Pyruvate, methyl, condensation with

A) Ethyl Butyryl-Pyruvate 146 grams of ethyl oxalate are condensed with 86 grams of methyl-(n)-propyl-ketOne in the presence of sodium ethylate prepared from 25 grams of sodium. 135 grams of product, having a boiling point of 1l3°C/6 mm, are obtained. 

Evans also investigated the aldol condensation between methyl pyruvate 151 and several different substituted enol ethers 152, again using bu-box 3 and copper(II) triflate. These reactions achieved selectivities up to 98 2 (syn/anti) with syn ee up to 98% and yields up to 96% (Table 9.27, Fig. 9.47h). " ... 

However, the presence of a negative group is not always necessary 3-phenyl-5-methyl oxadiazole reacts with benzaldehyde in the presence of zinc chloride to give j8(phenyl-3-oxadiazolyl)styrene. With ethyl oxalate (phenyl-3-oxadiazolyl) pyruvate is formed in a Claisen condensation. 

The title compounds were also synthesized from quinazoline precursors through the formation of their 1,4-oxazine rings. N-Methylisatoic anhydride was first condensed with ethanolamine to give N-(2-hydroxyethyl)-2-methylaminobenzamide (580). Cyclization of the latter with ethyl pyruvate gave quinazoline derivatives 581 which, upon hydrolysis and dehydrative cyclization with l-methyl-2-chloropyridinium iodide, afforded the l,4-oxazines[3,4- ]quinazoline (582) (8QJHC1163). 

The third type of carbon-branched unit is 2-oxoisovalerate, from which valine is formed by transamination. The starting units are two molecules of pyruvate which combine in a thiamin diphosphate-dependent a condensation with decarboxylation. The resulting a-acetolactate contains a branched chain but is quite unsuitable for formation of an a amino acid. A rearrangement moves the methyl group to the (3 position (Fig. 24-17), and elimination of water from the diol forms the enol of the desired a-oxo acid (Fig. 17-19). The precursor of isoleucine is formed in an analogous way by condensation, with decarboxylation of one molecule of pyruvate with one of 2-oxobutyrate. 

Likewise, such functional derivatives of V-acetylmannosamine as the 6-acetate (16), the 6-(L-lactate) 17, and the 4- and 6-methyl ethers, 18 and 19, condensed with pyruvate, gave,20 in good yields, acids 20, 21, 22, and 23. 

Medium Boiling Esters. Esterification of ethyl and propyl alcohols, ethylene glycol, and glycerol with various acids, eg, chloro- or bromoacetic, or pyruvic, by the use of a third component such as benzene, toluene, hexane, cyclohexane, or carbon tetrachloride to remove the water produced is quite common. Benzene has been used as a co-solvent in the preparation of methyl pyruvate from pyruvic acid (101). The preparation of ethyl lactate is described as an example of the general procedure (102). A mixture of 1 mol 80% lactic acid and 2.3 mol 95% ethyl alcohol is added to a volume of benzene equal to half that of the alcohol (ca 43 mL), and the resulting mixture is refluxed for several hours. When distilled, the overhead condensate separates into layers. The lower layer is extracted to recover the benzene and alcohol, and the water is discarded. The upper layer is returned to the column for reflux. After all the water is removed from the reaction mixture, the excess of alcohol and benzene is removed by distillation, and the ester is fractionated to isolate the pure ester. 

The S-methyl compound (140) (R = Me), when treated with aminoacetal 152, yielded imidazodiazocine 153 (R = H). If, in addition, various electrophiles are added, such as aroyl isothiocyanates and aroyl chlorides, N-substituted compounds 153 (R = CONHC6H3R2 (R2 = Cl, Me) 3,4,5-(OMe)3C6H2CO, and 5-N02-2-furyl] are obatined [761JC(B)773]. Reaction of isoureas 113 (R = Me, Et) or isothioureas 140 (R = Me, Et) with hydrazine gave 106 (R = NH2). The latter compound was condensed with pyruvate or 2-ketophenylacetate esters to afford diazocino-l,2,4-triazinones 154 (R = Me, Ph) (72LA112). 

The AAamino-2-oxazolidinone 2a was condensed with methyl pyruvate (44) to give hydrazone 45 (Scheme 10) as an E/Z mixture (dr 92 8), from which the minor (Z)-isomer was removed via flash chromatography to give pure ( )-45 in 75%... 

A completely different product outcome is observed with enamides derived from a-ketoesters12. Benzoylation of the product obtained by condensation of methyl pyruvate with benzyl amine led to the formation of enamide 21 (Scheme 6). Irradiation of 21 in methanol produced only a 10% yield of the expected cyclization product 22,... 

The methyl group of pyruvic acid, CHjCOCOjH, undergoes condensation with aldehydes to give olefinic a-keto acids. Directions for improved yields are given for benzalpyruvic acid, QHsCH=CHCOCOjH (80%). Aromatic aldehydes containing alkyl and alkoxyl groups, as well as olefinic aliphatic aldehydes and furfural, have been condensed. 

Table 2. Condensation of D-glycopyranosides 11 with methyl pyruvate under BFj-catalysis starting material 11 product 12 yield starting material 11 product 12 yield...

