Dianions carboxylic acid

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

Table 110 Complexes of Tertiary or-Hydroxy Carboxylic Acid Dianions...

Fig. 13.10. Formation of carboxylate enolates ("carboxylic acid dianions") by reaction of carboxylic acid salts with strong bases.

Carboxylic acid dianions may be readily alkylated at the more reactive a-site to produce a-alkylated acids upon acidic work-up (equation 69)504,505. This reaction has been reviewed by Petragnani and Yonashiro506. The reaction is commonly followed by decarboxylation, which yields a ketone. 

Carboxylic acid dianions have also been alkylated by reaction with aziridines to give novel y-amino substituted acids in good yields508. Methoxybenzoic acids have also been alkylated in a reductive process by reaction with lithium in ammonia followed by treatment with an alkyl halide. The product formed in this one-pot reaction is an alkylated cyclohexa-2,5-diene carboxylic acid507. 

Unsymmetrically substituted succinic acid derivatives can be prepared by reaction of carboxylic acid dianions with lithium a-iodocarboxylates (40-70% yield). 

Scheme 13 Diastereomeric transition states for carboxylic acid dianion 2,3-rearrangement of a steroidal 17-ethylidene-16a ether...

Although electrophilic amination of carboxylic acid dianions is potentially a very short route to a-amino acids and their derivatives, little work has been published and yields achieved so far, with few exceptions (Eq. 107),407 are low. Animations of the dianions of a, 3-unsaturated acids are discussed in the section on o.,fj-unsaturated carbonyl compounds (see below). 

A.V. The Noyori Open-Chain Model. In the Mukaiyama reaction, the Zimmerman-Traxler and Evans models are not satisfactory for predicting diastereoselectivity. Several open (nonchelated) transition states have been considered as useful models. The condensation reaction of carboxylic acid dianions with aldehydes indicated that anti selectivity increased with increasing dissociation of the gegenion (the cation, M+),224 When analyzing an aldol condensation that does not possess the bridging cation required for the Zimmerman-Traxler model, an aldehyde and enolate adapt an eclipsed orientation as they approach. Noyori reported syn selectivity for the reaction of a mixture of (Z)-silyl enol ether 389 and ( )-silyl enol ether 390 with benzaldehyde in the presence of the cationic tris-(diethylamino) sulfonium (TAS).225 xhis reaction is clearly a variation of the Mukaiyama reaction, which does not usually proceed with good diastereoselectivity... 

A third route to rra 5-2,3-dibenzylbutyrolactones involves oxidative dimerisation of the dianion of a dihydrocirmamic acid (scheme 7) [51,52]. Reduction of the anhydride to the lactone completes the sequence. This approach, which is ideally suited to the preparation of symmetrically substituted lignans, has also been extended to the preparation of unsymmetrically substituted compounds [53]. This is achieved by reacting an a-iodocarboxylate anion with an appropriate carboxamide dianion or carboxylic acid dianion. 

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

A completely different approach to Y-keto-esters proceeds via Michael additions of carboxylic acid dianions to an a-anilino-acrylonitrile followed by alkylation of the resulting anion and finally acidic hydrolysis (Scheme 13). Overall yields are in the range 47-79% the method is also useful in the synthesis of r-keto-amides. An alternative anion-based route to y-keto-esters utilizes the homoenolate (166) as the interroediate which undergoes smooth acylation by a wide variety of acid chlorides.The homoenolate is obtained from the corresponding iodoester using Zn-Cu couple, and it seems likely that the method can be used to prepare more highly substituted keto-esters although such reactions have not yet been reported. 

Syntheses via carboxylic acid dianions and trimethylsilyl esters of ) -ketocarboxylic acids and ketones... 

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