Benzyl pyruvate

Harada and Matsumoto studied the effect of solvents on the % ee of the amino acids formed in asymmetric transamination.56 Generally, the optical activity of alanine prepared from benzyl pyruvate and (S )-)-)-1-phenylethylamine decreased with increasing polarity of the solvents used. From the finding that sodium a-phenylglycinate was hydrogenolyzed easily to ammonia and phenylacetate over palladium catalyst, Harada prepared optically active alanine, butyrine, glutamic acid, and aspartic acid in 40-60% optical purities from the corresponding a-oxo... 

Amino acids can be synthesized via the coupling of Schiff bases with carbanions generated by reduction of benzyl halides [143,144]. Electrolysis of benzyl chloride at mercury in DMF containing TBABr, and in the presence of the Schiff base formed from benzylamine and benzyl pyruvate, affords or-methylphenylalanine in up to 86% yield (after hydrogenolysis over palladium-charcoal). An antihypertensive agent, or-methyl-j6-(3,4-dihydroxyphenyl)alanine, has been prepared by reductive coupling of the aforementioned Schiff base with 3,4-methylenedioxybenzyl chloride. 

An enantioselective version of the above reactions has been reported. Lewis acids such as Yb(OTf)3 can profoundly affect the stereochemical outcome of the carbonyl ylide 1,3-dipolar cycloadditions [137]. This provided an indication to effect asymmetric carbonyl ylide cycloaddition using a chiral Lewis acid. The first example of such asymmetric induction using the chiral lanthanide catalysts has been reported [138,139]. For example, the reaction of diazoacetophenone 89 with benzyloxyacetaldehyde, benzyl pyruvate and 3-acryloyl-2-oxazoHdinone in the presence of chiral 2,6-bis(oxazolinyl)pyridine ligands and scandium or ytterbium complexes furnished the corresponding cycloadducts 165-167 with high enantioselectivity (Scheme 53). 

In contrast to the diastereoselectivity of the reaction with benzyloxyacetaldehyde derivatives, the Sc(III)-(5, 5)-PyBOX-catalyzed cycloadditions of 2-benzopyrylium-4-olate with methyl and benzyl pyruvate showed high exoselectivity (Scheme 7.26 and Table 7.20). This is probably attributed to the unfavorable dipolar interactions between the carbonyl groups of 2-benzopyrylium-4-olate and the ester in the eniio-approach. However, the maximum enantiomeric excess of the exo-adduct was only 56% ee when (S,S)-PyBOX-TPSm was used as a ligand (Figure 7.3 and Table 7.20, entry 3). After several attempts to increase the enantioselectivity, both diastereo- (up to exo endo = 96 4) and enantioselectivities (up to 87% ee (exo)) were determined to improve in the Sc(III)-(5,5)-PyBOX-i-Pr-catalyzed reaction (up to 94% yield) when pyruvic acid was used as an additive (entries 5, 6, 8, and 9). By the examinations of some... 

In current industrial practice, benzaldehyde is added to fermenting baker s yeast Saccharomyces cerevisiae) with resultant PAC production occurring from the yeast-derived pyruvate. Typically PAC concentrations of 12-15 g F are produced at yields of 65-70% theoretical in a 10-12 h biotransformation process. [2], Appreciable concentrations of benzyl alcohol are produced as by-product due to oxidoreductase activity in the fermentative yeast. 

An enzymatic process using partially purified pyruvate decarboxylase (PDC) with added pyruvate overcomes the problems of benzyl alcohol formation and limiting availability of pyruvate [3]. As a result increased concentrations, yields and productivities of PAC were achieved with concentrations of PAC in excess of 50 g f (330 mM) in 28 h and yields on benzaldehyde above 95% theoretical [4-6]. Screening of a wide range of bacteria, yeasts and other fungi as potential sources of stable, high activity PDC for production of PAC confirmed a strain of the yeast Candida utilis as the most suitable source of PDC [7]. 

A crystal structure of the C02 derivative of (8), K[Co(salen)( 71-C02)], haso been reported in which the Co—C bond is 1.99 A, the C—O bonds are both equivalent at 1.22 A and the O-C-O angle is 132°.125 Carboxylation of benzylic and allylic chlorides with C02 in THF-HMPA was achieved with (8) electrogenerated by controlled-potential electrolysis,126 in addition to reductive coupling of methyl pyruvate, diethyl ketomalonate and / -tolylcarbodiimide via C—C bond formation. Methyl pyruvate is transformed into diastereomeric tartrates concomitant with oxidation to the divalent Co(salen) and a free-radical mechanism is proposed involving the homolytic cleavage of the Co—C bond. However, reaction with diphenylketene (DPK) suggests an alternative pathway for the reductive coupling of C02-like compounds. 

