Ethyl 3-oxobutanoate, conversion

Ethyl 4-phenyl-2-oxobutanoate oxime, which is easily prepared as a single E isomer, was hydrogenated with a neutral (R,S)-DPAMPP/Ir complex and (n-C4H9)4NI under 48 atm of H2 to afford the S amino ester in 93% ee, whereas the conversion was low (Scheme 5) [13]. 

Nitropyrimidinone 3 is also confirmed to be a suitable substrate for RTF reaction. When pyrimidinone 3 is allowed to react with diethyl 3-oxo-pentanedioate 19b in the presence of triethylamine, the RTF reaction effectively proceeds to afford 3,5-bis(ethoxycarbonyl)-4-pyridone 21b (Scheme 11). The C2 - N1 - C6 moiety of pyridone 21b is derived from 3, which means that nitropyrimidinone 3 behaves as the synthetic equivalent of activated di-formylamine 5. While 2,4,6-heptanetrione 19d causes the RTF reaction under the same conditions, giving 21d, ethyl 3-oxobutanoate requires conversion to sodium enolate 13a for preparation of 21a, due to the presence of only a single active methylene group [40]. 

While in the presence of 2-oxoglutaric acid neither decarboxylation nor acyloin condensation had been observed, as expected from previously published results (75), we succeeded in the enzymatic conversion of the mono ethyl ester 3 to ethyl 4-oxobutanoate 4, using both whole yeast cells (Saccharomyces cerevisiae) and purified PDC. The oxo ester 4 served as substrate for a second reaction catalyzed by PDC. Formation of a new carbon-carbon bond was accomplished in the presence of pyruvic acid which acted as donor of a C2-unit. Thus, ethyl 4-hydroxy-5-oxohexanoate 5 was obtained for the first time as the result of an enzymatic acyloin condensation. Finally, traces of acid induced the lactonization of hydroxyester 5, indicating it as direct precursor of solerone 1 (Figure 1). 

Marine microalgae have also been used for the stereoselective reduction of a- and P-keto esters to the corresponding hydroxy esters [30]. The marine algae were photoautotrophically cultivated in synthetic seawater at 20 °C under constant aeration and illumination by white fluorescent light. In particular, Nannochloropsis sp. catalyzed the reduction of ethyl 2-methyl-3-oxobutanoate 20 to the anti-hydroxy ester (2S,3S)-20b with high conversion, excellent diastereoselectivity syn/anti = 1 99), and high enantioselectivity (anti >99%, syn 98%) (Scheme 12.14). 

The same group has also reported a similar study for the stereocontroDed reduction of a- and (3-keto esters with micro green algae CMorella strains [31]. Ethyl 2-methyl-3-oxobutanoate 20 was reduced almost quantitatively (98% conversion) to the corresponding sy -(2R,3S)-hydroxy ester 20a, with high diaster-eoselectivity (syn/anti = >99/99% ee) in the presence of glycerol (Scheme 12.14). 

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