Carboxylation

In general, the decarboxylation reaction is an exothermic reaction, and accordingly the carboxylation reaction seems difficult to proceed compared to decarboxylation. However, the difference in potential energy between the starting materials and products is supposed to be not so large as to totally inhibit the carboxylation reaction. In fact, Grignard reagents are well known to react with carbon dioxide at room temperature to give carboxylic acids. Of course, we are not able to utilize organometallic reagents as the carbanion equivalent in enzymatic reactions.

Figure 22: Microbial carboxylation of pyrrole.

However, if we can design some sophisticated routes to generate carbanion equivalents in the active site of the enzyme, carboxylation reaction might be possible. In fact, acetyl-CoA is carboxylated with the aid of biotin in the biosynthetic pathway of long-chain fatty acids.

As to the synthetic substrate, an unexpectedly simple compound is car-boxylated under ordinary reaction conditions. When pyrrole was incubated with Bacillus megaterium PYR2910 in the presence of carbonate and in the atmosphere of carbon dioxide, pyrrole-2-carboxylic acid was obtained in good yield (Fig. 22).88 Higher yield was achieved when the reaction was performed in supercritical carbon dioxide using intact cells of the same microorganism.89 In this case, there is a possibility that the first step of the reaction is the carboxylation of nitrogen atom as is the case of biotin-mediated carboxylation, or the canonical form by the aid of the electron-donating effect of nitrogen atom is contributed. In any event, it is revealed that a relatively mild nucleophile reacts smoothly with carbon dioxide. Accordingly, if we can design a proper substrate to generate an intermediate with some nucleophilicity, the development of new C—C bond-forming reactions is expected.

The carboxylation reaction is extremely important not only from the synthetic standpoint but also from the environmental point of view. Accordingly, studies toward this end are highly expected to develop in near future.

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