Recently, Borner and coworkers described an efficient Rh-deguphos catalyst for the reductive amination of a-keto acids with benzyl amine. E.e.-values up to 98% were obtained for the reaction of phenyl pyruvic acid and PhCH2COCOOH (entry 4.9), albeit with often incomplete conversion and low TOFs. Similar results were also obtained for several other a-keto acids, and also with ligands such as norphos and chiraphos. An interesting variant for the preparation of a-amino acid derivatives is the one-pot preparation of aromatic a-(N-cyclohexyla-mino) amides from the corresponding aryl iodide, cyclohexylamine under a H2/ CO atmosphere catalyzed by Pd-duphos or Pd-Trost ligands [50]. Yields and ee-values were in the order of 30-50% and 90 >99%, respectively, and a catalyst loading of around 4% was necessary. 

Not unexpectedly, alkylation of the double carbonylated complex proceeds via a base-catalysed interfacial enolization step, but it is significant that the initial double carbonylation step also involves an interfacial reaction, as it has been shown that no pyruvic acid derivatives are obtained at low stirring rates. Further evidence comes from observations of the cobalt-catalysed carbonylation of secondary benzyl halides [8], where the overall reaction is more complex than that indicated by Scheme 8.3. In addition to the expected formation of the phenylacetic and phenylpyruvic acids, the reaction with 1-bromo-l-phenylethane also produces 3-phenylpropionic acid, 2,3-diphenylbutane, ethylbenzene and styrene (Scheme 8.4). The absence of secondary carbonylation of the phenylpropionylcobalt tetracarbonyl complex is consistent with the less favourable enolization of the phenylpropionyl group, compared with the phenylacetyl group. 

Recently Benkovic and Schrayl28b and Clark and Kirby,26c have investigated the hydrolysis of dibenzylphosphoenolpyruvic acid and mono-benzylphospho-enolpyruvic acid which proceed via stepwise loss of benzyl alcohol (90%) and the concomitant formation of minor amounts (10%) of dibenzylphosphate and monobenzylphosphate, respectively. The pH-rate profiles for release of benzyl alcohol reveal that the hydrolytically reactive species must involve a protonated carboxyl group or its kinetic equivalent. In the presence of hydroxylamine the course of the reaction for the dibenzyl ester is diverted to the formation of dibenzyl phosphate (98%) and pyruvic acid oxime hydroxamate but remains unchanged for the monobenzyl ester except for production of pyruvic acid oxime hydroxamate. The latter presumably arises from phosphoenolpyruvate hydroxamate. These facts were rationalized according to scheme (44) for the dibenzyl ester, viz. 

The hydrolytic products are benzyl alcohol and the corresponding enol phosphonate produced through carboxyl group participation. In the presence of hydroxylamine the products are diverted to benzyl phenylphosphonate and pyruvate oxime hydroxamate. These experimental results contrast markedly with those observed for the phosphoacetoin system. A simple explanation for the formation of benzyl phenylphosphonic acid is generation of the penta-covalent species (47)... 

To a solution of 34.6 g of 2-(pyrrol-l-yl)benzyl alcohol in 300 ml of anhydrous tetrahydrofuran and 32 ml of tetramethylethylene diamine is added 183 ml of a 2.4 molar solution of n-butyl lithium in such a manner that the internal temperature of the reaction is maintained below 30°C. On completion of the addition, the reaction mixture is stirred at room temperature for 3 hours. The reaction mixture is then cooled to -70°C by means of a dry-ice/acetone bath, and 24 ml of ethyl pyruvate is added to the mixture over 1 minute. The reaction is then allowed to warm to room temperature and stirred overnight (18 hours). The reaction is then poured into an ice-water/ether mixture and the organic phase separated, dried over magnesium sulfate and the solvent evaporated under reduced pressure to yield ethyl-4-methyl-4H,6H-pyrrolo[l,2-a][4,l]benzoxazepine-4-carboxylate, MP 94°-96°C, which may be recrystallized from a mixture of ether-hexane (1 1). 

However, benzyl alcohols can be converted to benzaldehydes even in the dark.208 It has been reported that catalytic amounts of HBr may be used for this reaction.209 Primary aliphatic alcohols give rise to carboxylic esters. Catalytic amounts of bromine itself have been used, instead of HBr in the oxidation of lactate esters to pyruvates.210... 

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 catalytic hydrogenation of the benzoylformic acid amides of optically active amino acid esters was carried out. When the (5)-amino acid ester was used, the resulting mandelic acid had the (R)-con-figuration. When pyruvic acid amides of optically active benzylic amines were hydrogenated over palladium, optically active lactic acid was obtained in relatively high enantiomeric excess (ee 60%). The... 

The conveniently prepared pyruvated benzyl glycosides 12candl2c (Table 2) are first converted by a two-step sequences into the fluoride 47 and the TlPS-deri-vative 48, respectively. The latter are subsequently condensed, using the glyco-desilylation-protocol, to give the desired laminaritjiosides 49 in excellent yield. 

The reaction of thiazolium salt 229 with DBU in ethanol or tetrahydrofuran involved a competition yielding thiazoline 230, ylide 231, and acetaldehyde (79JA2752). Ylide 231 was also generated from the 3-benzyl-4-methyl-thiazolium salt 232 and DBU. Ylide 231 was trapped with different electrophiles. The reactions of 230 with sources of electrophilic sulfur mimic the pyruvate dehydrogenese-mediated production of enzyme-bound acetyl-dihydrolipoic acid. 

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