Diesters reaction with sodium

Recently, the intramolecular nitrile oxide-alkene cycloaddition sequence was used to prepare spiro- w(isoxazolines), which are considered useful as chiral ligands for asymmetric synthesis (321). Reaction of the dibutenyl-dioxime (164) (derived from the diester 163) with sodium hypochlorite afforded a mixture of diastereomeric isoxazolines 165-167 in 74% combined yield (Scheme 6.80) (321). It was discovered that a catalytic amount of the Cu(II) complex 165-Cu(acac)2, where acac = acetylacetonate, significantly accelerated the reaction of diisopropylzinc... 

Unsaturated diesters are readily converted into carboxylic keto-esters by their reaction with sodium cyanide (Scheme 62). ... 

All these compounds are made by - esterifleation of the corresponding alcohols or ethoxylates with maleic acid anhydride (monoesters are obtained at 70-100 °C, tgdiile diester formation needs higher temperatures and an azeotropic elimination of water) and subsequent reaction with sodium hydrogen sulfite. All s. have one property in common they are sensitive to - hydrolysis and can be used only in neutral media (pH 6-8). 

Whereas condensation of a-hydroxy ketones such as benzoin and acetoin on heating with formamide [240] or ureas in acetic acid [239, 242] to form imidazoles such as 769 or 770 is a well known reaction, only two publications have yet discussed the amination of silylated enediols, prepared by Riihlmann-acyloin condensation of diesters [241], by sodium, in toluene, in the presence of TCS 14 [241, 242]. Thus the silylated acyloins 771 and higher homologues, derived from Riihl-... 

In this section primarily reductions of aldehydes, ketones, and esters with sodium, lithium, and potassium in the presence of TCS 14 are discussed closely related reductions with metals such as Zn, Mg, Mn, Sm, Ti, etc., in the presence of TCS 14 are described in Section 13.2. Treatment of ethyl isobutyrate with sodium in the presence of TCS 14 in toluene affords the O-silylated Riihlmann-acyloin-condensation product 1915, which can be readily desilylated to the free acyloin 1916 [119]. Further reactions of methyl or ethyl 1,2- or 1,4-dicarboxylates are discussed elsewhere [120-122]. The same reaction with trimethylsilyl isobutyrate affords the C,0-silylated alcohol 1917, in 72% yield, which is desilylated to 1918 [123] (Scheme 12.34). Likewise, reduction of the diesters 1919 affords the cyclized O-silylated acyloin products 1920 in high yields, which give on saponification the acyloins 1921 [119]. Whereas electroreduction on a Mg-electrode in the presence of MesSiCl 14 converts esters such as ethyl cyclohexane-carboxylate via 1922 and subsequent saponification into acyloins such as 1923 [124], electroreduction of esters such as ethyl cyclohexylcarboxylate using a Mg-electrode without Me3SiCl 14 yields 1,2-ketones such as 1924 [125] (Scheme 12.34). 

Another important reductive coupling is the conversion of esters to a-hydroxyketones (acyloin condensation).267 This reaction is usually carried out with sodium metal in an inert solvent. Good results have also been obtained for sodium metal dispersed on solid supports.268 Diesters undergo intramolecular reactions and this is also an important method for the preparation of medium and large carbocyclic rings. 

Differentiation between the secondary hydroxyl groups in methyl 4,6-O-benzylidene-a-D-glucopyranoside was observed on reaction with methyl benzoate-sodium methoxide at 200° for 45 minutes the 2- and 3-esters and the 2,3-diester were formed176 in the molar ratios of 55 23 10. 

Among the methods described in Section 10.6.5, the syntheses reported by Umezawa et alJ78 and Garcfa-Lopez et al.179,80 have been most widely used. As summarized in Scheme 33, the synthesis is initiated with the preparation of a diazo ketone through the reaction between a N-protected a-amino acid and isobutyl chloroformate followed by treatment with diazomethane. The chloromethyl ketone is prepared by adding 2.5 M hydrochloric acid to the diazo ketone. Transhalogenation is exploited to obtain the iodomethyl ketone. Through in situ reaction with the sodium derivative of dimethyl malonate, the 4-oxo diester is obtained. 

Dehydrohalogenation sometimes leads to cyclization which gives cycloalkanes or heterocycles. The fluorinated diester 1 has proved to be a convenient source of polyfluoroalkylated cyclopropanes. Reaction of 1 with aqueous potassium hydroxide gives 2- HA //-hepta-fluorobutyl)cyclopropane-l, 1 -dicarboxylic acid (2) in quantitative yield.120 The diethyl ester 3 ot this acid is obtained in a yield of 87% by the reaction of 1 with sodium ethoxide in anhydrous ethanol.120... 

The reaction of esters with sodium in ethanol is referred to as the Bouveault-Blanc reaction. Prior to the discovery of complex metal hydrides, this reaction was the only method for the reduction of esters to alcohols. The diesters shown in Figure 17.59 produce a diol in this way. 

The so-called acyloin condensation consists of the reduction of esters—and the reduction of diesters in particular—with sodium in xylene. The reaction mechanism of this condensation is shown in rows 2-4 of Figure 14.51. Only the first of these intermediates, radical anion C, occurs as an intermediate in the Bouveault-Blanc reduction as well. In xylene, of course, the radical anion C cannot be protonated. As a consequence, it persists until the second ester also has taken up an electron while forming the bis(radical anion) F. The two radical centers of F combine in the next step to give the sodium glycolate G. Compound G, the dianion of a bis(hemiacetal), is converted into the 1,2-diketone J by elimination of two equivalents of sodium alkoxide. This diketone is converted by two successive electron transfer reactions into the enediolate I, which is stable in xylene until it is converted into the enediol H during acidic aqueous workup. This enediol tautomerizes subsequently to furnish the a-hydroxyketone—or... 

Cyclopentanones. The reaction of the sodium enolate of the keto diester 2 with 1 in THF at 20° leads to the cyclopentene 3 in 90% yield. The product is readily converted to the ketone 4 by treatment with TFA. 

The open-chain tautomers 24b and 25 of precursor incipient imidazolidine and perhydropyrimidine derivatives, which bear a six carbon transferable fragment, on acid-catalyzed reactions with tryptamine formed the diester 85. A similar reaction of 24a leads to quantitative formation of 86 and the reaction of 25 with tryptamine is appreciably faster than that of 24b. Sodium cyanoborohydride/acetic acid reduction of 85 was accompanied by intramolecular aminolysis to form piperidone 87. Its Bischler-Napieralski cyclization followed by borohydride reduction gave cis- and trara-isomers of indoloquinolizine ester 88, which on hydrolysis to acid and subsequent methylene lactam rearrangement gave methylene lactam 89. Its DIBAL reduction gave 18- or-deplancheine 84a (88T6187). 

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