The Enolate Chemistry of Dianions

The synthetic applications of carbanions as reagents for carbon-carbon bond formation have been highlighted numerous times throughout this text. All of the reagents covered so far have a net charge of 1 that is, they are monoanions. Are thwe others with a -2 charge (dianions), and, if so, how are they prepared, what are their properties, and how are they used in synthesis  

The pATa of acetic acid is 4.7, which corresponds to ionization of the O—H group. The pAT for ionization of a C—H bond of acetate ion is 33. None of the negative charge of the monoanion is shared by carbon. The dianion, however, has carbanionic character and the potential to act as a nucleophile in carbon-carbon bond-forming reactions. 

Diisopropylamine has a pK of 36, which makes lithium diisopropylamide (LDA) a strong enough hase to convert acetic acid to its dianion. Other carboxylic acids behave similarly to give dianions that undergo typical carhanion reactions. Alkylation of carboxylic acid dianions provide a useful altanative to the malonic este synthesis. 

Experimentally, as in this example, it is sometimes useful to convert the carboxylic acid to its carbox-ylate (monoanion) with sodium hydride (NaH, step 1) before treating with LDA (step 2). Because the dianion is a strong base, the alkyl halide used in step 3 must be methyl or primary. A pH adjustment (step 4) converts the resulting carboxylate salt to the desired carboxylic acid 

The dianions of a-halocarboxylic acids give epoxy acids (called glycidic acids) on reaction with aldehydes and ketones. 

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Descriptive Passage and Interpretive Problems 20 The Enolate Chemistry of Dianions 926... 

The photostimulated arylation of ketone enolate ions has been shown to be of fairly wide scope, although the reaction fails with the enolate ions of acetophenone and several -dicarbonyl compounds and is impeded by steric crowding. Coupled with new, mild methods for the regeneration of the carbonyl group (see Section 4), the chemistry of azomethine ketone derivatives has taken on new dimensions. The alkylation of such derivatives has been of particular interest recently. For example, two groups of workers have shown that only yn-dianions are formed on metalation of oximes. Furthermore, the dianions are configurationally stable, allowing alkylation and aldol condensation to be effected stereo-specifically (Scheme 22). - . 

Treating succinic anhydrides (64) with triethylamine, zinc chloride and trimethylchlorosilane in acetonitrile gives 2,5-bis(trimethylsiloxy)furans (65). ° The relative ease of silylation in these cases demonstrates one of the differences between enol silyl ether chemistry and classical enolate anion chemistry. It would have been quite difficult to generate the dianion of succinic anhydride. 

Looking back on the history of ketone dianion chemistry, one soon notices that dianion species, derived from / -keto esters, have been in continuous steady use in organic synthesis3,4, as shown in Scheme 2. Thus, ethyl acetoacetate can be converted to the corresponding ketone o a -chainon via consecutive proton abstraction reactions. The resulting dienolate anion reacts with a variety of alkyl halides to give products, resulting from exclusive attack at the terminal enolate anions. 

Just as the one electron reduction of a neutral molecule produces an anion radical, the one electron reduction of an organic anion can yield a dianion radical, assuming that the LUMO of the anion is not too high in energy. Two anions familiar in organic chemistry are the dibenzoylmethide (an enolate of a 6-diketone) [112] and fluorenide anions [113] (Scheme 68). 

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