Arylpyruvic acid

The highly enantioselective reductive animation of a-keto acids as a route to amino acids is possible with ligand 118 (3 R,4R)- l-W-benzyl)-3,4-bis(diphenylphosphanyl)pyrrolidine, DEGUPHOS] and [Rh(cod)2]BF4.649 (R,R)-NORPHOS (2-exo-3-endo-bis(diphenylphosphino)bicyclo[2.2.1 ]heptene) and (2. S, 3. S ) - C HIR AP H O S (bis(diphenylphosphino)butane) are also good ligands for this transformation. Arylpyruvic acids give the best results (>95% ee). 

The Paal-Knorr reaction was also employed by Steglich in likely biomimetic approaches to the marine alkaloids lamellarin L <00CEJ1147> as well as purpurone and ningalin C <00TL9477>. The overall approach employed herein involved initial oxidative coupling of two arylpyruvic acids followed by condensation of the resulting 1,4-diketones with suitable... 

Selected examples of the conversion of benzyl chlorides into arylacetic acids and arylpyruvic acids using molybdenum carbonyl complexes ... 

Method B Co2(CO)8 (0.17 g, 0.5 mmol) and TEBA-C1 (0.23 g, 1.0 mmol) in aqueous NaOH (5M, 25 ml) and PhH (25 ml) are stirred at room temperature for 30 min under CO (1 atmos.). The benzyl halide (25 mmol) is added and the reaction mixture is stirred at room temperature for ca. 12 h. The aqueous phase is separated, washed with PhH (2 x 25 ml) and acidified to produce the arylacetic acid (with arylpyruvic acid), which is isolated using the procedure described in 8.2.2.A. The PhH solutions contain the neutral products which are formed. 

The a-keto acids are extremely versatile intermediates. For example, reduction of an arylpyruvic acid 450 yields the corresponding p-aryllactic acid 451, condensation of 450 with amines followed by reduction affords amino acid derivatives 454, ° and condensation of 450 with hydroxylamine yields a-oximi-noacids 452 as shown in Scheme 7.149. ... 

The application of arylpyruvic acids 256 in place of pyruvic acid in three-component reactions leads to dramatic changes in the direction of the process. Refluxing of starting compounds for 3 hours of irradiating with microwave at 170°C for 20 minutes in acetic acid yielded 3-hydroxy-4,5-diaryl-l-azolyl-2,5-dihydro-li/-2-pyrrolones 258 [203] (Scheme 3.73). Under ultrasonic irradiation in ethanol with the addition of catalytic amounts of hydrochloric acid or in acetic acid, the reaction proceeds in a different direction with the formation of pyrimidinecarboxylic acids 259. In the case of pyruvic acid the course of the three-component reaction does not so drastically depend on the activation method or solvent type as well as from temperature mode [202]. 

Following on from their previous work on the biomimetic synthesis of marine natural products, Steglich et al. proposed a biomimetic lamellarin synthesis in which an oxidative dimerization of an arylpyruvic acid and condensation of the resulting 1,4-dicarbonyl compound with a suitable 2-arylethylamine would be the key steps of the synthesis. Thus, the synthesis of lamellarin G trimethyl ether was achieved by coupling two molecules of 3-(3,4-dimethoxyphenyl)pyruvic acid and the appropriate 2-phenylethylamine <9579941, 97AG(E)155>. The use of a mixture of two different arylpyruvic acids afforded the unsymmetrical lamellarin L <00MI1147>. 

Oxidative decarbonylation. Arylpyruvic acids are converted to arylacetic acids using aqueous NaBOj. 

The recent isolations of sagecoumarin [35], Fig. (10) (a 3-aryloxy-6,7-dihydroxycoumarin) and 3-hydroxycoumarin [36] led us to investigate their possible obtention from conveniently substituted arylpyruvic acids. Since the dimerisation of arylpyruvic acid has been proposed in the biosynthesis of butyrolactone isolated from Aspergillus terreus [37], Fig. (11), we developed an interest in the potential acid-catalysed dimerisation of these molecules. 

In connection with our studies on the dimerisation of aylethanals and arylacetones with boron tribromide, we first turn to the reaction of methoxylated arylpyruvic acids [38], Arylpyruvic acids that were obtained mainly in their Z-enol form, did not dimerise. When the ortho aromatic position is unsubstituted, only an isomerisation occurs that allowed us to isolate some 2-hydroxyarylpropenoic acids in their E-form. In the cases of (2-methoxyphenyl)arylpropenoic acids, cyclisations were also observed leading of mixtures of benzofuran-2-carboxylic acids and 3-hydroxycoumarins that are easily separated, Fig. (12). We observed a competition between cyclisation and isomerisation that have apparently similar kinetic parameters. 

The presence of zinc amalgam is not necessary to promote the dimerisation and 2-hydroxyfuran-2-ones can also be obtained from arylpyruvic acids. The supposed mechanism of formation of these compounds involves an aldol condensation followed by a lactonisation and finally a decarboxylation [40]. 

The double carbonylation process was first found in the conversion of substituted benzyl halides to corresponding arylpyruvic acids catalyzed by cobalt carbonyl complexes in a phase transfer system (Eq. 27). ... 

Under these conditions 2-phenyl-4-(3-methoxy-4 -benzyloxybenzal)-5-oxazolone gives 3-methoxy-4-benzyloxypyruvic acid in 90% yield (ninety-six-hour reaction time) 2-phenyl-4-(3, 4 -methylenedioxyben-zal)-5-oxazolone gives the pyruvic acid in 85% yield (reaction time not given) the azlactones derived from vanillin, m-hydroxybenz deh5 de, and p-hydroxybenzaldehyde give no arylpyruvic acid. 

Procedures. 1. Conversion of Arylpyruvic Adds to the Oximes. Approximately 1 mole of the arylpyruvic acid is dissolved in 800 cc. of a solution containing 2 mole equivalents of sodium hydroxide, and 1.5 moles of hydroxykmine is added. The solution is allowed to stand for thirty-six hours, and the oxime is precipitated by acidification with dilute hyc chloric acid. The yield of oxime is 95%. 

A convenient method of converting alkyl amides into 4-alkylbutyrolactones in moderate yields has appeared. Acid-catalysed condensations between arylpyruvic acids and aromatic aldehydes give access to ketolactones of type (41) in good... 

Murlykina et al. [55] studied the three-component reaction of 5-aminopyrazoles (24), salicylic aldehydes (25) with pyruvic acid (26). The reaction involving pyruvic acid can be selectively directed to the formation of either 3-aryl-10,ll-dihydro-4,10-methanopyrazolo[4,3-c][l,5]benzoxazocine-4-carboxylic acids (27) or 3,6-diarylpyrazolo[3,4-fc] pyridine-4-carboxylic acids (28), while the reaction involving arylpyruvic acids leads only to 7-hydroxy-2,5,6-triaryl-... 

In case of arylpyruvic acids, the multicomponent reaction was found to alter the direction yielding... 

Various benzyl chlorides undergo double carbonylation on treatment with octacarbonyldicobalt under phase-transfer conditions generation of [Co(CO)4] to give arylpyruvic acids in moderate yields. "... 

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