15.34 : Alkylation of β-Diester Enolates: Malonic Ester Synthesis

Malonic ester synthesis is a method to obtain α substituted carboxylic acids from ꞵ-diesters such as diethyl malonate and alkyl halides.

The reaction proceeds via abstraction of the acidic α hydrogen from a ꞵ-diester to produce a doubly stabilized enolate ion. The nucleophilic enolate attacks the alkyl halide in an S_N2 manner to form an alkylated malonic ester intermediate with a new C–C bond. Further treating the intermediate with aqueous acid or base results in the hydrolysis of the two ester groups to give a 1,3-dicarboxylic acid. The resulting ꞵ-diacidis unstable at high temperatures and readily eliminates CO₂ through a cyclic six-membered transition state, forming an enol. The enol tautomerizes to its more stable keto form producing a monosubstituted carboxylic acid. However, a disubstituted carboxylic acid is achieved if the deprotonation and alkylation steps are repeated before hydrolysis and decarboxylation.