Halides, alkyl, reaction with acid dianions

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). 

Carboxylic acids can be alkylated in the a position by conversion of their salts to dianions [which actually have the enolate structures RCH=C(0")2 ] by treatment with a strong base such as LDA. The use of Li as the counterion is important, because it increases the solubility of the dianionic salt. The reaction has been applied to primary alkyl, allylic, and benzylic halides, and to carboxylic acids of the form RCH2COOH and RR"CHCOOH. This method, which is an example of the alkylation of a dianion at its more nucleophilic position (see p. 458),... 

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. 

A re-investigation of the reaction between diketen and amides has shown that N-acetoacetylcarboxamides are formed most efficiently in the presence of trimethylsilyliodide. Olefins react with primary amides in the presence of mercury(ii) nitrate to give iV-substituted amides after NaBH4 reduction. The method provides a convenient procedure for the Markovnikov amidation of double bonds yields vary from 17 to 99% over 11 examples. Direct C-alkylation of secondary thioamides is achieved by the reaction of the dianion (177) with an activated halide to give (178). Esters of malonic, cyanoacetic, and /8-keto acids are readily C-amidoethylated by N-acylaziridines in the presence of triethylamine. ... 

Deprotonation and Alkylation Reactions. Reaction of the title compound with LDA and trapping of the resulting ester enolate with alkyl halides leads to mixtures of the a- and p-alkylated products (eq 1), the ratio of which can be strongly influenced by the presence or absence of Cul. Related studies have been carried out on the dianion derived from the precursor acid, and one product of such processes exploited in the synthesis of the racemic modification of the diterpene trixagol. ... 

While y-alkylations did not occur with saturated and benzylic halides, y-selectivities in the 62-99% range were observed in reactions of dicopper(I) dianions of a variety of a, -unsaturated acids with allylic halides. y-Unsubstituted allylic halides reacted by an Sn2 mechanism, y-disubstituted compounds underwent direct 5n2 displacement and y-monosubstituted systems reacted by both 5n2 and 5n2 pathways. Scheme 72 provides an example of the dramatic reversal in regioselectivity that was observed in the allylation of the dianion (147) of tiglic acid when the metal cation was changed from lithium to copper(I). The y-alkylation product from the latter species was exclusively the ( )-isomer. 

Like the reaction in Eq. 29, the selenoamide dianion 117 is generated by reacting iST-benzyl selenobenzamide with 2 equiv of BuLi (Eq. 45) [78]. Alkylation of 117 takes place selectively at the carbon atom adjacent to the nitrogen atom to the selenocarbonyl group. Alkyl halides, acid chlorides, and oxiranes are used as carbon electrophiles. Trimethylsilyl chloride performs silylation of 117, giving the selenoamide 118. 

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