Pyruvic acid asymmetric hydrogenation

Knoop and Martius102a) reported the asymmetric hydrogenation of the Schiff base obtained from (S)-arginine and pyruvic acid as early as 1939. 

The use of proline methyl ester as a chiral auxiliary in the asymmetric synthesis of alanine is shown on the following page. The idea is to start with 2-oxopropanoic acid (pyruvic acid), which has the correct carbon skeleton, and replace tire oxygen on carbon 2 with an amino group and a hydrogen. This must be done in such a manner as to produce only the S-enantiomer of the amino acid, that is, L-alanine. This is accomplished by first attaching a chiral auxiliary, the methyl ester of L-proline, to the acid. In the critical step of the process, the catalytic hydrogenation, the chirality of the... 

The temperature effect could be explained by the chelation mechanism. - The Schiff s base composed of a-keto acid and optically active amine interacted with the catalyst to form a substrate-catalyst complex (14) at lower temperature at higher temperatures, the population of the unchelated structure (15) would increase as shown in Scheme 6. Asymmetric hydrogenation involving () )-a-phenylglycinate and ethyl pyruvate has also been studied. ... 

Bartok, M., Balazsik, K., Szollosi, G., Bartok, M. (2001) Solvent and support effects in the case of acetic acid and alumina Oxonium cations in asymmetric hydrogenation of ethyl pyruvate over dihydrocinchonidine modified platinum, Catal. Commun. 2,269-272. 

At almost the same time, MacMillan and coworkers found that the reductive amination starting from aldehyde, amine, and Hantzsch ester 39 also proceeded smoothly by means of 1 in the presence of 5 A MS to afford benzylic amines 43 with 83-97% ee (Scheme 11.11) [22]. They proved that dialkyl ketones as well as alkyl aryl ketones were suitable substrates even methyl ethyl ketone was reduc-tively aminated with 83% ee. They also reported the asymmetric reduction of pyruvic-acid-derived cyclic imino ester 44. In this reaction, the structure of 44 exhibited a remarkable correlation to MM3 calculations in terms of both hydrogen bond orientation and specific architectural elements that dictate iminium enan-tiofacial discrimination. 

The enantioselective hydrogenation of prochiral substances bearing an activated group, such as an ester, an acid or an amide, is often an important step in the industrial synthesis of fine and pharmaceutical products. In addition to the hydrogenation of /5-ketoesters into optically pure products with Raney nickel modified by tartaric acid [117], the asymmetric reduction of a-ketoesters on heterogeneous platinum catalysts modified by cinchona alkaloids (cinchonidine and cinchonine) was reported for the first time by Orito and coworkers [118-121]. Asymmetric catalysis on solid surfaces remains a very important research area for a better mechanistic understanding of the interaction between the substrate, the modifier and the catalyst [122-125], although excellent results in terms of enantiomeric excesses (up to 97%) have been obtained in the reduction of ethyl pyruvate under optimum reaction conditions with these Pt/cinchona systems [126-128],... 

Studies on the transamination reaction between f-butyl esters of optically active amino acids and methyl pyruvate were carried out, as shown in Scheme 7. The resulting iminodicarboxylic acid (16) was partially hydrolyzed and then oxidized with f-butyl hypochlorite to form alanine. The oxidation is a generally applicable one, and the optical purity of alanine is high (50-70%). Similar asymmetric transamination between an (S)-amino acid and ketones was carried out. Catalytic hydrogenation of the Schiff s bases prepared from a-keto acid esters and amino acid esters was carried out, and a substituent and temperature effect observed (de 40-70%). ... 

Asymmetric catalytic hydrogenation of the Schiff base prepared from ethyl pyruvate and an optically active amine in different solvents was carried out and supports the chelation hypothesis. Figure 1 shows solvent effects in the synthesis of alanine and a-aminobutyric acid( ). When (g.)-benzylic cimine was used as the asymmetric moiety, the optical purity of the resulting cotiino acid increased with a decrease in solvent polarity(, 2) A temperature effect was also observed, and the optical purity of the cimino acids increased upon lowering the reaction temperature(, , 10). ... 

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