Electrophilic reactions carboxylic acid dianions

G. Reactions of Carboxylic Acid Dianions with Electrophiles. 503... 

B.vii. Acid Dianions. All of the named reactions discussed in Section 9.4 constitute relatively minor variations of the fundamental condensation reaction of aldehydes, ketones, or acid derivatives with another aldehyde, ketone, or acid derivative. The ability to produce kinetic enolates from acid derivatives has made possible another useful modification of the enolate reaction. Carboxylic acids have an acidic proton that is removed by 1 equivalent of base to first give a carboxylate (see 226). Addition of a second equivalent of a powerful base such as a dialkylamide leads to the dianion (227). Subsequent reaction with an electrophilic species, in this case 1-bromobutane, occurred first at the more nucleophilic a-carbon to give hexanoic acid. 2 The carboxylate is usually generated with n-butyllithium and the enolate with LDA, although 2 equivalents of LDA can be used. As discussed in Chapter 8, treatment of a carboxylic acid with an excess of an organo-... 

The dianions derived from furan- and thiophene-carboxylic acids by deprotonation with LDA have been reacted with various electrophiles (Scheme 64). The oxygen dianions reacted efficiently with aldehydes and ketones but not so efficiently with alkyl halides or epoxides. The sulfur dianions reacted with allyl bromide, a reaction which failed in the case of the dianions derived from furancarboxylic acids, and are therefore judged to be the softer nucleophiles (81JCS(Pl)1125,80TL505l). 

Organoytterbium chemistry has been developed in the last 20 years, although the development rate is much slower than the other lanthanides like samarium or cerium. Dianionic complexes that are produced from the reaction of ytterbium with diaryl ketones react with various kinds of electrophiles including carbon-heteroatom unsaturated bonds.35 Phenylytterbium iodide, a Grignard-type reagent, is known to have reactivity toward carbon dioxide,36 aldehydes, ketones,37,37 and carboxylic acid derivatives38,3811 to form the corresponding adducts respectively. 

Self-condensation of the dianion of cyclopropanecarboxylic acid (450) at 50 °C affords the electrophilic cyclopropane (451). Reaction of the dianion with other carboxylate salts. 

V. Conclusions - The preceding discussion should convince the reader that metalatedcarboxylic acids have substantial versatility in organic synthesis on both small and large scales. The literature cited suggests that much more attention has been devoted to the examination of reactions with various electrophiles than to the properties and methods of formation of the dianions upon which particular applications depend for success. It is likely that the future will provide the methodology necessary for the metalation of difficult carboxylic acids, such as, acetic and cyclopropane carboxylic acids, and insight into the structures of the... 

As expected, reaction of the dimetallated acids with one equivalent of electrophilic reagents occurs specifically on the strongly basic C-centre. With acetic acid we obtained poor results in alkylation reactions (compare Refs. [9] and [10]), presumably due to the slight solubility of the dianions . Carboxylic acids with a longer carbon chain give the alkylation products in good yields [10]. 

Knight explored the C2-lithiation of indole-3-carboxylic acids [326, 327]. Similar to the reaction with alcohol 100, two equivalents of LDA were used to generate dianion intermediates which upon quenching with electrophiles gave 2-(substituted)indole-3-carboxylic acids. This strategy was later used by Fisher... 

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