Keto esters dianions

The most important esters in connection with Li batteries are y-butyrolactone (BL) and methyl formate (MF). Li is apparently stable in both solvents due to passivation. Electrolysis of BL on noble metal electrodes produces a cyclic 0-keto ester anion which is a product of a nucleophilic reaction between a y-butyrolactone anion (produced by deprotonation in position a to the carbonyl) and another y-BL molecule. FTIR spectra measured from Li electrodes stored in y-BL indicate the formation of two major surface species the Li butyrate and the dilithium cyclic P-keto ester dianion. The identification of these products and related experimental work is described in detail in Refs. 150 and 189. Scheme 3 shows the reduction patterns of y-BL on lithium surfaces (also see product distribution in Table 3). In the presence of water, the LiOH formed on the Li surfaces due to H20 reduction attacks the y-BL nucleophilically to form derivatives of y-hydroxy butyrate as the major surface species [18] [e.g., LiO(CH2COOLi)]. We have evidence that y-BL may be nucleophilically attacked by surface Li20, thus forming LiO(CH2)3COOLi, which substitutes for part of the surface Li oxide [18]. MF is reduced on Li surfaces to form Li formate as the major surface species [4], LiOCH3, which is also an expected reduction product of MF on Li, was not detected as a major component in the surface films formed on Li surfaces in MF solutions [4], The reduction paths of MF on Li and their product analysis are presented in Scheme 3 and Table 3. 

An alternative procedure for (3-keto ester dianion formation involves deprotonation of H - using one equivalent of NaH followed by deprotonation of an using either MeLi or n-BuLi. This method is especially useful in cases where the a-posi-tion is too hindered for deprotonation by LDA. ... 

Keck, G. E., Yu, T. Catalytic Asymmetric Allylation Reactions Using BITIP Catalysis and 2-Substituted Allylstannanes as Surrogates for P-Keto Ester Dianions. Org. Lett. 1999,1, 289-291. 

The method of Huckin and Weiler has enjoyed widespread use in synthesis. For example, recently reported syntheses of rrans-bicyclo[4.3.1]decan-10-one and a bicyclo[4.4.1]undecan-7-one derivative have employed y-alkylations of 3-keto ester dianions as key steps. This methodology has also been extended to the formation and y-alkylation of dianions of y,8-unsaturated P-keto esters. ... 

An attractive procedure for the preparation of 2-oxo-m-(alkoxycarbonyl)alkylphosphonatcs involves the C-phosphonylation of p-keto ester dianions with dialkyl chlorophosphate (45-67%) or C-phosphirylation of the monoanion of substituted dioxinones with diethyl chlorophosphite followed by oxidation ... 

Dicarbonyl compounds may be converted into dianions, which react with electrophiles at the more basic site. Huckin and Weiler found that 3-keto ester dianions undergo aldol addition reactions at the more basic methyl position (equation 32). The lithium/sodium dianion shows surprisingly weak reactivity, giving the aldol in only 11% yield after 1 h at -78 °C In contrast, the lithium enolates of simple ketones and esters, which should be much less basic than the 3-keto ester dianion, react with aldehydes to give nearly quantitative yields of aldols in THF in seconds at -78 °C. ° Seebach and Meyer also studied this reaction, and obtained the oxolactone (equation 33). Simple diastereoselection in the reaction of 3-keto ester dianions has also been studied (vide infra). 

The foregoing reactions bear a resemblance to the reactions of 3-keto ester dianions vide supra, equation 32), in that reaction occurs at C-4 instead of C-2. The only study of simple diastereoselection in the aldol reactions of 3-keto ester dianions shows a stereochemical similarity as well. As shown in equation (84), the dianions of a series of 3-keto esters react with aldehydes to give largely the trans lactone (126) data are summarized in Table 10. ° ... 

Weiler et al have employed their jS-keto-ester dianion y-alkylation technique to produce, in one step, 5-alkoxy-j8-keto-esters of known utility in Robinson-type annelation sequences. ... 

The 1.3-allylic diacetate 135 can be used for the formation of the methy-lenecyclopentane 137 with the dianionic compound 136(86]. The cyclohexa-none-2-carboxylate 138 itself undergoes a similar annulation with the 1,3-allylic diacetate 135 to form the methylenecyclohexane derivative 139(90]. The reaction was applied as a key step in the synthesis of huperzin A[91]. On the other hand. C- and 0-allylations of simple J-dikctones or. 1-keto esters take place, yielding a dihydropyran 140(92]. 

