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Malonic Ester Synthesis: History
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Chemistry, Organic
Contributor: Helena Kang

Within advanced synthetic organic chemistry, malonic ester synthesis is a carbon-chain construction sequence that converts a malonic diester into a substituted acetic acid by modifying the activated methylene carbon and then removing one carboxyl group. The concept is bounded by three necessary operations: generation of a resonance-stabilized enolate from the doubly activated methylene, carbon–carbon bond formation with an electrophilic partner, and hydrolytic decarboxylation that leaves a monoacid. Diethyl malonate and related malonic diesters supply two electron-withdrawing carbonyl groups that render the methylene hydrogens sufficiently acidic for deprotonation, thereby defining the nucleophilic intermediate of the alkylation or conjugate-addition step [1]. Conceptual limits exclude enolate alkylations that do not start from a malonic diester and do not terminate in decarboxylation to an acetic-acid framework. The sequence is distinguished from acetoacetic-ester synthesis by the diester rather than β-keto ester activating group and by the acetic-acid rather than methyl-ketone product. Related C–C bond constructions that retain the malonate motif include metal-catalyzed arylation of diethyl malonate and base-promoted 1,4-addition of diethyl malonate to allenic ketones, both of which still rely on the same activated methylene as the nucleophilic site [2].

  • malonic ester
  • enolate alkylation
  • decarboxylation
  • substituted acetic acid

Advanced Synthetic Organic Chemistry • Organic Chemistry • Chemistry • Physical Sciences

References

  1. Edward J. Hennessy; Stephen L. Buchwald; A General and Mild Copper-Catalyzed Arylation of Diethyl Malonate. Org. Lett. 2002, 4, 269-272, 10.1021/ol017038g.
  2. Shengming Ma; Shichao Yu; Shaohu Yin; Studies on K2CO3-Catalyzed 1,4-Addition of 1,2-Allenic Ketones with Diethyl Malonate: Controlled Selective Synthesis of β,γ-Unsaturated Enones and α-Pyrones. J. Org. Chem. 2003, 68, 8996-9002, 10.1021/jo034633i.
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