Benzoate ester, reduction

Treatment of the /3-keto ester 220 with sodium ethoxide at elevated temperature triggered off an epoxide ring opening by / -elimination that was followed by the desired Knoevenagel condensation to afford the tricyclic product 206 (Scheme 34). The enone moiety in the intermediate 221 did not show a propensity for deprotonation and, therefore, the ketone carbonyl function of the enone moiety was available for a Knoevenagel condensation. The reduction of the p-keto ester (206) to the corresponding diol was the next objective. Treatment of the TES-protected -keto ester (TES-206) with DIBAH afforded the diastereomeric diols 222 and 223 in a moderate diastereoselec-tivity in favour of the undesired diastereomer 222. The diastereomers were separated and the undesired diastereomer 222 was epimerized to 223 by a sequence that consists of Mitsunobu inversion and benzoate ester reduction [98, 99]. 

A benzoate ester can be cleaved in 60-90% yield by electrolytic reduction at -2.3... 

Benzoate esters of 2-en-l,4-diols undergo reductive elimination with sodium amalgam.306... 

Tire aldehyde has been shown to be an intermediate in reduction of aromatic esters in both acid [149] and alkaline solutions [148]. It can be trapped in good yield in the form of an acetal by reduction of benzoate esters in acetonitrile in the presence of chlorotrimethylsilane [150]. Intermediates in the reduction of diphcnyl-2,2 -dicarboxylate esters undergo a cyclization reaction to form 5,6-dthydroxyph-enanthrene [148]. 

Related oxidants that have been exploited to similar ends include l-(tert-butoxy)-l,2-benzoiodoxol-3(l//)-one292 and sodium bromate.293 Oxidation of benzyl ethers by l-(/erf-butoxy)-l,2-benzoiodoxol-3(l/f)-one followed by easy basic hydrolysis of the resultant benzoate ester provides a convenient alternative to the usual reductive deprotection. The reaction is carried out in the presence of alkali metal carbonates and the conditions are mild enough to be compatible with other hydroxyl protecting groups such as methoxymethyl, tetrahydropyranyl, TBS and acetate. 

The variable loss of the methoxy substitutent is in fact a feature common to most 2-methoxybenzoic acid derivatives and appears to stem from the ammonium ions which are generated on mixing of the acid with ammonia. Pretreatment with one equivalent of base prevents hydrogenolysis completely in most cases, although the reduced solubility of the carboxylate salt can lead to incomplete reduction. Potassium salts are reasonably soluble, but reduction of the benzoate esters may afford the best solution (see Section 3.4.3.T). 

Reduction ofC=C and C C Bonds Table 2 Reduction of Benzoate Esters by Metals in Liquid Ammonia ... 

Voltammetric data for ester reductions are available for several aromatic esters [51-54], and in particular cyclic voltammetry shows clearly that in the absence of proton donors reversible formation of anion radical occurs [51]. In dimethylfonnamide (DMF) solution the peak potential for reduction of methyl benzoate is —2.29 V (versus SCE) for comparison dimethyl terephthalate reduces at —1.68 V and phthalic anhydride at —1.25 V [4]. Half-wave potentials for reduction of aromatic carboxylate esters in an unbuffered solution of pH 7.2 are linearly correlated with cr values [51] electron-withdrawing substituents in the ring or alkoxy group shift Ei/o toward less negative potentials. Generally, esters seem to be more easily reducible than the parent carboxylic acids. Anion radicals of methyl, ethyl, and isopropyl benzoate have been detected by electron paramagnetic resonance (epr) spectroscopy upon cathodic reduction of these esters in acetonitrile-tetrapro-pylammonium perchlorate [52]. The anion radicals of several anhydrides, including phthalic anhydride, have similarly been studied [55]. 

It has also been reported that reduction of benzoate esters in dry acetonitrile leads to solvent interaction resulting in benzoylacetonitrile in good yield as in Eq. (16) [59] ... 

If the ester group is conjugated with a ir-electron system, alternative reduction processes can occur. Benzoate esters are reduced to the 1,4-dihydrobenzoates by sodium in the system NH3/THF/H20. For... 

Conversion to benzoate ester 96, obtained by conversion of 94 into the corresponding acid chloride 95 followed by addition of alcohol 91, then set the stage for macrolide formation. This cyclization was effected by deprotonation and intramolecular alkylation at the benzylic position in 41% yield. Desulfurization and concomitant reduction of the olefin then provided 0-methyl lasiodiplodin (97) in 68% yield. Although Tsuji was readily able to construct the six-membered ring at the proper oxidation level, the symmetry implicit in this strategy precluded the required differentiation of the phenolic hydroxyl groups. 

The degradation of o-, m-, and p-phthalates under denitrifying conditions has been examined (Nozawa and Maruyama 1988), and after an initial decarboxylation to benzoate followed the pathway for the anaerobic degradation of benzoate that has been noted above formation of the CoA ester, reduction to cyclohex-l-ene carboxylate, hydroxylation to 2-hydroxycyclohexane car-boxylate, and ring fission to pimelic acid that was further degraded by P-oxi-dation. 

Reduction of carboxylic acid esters. Esters are not reduced by sodium borohydride. However, if ethanedithiol is added (excess), most benzoate esters are reduced to benzyl alcohols in high yield. Thiophenol and ethylmercaptan do not share this property. Several aliphatic esters are also reduced by NaBH4 activated by HSCHjCHjSH. ... 

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