Organolithium reagents from carboxylic acids

M. S. Jorgenson, "Preparation of Ketones from the Reaction of Organolithium Reagents with Carboxylic Acids, Organic Reactions 18, 1 (1970). 

M. J. Jorgenson, Preparation of ketones from the reaction of organolithium reagents with carboxylic acids, Org. React. 1970,18, 1-9. 

Preparation of ketones from the reaction of organolithium reagents with carboxylic acids... 

FIGURE 19.28 Ketones from organolithium reagents and carboxylic acids. 

Organolithium reagents can be used to synthesize ketones from carboxylic acids. Organolithiums are so reactive toward carbonyls that they attack the lithium salts of carboxylate anions to give dianions. Protonation of the dianion forms the hydrate of a ketone, which quickly loses water to give the ketone (see Section 18-13). 

Alcohols, aldehydes, ketones and carboxylic acids can be prepared from Grignard reagents. ArMgBr, and organolithium compounds, ArLi. by reaction with molecules with an electron-delicieni site. 

On a small scale, it is convenient to add the carboxylic acid to two equivalents of LDA10 or other lithium amide, but larger experiments can be performed by addition of an available organolithium reagent to a suspension of a preformed salt containing equivalent or lesser molar amounts of the amine.12,13 Diisopropylamine reacts more rapidly than carboxylate salts with n-butyllithium. When LDA so formed abstracts a proton from the carboxylate-salt, the amine produced can react again with addi-... 

Note The organolithium reagent C cannot be made directly from B because the presence of the carboxyl group in B would lead to intermolecular destruction of the reagent by an acid-base reaction. In practice, B is first converted to its sodium salt by treatment with sodium hydride, NaH, and then the organolithium reagent is prepared.)... 

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