Aluminum amalgam keto esters

Metal amalgams may be used for reduction of the keto groups in keto esters provided the medium does not cause hydrolysis of the ester. Because of that aluminum amalgam in ether is preferable to sodium amalgam in aqueous solutions. Diethyl oxalacetate was reduced to diethyl malate by sodium amalgam in 50% yield and with aluminum amalgam in 80% yield [148], Stereospecific reduction of a- and fi-keto esters to optically pure hydroxy esters was achieved by biochemical reduction in moderate to good yields. Saccharomyces cerevisiae converted methyl 2-keto-2-phenylacetate to methyl... 

Reduction of oximino esters, i.e. oximes of keto esters, is very useful for the preparation of amino esters. Reductions are very selective since the oximes are easily reduced by catalytic hydrogenation over 10% palladium on carbon in ethanol (yield 78-82%) I094, by aluminum amalgam in ether (yields 52-87%) [750, 70P5], or by zinc dust in acetic acid (yield 77-78%). None of these reagents attacks the ester group. The last mentioned reaction gives an N-acetyl derivative [1096. ... 

Compound (1) and its enantiomer provide a variation on the same theme of stereospecific reductive amination. In this case, reduction of a chiral cyclic hydrazone (derived from an a-keto acid and (1)) with Aluminum Amalgam in wet DME proceeds with high stereoselectivity. Reductive cleavage of the N-N bond and ester hydrolysis complete the procedure, which produces a-amino acids with high optical purity (eq 4). The source of chirality is recovered by conversion of the resulting indoline-2-methanol back into (1). ... 

In contrast, the latter. ryw-isomer, ethyl (TS,2R)-2-(1 -hydroxymethyl)-4-pentenoate. was recently prepared as the only product of a reduction with an enzyme fraction obtained from baker s yeast176. Introduction of a sulfur-containing functional group into the substrate increases stereocontrol in baker s yeast reduction of many ketonesI2e>. 2-Methylthio-3-keto esters are selectively reduced to the (3S)-3-hydroxy esters (Table 5)123,127. The 2-methylthio group is easily removed by 3-chloroperbenzoic acid oxidation to the corresponding sulfoxide followed by subsequent reduction with aluminum-mercury amalgam. Thus, these compounds can also be used for the preparation of optically pure 2-unsubstituted 3-hydroxy esters. 

Corey and Chaykovsky described the reduction of carboxylic esters to ketones by way of / -keto sulfoxides. The ester is treated in tetrahydrofuran with a solution of methylsulfinyl carbanions in a mixture of dimethyl sulfoxide and tetrahydrofuran at 0°. This yields a j8-keto sulfoxide which is reduced with aluminum amalgam in 90% aqueous tetrahydrofuran.527 The methylsulfinyl carbanions are formed by the action of sodium hydride on dimethyl sulfoxide under nitrogen at 65-70°. 

Reduction of the a-keto ester of an optically active alcohol, followed by hydrolysis of the a-hydroxy ester which results, yields an optically active a-hydroxy acid. Sixty years ago, for example, McKenzie (1904) reduced optically active (—)-menthyl phenyl-glyoxylate with aluminum amalgam in moist ether and obtained unequal amounts of diastereomeric (—)-menthyl mandelates. Saponification, however, gave racemic mandelic acid. Later work (McKenzie and Humphries, 1909) showed that racemization could be avoided by acetylation of the intermediate mandelate before saponification, and that reduction of (—)-menthyl phenylgly-oxylate produced mandelic acid having an excess of the R- —) enantiomer [Eq. (5)]. 

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