Organolithium reagents reaction with carboxylic acids

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

The reactions of several carboxylic acid derivatives with organomagnesium and organolithium compounds were described in Section 14-12. The key step in these reactions is addition of the organometallic compound, as R60MS , to the carbonyl group. For a Grignard reagent,... 

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

CARBONYL ADDITIONS, CERIUM(III) CHLORIDE-PROMOTED, 76, 237 Carbonyl compounds, reactions with organolithiums or Grignard reagents, 76, 228 Carboxylic acid amides, 77, 27 Cells, storage of, 76, 80 Centrifugation, 76, 78... 

Reactions of either Grignard or organolithium reagents with most aldehydes, ketones, or esters produce alcohols. Reactions of organolithium reagents with carboxylic acids, or of Grignard reagents with nitriles, produce ketones. 

With organolithium reagents, stable intermediates are produced by addition to a carboxylic acid. On workup, these intermediates produce ketones. As with Grignard reagents, the reaction of organolithium reagents with esters produces tertiary alcohols because the intermediates decompose to ketones under the reaction conditions. The mechanisms for these processes are illustrated in the examples that follow. 

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

When chiral additives such as ( —)-sparteine has added to the initial reaction with the organolithium reagent, quenching with CO2 produces carboxylic acids with good asymmetric induction. 

Conversions of carboxylic acids to ketones are typically performed in stepwise fashion6 via intermediates such as acid chlorides,7 anhydrides,8 thioesters,9 or N-alkoxy amides,10 or by the direct reaction of carboxylic adds with lithium reagents.11 In this latter method trimethylsifyl chloride has been shown to be an effective reagent for trapping the tetrahedral alkoxide intermediates and for quenching excess organolithium reagent. 

Finally, a carboxylic acid can be converted to a ketone with an organolithium reagent. The reaction requires two moles of organolithium per mole of carboxylic acid, because one mole must react with the acid hydrogen and the second mole attacks the carbonyl group. Figure 10-15 illustrates the mechanism for this reaction. 

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