Ethyl acetoacetate dianion

Where will alkylation tend to occur on the ethyl acetoacetate dianion 73 Answer... 

In the presence of LiC104 the alkylation of the ethyl acetoacetate dianion with epibro-mohydrin leads to 2-ethoxycarbonylmethylene-5-hydroxymethyltetrahydrofuran. ... 

Treatment of 1,3-dicarbonyl eompounds with two equivalents of strong base ean give a dianion that will react selectively with alkyl halides. For example, ethyl acetoacetate reacts first with NaH to form an enolate, and then with n-BuLi to form a dianion. This then adds t-PrI. 

Next, examine the dianion resulting from double deprotonation of ethyl acetoacetate. Draw all the resonance contributors needed to describe this ion. Next, examine the geometry, atomic charges and electrostatic potential map for dianion. Are you able to decide which resonance contributors are important and which are not ... 

Monoanions derived from nitroalkanes are more prone to alkylate on oxygen rather than on carbon in reactions with alkyl halides, as discussed in Section 5.1. Methods to circumvent O-alkylation of nitro compounds are presented in Sections 5.1 and 5.4, in which alkylation of the a.a-dianions of primary nitro compounds and radial reactions are described. Palladium-catalyzed alkylation of nitro compounds offers another useful method for C-alkylation of nitro compounds. Tsuj i and Trost have developed the carbon-carbon bond forming reactions using 7t-allyl Pd complexes. Various nucleophiles such as the anions derived from diethyl malonate or ethyl acetoacetate are employed for this transformation, as shown in Scheme 5.7. This process is now one of the most important tools for synthesis of complex compounds.6811-1 Nitro compounds can participate in palladium-catalyzed alkylation, both as alkylating agents (see Section 7.1.2) and nucleophiles. This section summarizes the C-alkylation of nitro compounds using transition metals. 

As a result of the easy accessibility of fi-hydroxy carboxylates, even in their nonraccmic form, and also the predictable and high level of diastereoselectivity in the alkylation of their corresponding dianions, this methodology has become a broadly used synthetic tool (see Tables 1-3). (3S>11, the yeast reduction product of ethyl acetoacetate, is methylated in 68% yield with a d.r. of 95.5 4.5 via the lithium dianion with iodomethane16. 

Acylation of the dianion of ethyl acetoacetate by an ester is a useful addition to this area of pyranone synthesis. In this reaction and in the formation of the trianions of 2,4,6-triketones the use of lithium diisopropylamide as the base is valuable (76JA7733). The triketo acid from the trianion cyclizes in mineral acids to the pyran-4-one, but in acetic anhydride the pyran-2-one is formed (Scheme 101) (71JA2506). 

A more direct preparation4 of (5) is that of the alkylation of the dianion of ethyl acetoacetate with the bromide (12). 

Looking back on the history of ketone dianion chemistry, one soon notices that dianion species, derived from / -keto esters, have been in continuous steady use in organic synthesis3,4, as shown in Scheme 2. Thus, ethyl acetoacetate can be converted to the corresponding ketone o a -chainon via consecutive proton abstraction reactions. The resulting dienolate anion reacts with a variety of alkyl halides to give products, resulting from exclusive attack at the terminal enolate anions. 

The scope of the strategy was then extended in spectacular fashion (Scheme 6). The mixture of 19 and 20 was transformed into the corresponding aldehydes 26 through reduction/oxidation of the ester groups. Treatment with the dianion derived from ethyl acetoacetate then led to hydroxyketones 27. Chelation-controlled, syn-selective reduction [9] of this mixture followed by menthonide formation gave 28 as four diaste-... 

Some recent patents by Konishiroku refer to metallizable dyes of the dianionic type, with carboxyl groups as one of the hgands. A yellow pyridone (56) and a magenta naphthol dye (57) are two examples. Patents assigned to Agfa-Gevaert describe cyan metallizable dyes from imidazo[I,5-a]pyridine such as (58) and yellow dyes " from ethyl acetoacetate such as (59). A Fuji patent discloses a dye-releasing compound in which the dye is initially complexed with a metal... 

A synthetic strategy was developed for the typical core structure of the Stemona alkaloids in the laboratory of C.H. Heathcock. " The precursor for the 1-azabicyclo[5.3.0]decane ring system was prepared via the successive double alkylation of the dianion of ethyl acetoacetate. 

Osowska-Pacewicka, K., Zwierzak, A. Reactions of N-phosphorylated aziridines with dianions derived from ethyl acetoacetate and 1,3-diketones new route to substituted pyrrolines and pyrrolidines. Synth. Commun. 1998, 28,1127-1137. 

Ethyl 5-oxohexanoate (51) was reduced with NaBH4 and the resulting alcohol protected with dihydropyran to give 52. Reduction of the ester moiety to a primary alcohol followed by conversion to the bromide 53 was achieved by conventional means. Alkylation of the dianion of ethyl acetoacetate with 53 afforded a 78% yield the p-keto ester 54, which possesses all the carbons required for the construction of the diplodialides. Protection of the ketone as the dithiane... 

A tandem anionic cyclization/Dimroth rearrangement was employed for the preparation of y-lactams containing alkylidene substituents (02EJOC221). In this cascade sequence, the dianion of ethyl acetoacetate (272) reacted with 273 to provide furan derivative 274 (Scheme 50) which underwent a subsequent rearrangement to give 275 in 56% yield (04EJOC1897). 

Intermolecular reactions involving non-aromatic precursors have been used to furnish salicylate esters., p-Unsaturated aldehydes have been reacted with the dianion (DA) of ethyl acetoacetate to afford 4-substituted salicylates in good yield (ref. 36). 6-Methylsalicylates result from the addition of the monoanion (MA) at C2 (ref.37). 

Secocitreoviridin (47), a metabolite of Penicillium citreo-viride, has been synthesized from 5,6-dimethyl-4-hydroxypyran-2-one.57 Another fungal metabolite, phacidin (48 R=CHO), has been prepared from triacetic acid lactone. Related compounds (48 R=H or R=Br) have been obtained by condensation of the dianion of ethyl acetoacetate with a substituted 1,3-dithian-2-carboxaldehyde.58... 

The dianion from ethyl acetoacetate was carried through the reaction sequence shown. What was the product (compound X) ... 

Scheme 5.6 Ethyl acetoacetate as synthetic equivalent for the acetonyl-l,l-dianion...

Ring expansion of epoxides by the addition of the dianion of ethyl acetoacetate under Lewis acid conditions followed by cycli-... 

If ethyl acetoacetate is treated with two equivalents of LDA, a dianion is formed. This dienolate is more reactive at the end carbon, since that anion is delocalized over just one EWG the other anion is alpha to two EWGs, making... 

Dianions.—Several examples of the growing interest in the use of dianions in synthesis have already been seen in this chapter. Dianions offer a way of increasing and diversifying the utility of long established materials such as ethyl acetoacetate, providing a new regiospecificity which was not formerly available. Thus Knight ° has found that furoic acids can form dianions as shown in Scheme 4, and typical reactions are illustrated. 

Ethyl acetoacetate reacts with two equivalents of LDA to give a dianion. Draw the structure of the dianion. 

In an analogous fashion to the results with l-bromo-2-chloroethane, the treatment of the dianion from ethyl acetoacetate with l,4-dibromo-2-butene resulted in the generation of 2-alkylidenetetrahydrofuran 268 as a 1 1 mixture of olefin isomers in 75 % yield (Scheme 70). Hydrogenation of 268 gave 2,5-c/s-tetrahydrofuran 269. 

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