Pyruvate ketals can be synthesized [161] by direct condensation of a pyruvate ester with a diol in the presence of a Lewis acid, but this is less preferred because of the electron-withdrawing effect of the adjacent carboxylate group [162,163]. Therefore, several indirect methods for the acetalization have been introduced including condensation with pyruvate derivatives [164,165] or generation of the carboxylate group by oxidation of a suitable precursor [166,167,168,169]. A more efficient route to pyruvic acid acetals starts from silylated diols [170] or by the reaction between diols and methyl pyruvate dialkyl dithioacetal [171,172] activated by methyl triflate, dimethyl(methylthio)sulfonium trifluoromethane sulfonate (DMTST), nitroso tetraflu-oroborate (NOBF4), S02Cl2-trifluoromethanesulfonic acid, or Al-Iodosuccinimide (NIS) and trifluoromethanesulfonic acid [173] (O Scheme 24). 

The first efforts to address this issue involved hydrazone ( ) 62 (Scheme 2.9), prepared as a mixture E/Z 92 8) and separated via flash chromatography as the pure ( ) isomer in 75% yield. In this preparation, the oxazolidinone N amination was accomplished using a solution of monochloramine in methyl tert butyl ether [45], furnishing a quantitative yield of the N amino 2 oxazolidinone, which in turn was condensed with methyl pyruvate to afford 62. Addition of ethyl iodide to ( ) 62 using the Mn mediated photolysis conditions as described above gave 66% yield ofthe ethyl adduct, with a modest diastereomer ratio of 70 30, while the correspond ing isopropyl addition was very effective (85% yield, dr 92 8). Variation in the stoichiometry indicated that amounts less than 2 equiv of Lewis acid proportionally lowered the diastereoselectivity, suggesting that, in this case, the ester may participate... 

The original report of the condensation of ethyl pyruvate (MeC0C02Et) with 3,4-diaminopyridine contained several errors. The confusion resulting from this has now been clarified,and a correction has appeared. The reaction in ethanol of ethyl pyruvate and 3,4-diaminopyridine gives a mixture of the 2-methyl-3-oxo compound 33... 

Complimentary diastereoselectivities have been observed in condensations of methyl pyruvates with various organometallic nucleophiles, the allylborane (142) giving largely the threo- adducts... 

There are countless synthetic examples of the aldol condensation. In one example taken from Massanet s synthesis of eudesmanolides, diketone 134 was converted to the enolate anion with LDA. In a second step, methyl pyruvate was added to give a 98% yield of 135 and 136 in about a 1 1 ratio. 

The pyrido[3,2-rf]pyrimidine (135) was prepared by condensation of the pyrimidinedione (133) with an a-oxoester such as methyl pyruvate or ethyl mesoxalate, or with diethyl oxalate, in the presence of a base. Presumably the reaction involves initial condensation to give the imine (134) as shown in Scheme 29 (57CB728) (cf. Section VIII). 

Chaetomellic acids have been the subject of a number of syntheses. In 1993, we reported the first synthesis of chaetomellic acid A based on the biogenetic type aldol condensation [73]. The aldol reaction of appropriate fatty acid methyl esters with methyl pyruvate yielded two diastereomeric... 

Although a great number of alkaloids having a /8-carboline structure have been found in nature, very few reports have been published about their biogenesis, and these are concerned only with the plant material. From among the alkaloids mentioned above only harman (180) and 4,5-dihydrocanthin-6-one (181) were demonstrated in feeding experiments with H- and C-labeled precursors to be derived biosynthetically from tryptophan. In the case of harman, tryptamine is probably condensed with pyruvic acid to give l-methyl-l,2,3,4-tetrahydro-j8-carboline-l-carboxylic... 

A similar conclusion can be drawn from an unexplained case of sonochemical switching (Fig. 29). The addition of primary aromatic amines to methyl pyruvate produces first the tautomeric imine-enamine condensation product. This step seems to be sonication independent. Under stirring at room temperature, the condensation goes on with the condensation of the enamine with the pyruvic ester to yield a lactone. In contrast, sonication under the same conditions... 

Our typical preparation method for these perfluorodioxolane monomers and polymers is shown in Scheme 16.5 [13-18]. Commercially available methyl pyruvate and diols are used as the starting materials. The condensation product is then directly fluorinated in a fluorinated solvent such as Fluorinert FC-75 by the F2/N2 mixture. After flushing the system using nitrogen gas for 1 hour, fluorine gas diluted to 20% with nitrogen is blown into the reaction mixture at a flow rate of 240 L/h. The reaction is carried out at a temperature of around 25°C for over 20 hours. After the reaction is over, the mixture is neutralized with aqueous potassium hydroxide solution. The... 

One of the most efficient and simplest routes for the fabrication of these perfluorodioxolane monomers and polymers is shown in Scheme 4.3 [26-30]. Commercially available methyl pyruvate and diols are used as the starting materials. The condensation product is then directly fluorinated in a fluorinated solvent such as Fluorinert FC-75 (3M) with a F2/N2 mixture. After flushing the system with nitrogen gas for 1 h, fluorine gas diluted to 20% with nitrogen is blown into the reaction mixture at a flow rate of 2401/h. The reaction is carried out at approximately 25 C for over 20 h. After the reaction is complete, the mixture is neutralized with aqueous potassium hydroxide. The crude monomer is isolated upon decarboxylation of the potassium salt and then purified by fractional distillation. The fluorination process is the key step in the synthesis. The yield is as high as 75% with careful control of the fluorination temperature, and it depends on the structure of the hydrocarbon precursor. Recently, over 90% yield of the fluorination of similar compounds has been reported [31]. The polymerization of these monomers is generally carried out in bulk at 60 - 80 °C for 24-35 h using perfluorodibenzoyl peroxide as the initiator [32]. The conversion yields are 70-80%, and the polymers obtained are colorless and transparent. 

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