Esters dioxo

Scheme 2.2.7.1 The expected regio- and enantioselective reduction of 3,5-dioxo esters A.

Scientists at Bristol-Myers Squibb, after screening various microorganisms, selected a bacterial strain of Acinetobacter calcoaceticus SC 13876 to reduce a 3,5-dioxo ester 20 to the dihydroxy ester 21 (Scheme 19.13).103 The diol 21 is a key intermediate in the synthesis of an HMG-CoA reductase inhibitor (22). In a 1-L batch reaction, a yield of 92% was obtained with an optical purity... 

L J. Szarka, Stereoselective microbial or enzymatic reduction of 3,5-dioxo esters to 3-hy-droxy-5-oxo, 3-oxo-5-hydroxy, and 3,5-dihydroxy esters, E. R. Squibb Sons, Inc., EP 0569998A2 1993. 

The lithium enolate of AUV-dimethylacetamide underwent addition to 2-aryl-1-nitroethenes to give /faryl-y-nitroamides. The lithium dianions and the trianions of /l-oxo esters and /i,y-dioxo esters undergo addition to 2-aryl-1-nitroethenes to give bicyclic compounds as a single dia-stereomer8. 

Unsaturatcd carboxylic acids arc selectively hydroxylated on the double bonds. Pentafluoro-prop-1-enyl)malonate is selectively dihydroxylated by potassium permanganate on the fluorinated carbons. The intermediate geminal fluorohydrins 3 immediately eliminate hydrogen fluoride to give dioxo esters, such as 4, as the final product (vide supra).90... 

A few years later, a new process for the (R)-HPB ester was reported by Solvias in collaboration with Ciba SC (see Figure 2.11). Claisen condensation of cheap acetophenone and diethyl oxalate was carried out, followed by chemo- and enantioselective hydrogenation of the resulting diketo ester and hydrogenolysis to the HPB ester [30]. Even though the 2,4-dioxo ester was a new substrate type, it took only a few months to develop, scale up, and implement the new process. The following aspects were the key to success (i) the low price of the diketo ester prepared via Claisen... 

In 30 mL of EtOAc, ca. 20 mL of 2-methylpropene, and 10.0 g (69 mmol) of methyl 2,4-dioxopentanoate are internally irradiated by means of a 100-W high-pressure mercury lamp at —50 to — 60 °C under N2 for 37 h. Chromatography of" the mixture (silica gel, hexane/EtOAc 9 1) gives the dioxo ester (obtained by photoaddition followed by a retro-Michael reaction) as a colorless oil yield 6.7 g (56%). The title compound was used further in a synthesis of deoxytrispolone. 

Reactive groups present in a molecule may also have a decisive influence on ether fission vinyl ethers and enol ethers of 1,3-diketones or of 1,3-dioxo esters are as sensitive to acids as are glycosides and ethers of ketones, e.g. 2-hydroxycyclohexanone, are also surprisingly easily attacked.11... 

A few of the many possible condensations are that of two molecules of an ester to give a / -oxo ester, of an ester with a ketone to give a 1,3-diketone, of a formic ester with a ketone to give a 3-oxo aldehyde, of an oxalic ester with a ketone to give a dioxo ester, and of an alkyl carbonate with a nitrile to give an oc-cyano carboxylic ester. 

The methodology has been extended to C-C coupling reactions of alkenes and S-dicarbonyl compounds with air as the oxidant and with CeCl3 7H20 as the catalyst (Christoffers et al., 2003b Rdssle et al., 2005). The reactions yield diastereoisomeric mixtures of hydroxyperox-ides, which disproportionate in presence of acetyl chloride/pyridine by Kornblum-DeLaMare fragmentation into dioxo esters (scheme 62). These dioxo derivatives have a 1,4-dicarbonyl structural motif. This reaction has been explored with styrene and substituted alkenes as the alkene substrate. 

Stetter and his co-workers have extended their investigations of the thiazolium salt-catalysed condensation of aldehydes with activated olefins cf. 1, 191) to include a synthesis of dioxo-esters (Scheme 31) ° Although yields are not always... 

H-Cyclopenta[7,8]naphtho[2,3-6]furan-7-yl glyoxylate, 2,3,6,10-tetrahydro-6-hydroxy-6-methyl-3,10-dioxo-, methyl ester H NMR. 4, 560 (66JCS(C)743) Cyclopenta[6]quinoline, 6,7,8,9-tetrahydro- C NMR, 2, 122 (77JOC300, 77JOC2742)... 

Glutamic acid, p-aminobenzoyl-2-amino-8-methyl-4,9-dioxo-6,7,8,9-tetrahydro-4H-pyrazino[l,2-u][l,3,5]tria2in-7-ylmethyl ester, 3, 308... 

This derivative is prepared from an A-protected amino acid and the anthrylmethyl alcohol in the presence of DCC/hydroxybenzotriazole. It can also be prepared from 2-(bromomethyl)-9,10-anthraquinone (Cs2C03). It is stable to moderately acidic conditions (e.g., CF3COOH, 20°, 1 h HBr/HOAc, / 2 = 65 h HCl/ CH2CI2, 20°, 1 h). Cleavage is effected by reduction of the quinone to the hy-droquinone i in the latter, electron release from the —OH group of the hydroqui-none results in facile cleavage of the methylene-carboxylate bond. The related 2-phenyl-2-(9,10-dioxo)anthrylmethyl ester has also been prepared, but is cleaved by electrolysis (—0.9 V, DMF, 0.1 M LiC104, 80% yield). ... 

The related 2-phenyl-2-(9,10-dioxo)anthrylmethyl ester has also been prepared, but is cleaved by electrolysis (—0.9 V, DMF, 0.1 MLiC104, 80% yield). ... 

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