Organometallics carboxylation with carbon

Carboxylic acid groups can also be installed in molecules using the reaction of an organometallic compound with carbon dioxide. This is a reductive method since the carbon dioxide is reduced to a carboxylic acid by formation of a new carbon-carbon bond. Both Grignard reagents and organolithium compounds work well in this reaction. 

For carboxylations with carbon dioxide reversed-order addition is generally carried out, i.e. the solution or suspension of the metallated compound is poured on the powdered dry ice , which may be covered with an organic solvent. The reason for applying this technique is that alkali salts of carboxylic acids can undergo an attack by the organometallic derivative ... 

We already know a number of routes to carboxylic acids, and this section will add an important new one, the reaction of organometallic reagents with carbon dioxide. 

The aryl bromides undergo facile metalation with butyl lithium to produce aryllithium derivatives with the expected organometallic activity.9 For example, reaction of lithiated PPO with carbon dioxide produces a carboxylated PPO which exhibits unique blending characteristics18. 

A The alkynyl hydrogen of propyne is acidic and hence the propyne will form an organometallic derivative. The Grignard derivative will react with carbon dioxide to give the carboxylic acid. Cis alkenes are formed by the catalytic hydrogenation of alkynes using a Lindlar catalyst. Hence a propynyl alcohol is a precursor to compound (b). This could be obtained by the addition of a propyne anion to propanone ... 

The secondary reduction of the terminal radical by Sml2 generates samarium alkyl species which are suitable for classical organometallic reactions, e.g. protonation, acylation, reactions with carbon dioxide, disulfides, diselenides, or the Eschenmoser salt. A broad variety of products is available (hydroxy-substituted alkanes, esters, carboxylic acids, thioethers, selenoethers, tertiary amines) by use of the double-redox four-step (reduction-radical reaction-reduction-anion reaction) route (Scheme 20) [73]. 

Kosugi, Y., Rahim, M. A., Takahashi, K., Imaoka, Y., Kitayama, M. Carboxylation of alkali metal phenoxide with carbon dioxide at ambient temperature. Applied Organometallic Chemistry 2000,14, 841-843. 

The use of thienyl Grignard reagents, and more recently lithiated thiophenes, has been extensive and can be illustrated by citing formation of oxythiophenes, either by reaction of the former with f-butyl perbenzoate or the latter directly with bis(trimethylsilyl) peroxide or via the boronic acid, the synthesis of thiophene carboxylic acids by reaction of the organometallic with carbon dioxide, the synthesis of ketones, by reaction with a nitrile, or alcohols by reaction with aldehydes, by the reaction of 2-lithiothiophene with A -tosylaziridine, and by syntheses of thieno[3,2- ]thiophene and of dithieno[3,2- 2, 3 - /]thiophene. Some of these are illustrated below. 

Ethyl pyridine-2-acetate and ethyl 6-methylpyridine-2-acetate have previously been prepared by carboxylation of the lithio derivatives of a-picoline and lutidine, respectively. Use of ethyl carbonate to acylate the organometallic derivative avoids the intermediacy of the (unstable) carboxylic acid, and the yields are better. In the present procedure potassium amide is used as the metalating agent the submitters report that the same esters may be formed by metalation with sodium amide (43% yield) or with w-butyllithium (39% yield). The latter conditions also yield an appreciable amount of the acid (which decarboxylates). 

The reaction of carbon nucleophiles derived from organometallics with carboxylic acid derivatives follows closely the reactions we have already encountered in Sections 6.3.2 and 7.6.2. Organometallics... 

Thienothiophenes 1 and 2 with ethylmagnesium bromide afford organometallic derivatives that can be carbonated to form the 2-carboxylic acids identical with those prepared by oxidation of the 2-acetyl derivatives.19-21,26,218 Thieno[3,2-i]thiophene-2,5-dicarboxylic acid was obtained analogously in the reaction of thienothiophene 2, using an excess of ethylmagnesium bromide.218... 

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