Ester anion formation

Evidence of ester anion formation according to equation 7 has been reported in the literature. Other strongly basic catalysts such as the triphenylmethyl carbanion can be used. ... 

The effect of a substituent may be substantially modified by fast, concurrent, reversible addition of the nucleophile to an electrophilic center in the substituent. Ortho- and para-CS.0 and pam-CN groups have been found by Miller and co-workers to have a much reduced activating effect on the displacement of halogen in 2-nitrohaloben-zenes with methoxide ion [reversible formation of hemiacetal (143) and imido ester anions (144)] than with azide ion (less interaction) or thiocyanate (little, if any, interaction). Formation of 0-acyl derivatives of 0x0 derivatives or of A-oxides, hydrogen bonding to these moieties, and ionization of substituents are other examples of reversible and often relatively complete modifications under reaction conditions. If the interaction is irreversible, such as hydrolysis of a... 

The mixed Claisen condensation of two different esters is similar to the mixed aldol condensation of two different aldehydes or ketones (Section 23.5). Mixed Claisen reactions are successful only when one of the two ester components has no a hydrogens and thus can t form an enolate ion. For example, ethyl benzoate and ethyl formate can t form enolate ions and thus can t serve as donors. They can, however, act as the electrophilic acceptor components in reactions with other ester anions to give mixed /3-keto ester products. 

R2=MeC>2C, R3 = d-F CC F ), regioisomeric 4-trifluoromethyl-5-isoxazole-carboxylates, 213 (R1 =Me02C, R2 =CF3, R3 = 4-F3CC6H4) and unexpectedly oximinoyl chloride 214, resulted by 1,4-addition. Product distribution is rationalized in terms of two competing reactions, either 1,4-addition of the oximate anion to the acetylenic ester or formation of the nitrile oxide followed by 1,3-dipolar cycloaddition. Anionic 1,4-addition of the oximinoyl chloride to the acetylenic ester is favoured at low temperatures, while nitrile oxide formation, followed by cycloaddition, occur at temperatures above 0 ° (371). 

An enolate anion generated from a carboxylic acid derivative may be used in the same sorts of nucleophilic reactions that we have seen with aldehyde and ketone systems. It should be noted, however, that the base used to generate the enolate anion must be chosen carefully. If sodium hydroxide were used, then hydrolysis of the carboxylic derivative to the acid (see Section 7.9.2) would compete with enolate anion formation. However, the problem is avoided by using the same base, e.g. ethoxide, as is present in the ester... 

The racemization process involves removal of the a-hydrogen to form the enolate anion, which is favoured by both the enolate anion resonance plus additional conjugation with the aromatic ring. Since the a-protons in esters are not especially acidic, the additional conjugation is an important contributor to enolate anion formation. The proton may then be restored from either side of the planar system, giving a racemic product. 

In this case, we formulate the Claisen reaction between two ester molecules as enolate anion formation, nucleophilic attack, then loss of the leaving group. Now reverse it. Use hydroxide as the nucleophile to attack the ketone carbonyl, then expel the enolate anion as the leaving group. All that remains is protonation of the enolate anion, and base hydrolysis of its ester function. 

The mechanistic steps can be deduced by inspection of structures and conditions. Enolate anion formation from diethyl malonate under basic conditions is indicated, and that this must attack the epoxide in an Sn2 reaction is implicated by the addition of the malonate moiety and disappearance of the epoxide. The subsequent ring formation follows logically from the addition anion, and is analogous to base hydrolysis of an ester. Ester hydrolysis followed by decarboxylation of the P-keto acid is then implicated by the acidic conditions and structural relationships. 

A palladium-cataly/ed C-C coupling reaction—the Heck reaction — is used in the construction of bicyclic system 13. Cyclization leads to a q3-alIyl-Pd complex, which undergoes nucleophilic attack by malonic ester anion 12. This in turn leads to formation of the C4 side chain The mechanism of this reaction therefore differs from that of a normal Heck reaction. 

However, use of an ester group could activate this position toward anion formation and thus we could write instead... 

