Reactions at the Carbonyl Group—Oxidation and Reduction

Methods of synthesis for carboxylic acids include (1) oxidation of alkyl-benzenes, (2) oxidative cleavage of alkenes, (3) oxidation of primary alcohols or aldehydes, (4) hydrolysis of nitriles, and (5) reaction of Grignard reagents with CO2 (carboxylation). General reactions of carboxylic acids include (1) loss of the acidic proton, (2) nucleophilic acyl substitution at the carbonyl group, (3) substitution on the a carbon, and (4) reduction. 

Acyl substituents at the 3- and/or 4-positions result in decreased hydrolytic stability compared with the alkyl and aryl derivatives described above. Despite this constraint most of the usual reactions of the carbonyl group are possible. Aldehydes <9ILA1211> and ketones are oxidized to the carboxylic acid, borohydride reduction affords the expected alcohols, and epoxides are formed on reaction with diazomethane. Oximes and arylhydrazones are formed with hydroxylamine and arylhydrazines, and the products may subsequently undergo monocyclic rearrangement involving the oxadiazole to give the corresponding isomeric furazans and 1,2,3-triazoles (Section 4.05.5.1.4). 

Oxidation and reduction reactions occur at the carbonyl group of monosaccharides, so they all begin with the monosaccharide drawn in the acyclic form. We will confine our discussion to aldoses as starting materials. 

Step (2) Reduction of the Carbonyl Group The acetoacetyl-ACP formed in the condensation step now undergoes reduction of the carbonyl group at C-3 to form d-j8-hydroxybutyryl-ACP. This reaction is catalyzed by /3-ketoacyl-ACP reductase (KR) and the electron donor is NADPH. Notice that the D-j3-hydroxybutyryl group does not have the same stereoisomeric form as the l-j8-hydroxyacyl intermediate in fatty acid oxidation (see Fig. 17-8). 

The Diels-Alder reaction of 3-methoxyfuran with octyl vinyl ketone took place at room temperature in quantitative yield to afford exclusively the endo cycloadduct (27) (81CC221). Reduction of the carbonyl group with lithium tri-r-butoxyaluminum hydride produced a single alcohol (28). Ozonolysis of the double bond followed by Jones oxidation yielded the lactone ester (29). Hydrolysis of the ester and lead tetraacetate oxidation gave the lactone acetate. This was converted by further hydrolysis and Jones oxidation to the bis-lactone (30), a known intermediate in the synthesis of ( )-isoavenaciolide (Scheme 6). 

Reactions at the a-carbon atom are affected by the presence of 02. First, by rapidly removing the reducing species, it blocks reductive deamination. This is thought to explain the protective effect of 02 on alanine destruction 26). Secondly, 02 also probably alters the mechanism of oxidative deamination though the products (NH3 and the carbonyl group) are the same 39). 

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