Scheme 65 summarizes Mori s synthesis of 44 [97]. Reduction of keto ester A with baker s yeast gave hydroxy ester B of about 98% ee. Methylation of the dianion derived from B diastereoselectively gave C, which was converted to 44. This process enabled the preparation of about 10 g of (lS,5R)-44. 

In the case of mono-ester substituted pyrroles (e.g., 68) wherein relatively unstable dianions likely to deprotonate ammonia might be produced, the authors instead utilized an excess of (MeOCH2CH2)2NH as a substitute for ammonia. It was felt that upon in situ formation of (MeOCH2CH2)2NLi, this base would be unable to protonate the dianion <00TL1331>. Remarkably, quenching the reduction reactions with benzoyl chloride affords P-keto esters (e.g., 69, R = COPh), a reaction that does not occur when conducted in liquid ammonia. 

In an amazing reaction, dissolving metal reduction of dichloro diester 859 generates dianion 860 which can be conventionally methylated (Scheme CIII) Irradiation of keto ester 861 introduces yet another framework bond. Dehydration of the newly... 

Paquette and coworkers have demonstrated that monoalkylation of dianion 860 proceeds with a kinetic preference for electrophilic capture at the ester enolate site. Thus, addition of. limited amounts of methyl iodide to 860 affords %8 in 46 % isolated yield With this keto ester in hand, it proved an easy matter to elaborate... 

Selective alkylation of 6-keto esters via either anions or dianions is an important synthetic transformation. Equally, thioesters may be trans-esterified in the presence of thiophilic metal cations. These two features... 

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 sulfenylation of metalloimines is equally applicable to ketones, although using more reactive sulfur electrophiles it is possible to bring about reaction on the unmetallated enamine. ° Sulfenylation of ketone enol silyl ethers also proceeds well with the more reactive sulfur species. Sulfenamides and their derivatives e.g. 11) are particularly suited to the direct sulfenylation of ketones and active methylene compounds such as -diketones, -keto esters and malonates, which undergo facile reaction at room temperature (equation 5). This procedure, however, does not appear to have been exploited for the dehydrogenation of active methylene compounds icf. Section 2.2.4.1). By preparing the dianion (13)... 

A general synthetic route toward the marine metabolite eunicellin diterpenes was developed by G.A. Molander and co-workers.The power of this method was demonstrated by the completion of the asymmetric total synthesis of deacetoxyalcyonin acetate. A tricyclic (3-keto ester intermediate was methylated in the y-position with complete diastereoselectivity using dianion chemistry and the crude product was subjected to the Krapcho decarboxylation. This was one of the rare cases when the transformation did not only remove the methoxycarbonyl group, but at the same time epimerized the newly formed stereocenter to yield a separable mixture of methyl ketones. 

Lygo, B. Reaction of aziridines with dianions derived from p-keto esters application to the preparation of substituted pyrrolidines. Synlett 1993, 764-766. 

The group of Tietze has described syntheses of variously substituted pyrazolones 20 starting from solid-phase-bound p-keto esters. Single or iterative alkylation of the dianion of immobilized acetoacetate with allyl-, benzyl- or alkyl halides produced a set of y-substituted ketoesters 18 that could be transformed to the phenyl-hydrazones 19. Treatment of these intermediates in toluene at 100 °C produced 1-phenylpyrazolone derivatives 20 in 40-75% yield (Scheme 6) [14]. 

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 word about the synthesis of the a-series, a-geraniol (73) and a-nerol (74), is warranted because they are often intermediates in the synthesis of 1-hydroxylated compounds (e.g., some diols described below). Weiler has continued his exploitation of the dianion of methyl acetoacetate to this end. Instead of prenylation (Vol. 4, p. 461, Ref. 73) he carried out a similar series of operations by alkylating the dianion with 4-bromo-2-methyl-l-butene, thus arriving at compounds of the a-series via the keto ester 75, methylating the enol phosphate to 76. He also prepared the double methylene isomer 77 (R = COEt) of geranyl propionate from the intermediate 75. The purpose of synthesizing this propionate was to prepare the pheromone of the San Jose scale, Quadraspidiotus pernicious, which is a mixture of the propionates of 73, 74,... 

The Claisen condensation of a 1,3-diketone, via its dianion, with an ester, °° or of a ketone enolate with an alkyne ester, also give the desired tricarbonyl arrays. Applying this principle to 1,3-keto-esters leads through to 2,4-dioxygenated heterocycles. ... 

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