Scheme 68) <86H(24)1565>. The most likely mechanism of this reaction involves radical anion formation (414), cleavage, successive electron addition, and cyclization of the intermediary imido-ester (415) to an imidazole derivative (416) (Scheme 68). 

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. 

Compound I features three carbonyl centers of various degrees of reactivity. It also displays a potentially acidic proton on the carbon between the /3-keto ester and lactone carbonyls. In principle, the carbanion derived therefrom should be comparable to the useful /3-keto ester anions in nucleophilic substitutions and additions that lead to the formation of C-C bonds. Diethyl oxaloacetate, however, is a very poor nucleophile, because epoxides and enones remain unaltered in its presence. This peculiarity poses severe restrictions to the synthetic applications of this reaction. 

Efficient enantioselective alkylations are known.In another method enantio-selective alkylation can be achieved by using a chiral base to form the enolate. Alternatively, a chiral auxiliary can be attached. Many auxiliaries are based on the use of chiral amides ° or esters.Subsequent formation of the enolate anion allows alkylation to proceed with high enantioselectivity. A subsequent step is... 

In the absence of protons the deprotection is complicated by nucleophilic attack of RO on the tosylate ester with formation of the ether, ROR [Eq. (60)]. This side reaction can be suppressed on addition of a proton donor, such as acetic acid. In that case aromatic radical anions cannot be used as catalyst and Ni(acacen) was used. The difference in yield of deprotected alcohol from direct and indirect reduction was insignificant [249]. 

C-Phosphorylated malonic acid derivatives are conveniently obtained by the acylation of phosphonoacetic ester anions with chloroformic esters. Further consideration has been given to the formation (and properties) of A -l,4,2-oxaza-phospholine 2-oxides (44) by cyclization of a-benzamidovinylphosphinic esters with PClg. ... 

When primary or secondary amides are treated with a base, there is a complicating reaction that was not possible with esters, ketones, or aldehydes. The N—H moiety is acidic enough to react with the bases used for deprotonation. Treatment of 56 with base gave the A-lithio derivative, but the a-lithio derivative (57) can be generated by addition of two equivalents of base. Enolate anion formation is straightforward with tertiary amides, such as dimethylisobutyramide (56, R = Me) and the resultant enolate anion (58) reacted with butanal to give amido-alcohol 59 in 68% yield O (see sec. 9.4.B). 

To avoid the B-elimi nation neopentyl alkyl sulfonates were subjected to the alkyl nitration. The results summarized in Table XI indicate that the yields of nitration decrease with lengthening of the chain. To obtain optimun yields of a-nitrosulfonate esters containing 8-12 carbons in the chain more concentrated reaction mixtures had to be employed (instead of 250 ml, only 100 ml of liquid ammonia was used). In the case of the C-]2"Sulfonate the yield was only 3% when the nitration was carried out in 250 ml of liquid ammonia. The yield increased ten-fold to 33% when the reaction was performed in only 100 ml of ammonia. It is likely that the low yield was due to a slower rate of anion formation. In fact the yield was increased from 33% to 47% when the anion of the Ci2 Sulfonate was generated with KNH2 in THF at 65° and then nitrated at -40. The Ci6-sulfonate did not undergo nitration at all. This was due to a lack of anion formation. Even when the compound was treated with KNH2 in THF at 65 , no deuterium was... 

We also were successful in applying the alkyl nitrate nitration to TT-deficient heterocyclic compounds such as 2- and 4-meth-ylpyridines, 4-methyl pyrimidine, and to ir-excessive heterocyclics such as 2-methylbenzoxazole and 2-methylbenzothiazole (15). Both sodium and potassium amides in liquid ammonia were found to be effective as bases. In the KNH2-JI.NH3 system optimum yields are obtained if the molar ratio of base to substrate to nitrate ester is 2.0 1.0 2.5. After allowing 2-3 minutes for anion formation the nitrate ester is added as rapidly as possible while maintaining the temperature below -33°. Next the ammonia is replaced with ether and the nitro salt filtered off and acidified with aqueous acetic acid. 

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