use of j8-ketoesters and malonate ester enolates has, to a significant extent, been supplanted by the development of procedures which are satisfactory for direct... 

Hydroxymethylation is achieved by crossed aldol addition reaction (Section 18-6) of the malonic ester enolate with formaldehyde. 

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