Double Addition of Organolithium Reagents to Carboxylic Acids
Double Addition of Organolithium Reagents to Carboxylic Acids: A carboxylic acid can react with an organolithium reagent (R–Li) to form a ketone after…
What happens
A carboxylic acid can react with an organolithium reagent (R–Li) to form a ketone after acidic workup. This reaction requires 2 equivalents of R–Li: the first equivalent acts as a strong base, while the second equivalent adds a new carbon group. A new C–C bond forms, and only the second R group becomes part of the ketone.
Reaction summary
Carboxylic acid + 2 R–Li, then H₃O⁺ → ketone (new C–C bond)
Reagents and conditions
- Starting material: Cyclohexanecarboxylic acid
- Reagents: Methyllithium (CH₃Li); H₃O⁺ (acidic workup)
- Conditions: 2 equivalents of R–Li
- Products: Cyclohexyl methyl ketone (ketone)
Mechanism
- Deprotonation: The first equivalent of R–Li acts as a strong base. It removes the acidic H from the –COOH group (R′–COOH → R′–COO⁻). The R group from this first equivalent becomes R–H.
- Addition: The second equivalent of R–Li acts as a nucleophile. The carbon attached to Li attacks the carboxylate carbonyl carbon, and a dianionic intermediate is formed.
- Acidic Workup: H₃O⁺ is added. The intermediate is protonated and ultimately gives the final ketone.
Memory trick
First R–Li → BASE (removes H from –COOH). Second R–Li → NUCLEOPHILE (adds R). R–Li #1 = removes H; R–Li #2 = adds R.