Malonic Acid : A Carbonyl Dianion Synthon

Diketones, ketoesters and polyketones are privileged building blocks for the construction of a wide range of useful carbo- and hetero-cyclic compounds. For example, 1,4-diketones are extensively used as synthetic precursors for the assembly of a variety of biologically active compounds.

In view of the widespread occurrence of these key-functional groups in numerous important products and their use as basic synthons for the construction of a wide variety of carbo- and hetero-cyclic structures, it is little surprising that many methods have been developed to access these valuable synthetic intermediates. Among them, the conjugate addition of acyl equivalents to Michael acceptors is likely the most popular route to the construction of 1,4-diketones. 

We have recently identified malonic acids derivatives as precursors of acetals and ketones.

Electrosynthesis of MOM Ethers

The protection of functional groups plays an important role in organic synthesis, especially in the synthesis of complex molecules such as natural products. Among the plethora of protecting groups available to protect hydroxyl groups, methoxymethyl (MOM) ethers have proven to be a popular choice to protect alcohols and phenols due to their high tolerance toward a wide range of reaction conditions. Nevertheless, the toxicity of MOM-Cl remains a serious problem.

We have recently developed a novel electrochemical methodology for preparing MOM ethers under safe, inexpensive and scalable conditions.

“Electrochemical methoxymethylation of alcohols-a new, green and safe approach for the preparation of MOM ethers and other acetals ” Luo X., Ma X., Lebreux F., Markó I.E., Lam K., Chem. Commun., 2018, 54, 9969.

Electrochemical Activation of Benzoic Acids

The study of the electrochemical and chemical behavior of electrochemically generated benzoyloxy radicals will be undertaken through this project. Literature reports very few ways to generate these radicals. For instance, the main ones are the thermal decomposition of the unstable benzoyl peroxide  and the CuCl-catalyzed decomposition of copper benzoate.  As a result, benzoyloxy radicals have been rarely used as a chemical reagent but most of the time as a radical-chain initiator.

Generation of benzoyloxy radicals by electrolysis of the corresponding carboxylate would be an appreciable alternative since neither metal or potentially explosive materials like peroxides, will be used in the process.

Even though aromatic carboxylates have been reported to not undergo Kolbe reaction,  electrolysis of benzoic acid, in presence of an excess of aliphatic acid, leads cleanly to the formation of the ester which presumably results from a recombination between a benzoyloxy radical and a radical formed by the Kolbe decarboxylation of an aliphatic acid.  Such a process would allow the formation of esters under very mild conditions. In fact, the reaction could be performed in basic, neutral or slightly acidic medium. Therefore, such conditions would be suitable for compounds that are usually unstable or easily epimerized under acidic conditions. Another interesting application would be the electrolysis in presence of pivaloic acid. This should give an easy way to form t-butyl esters that are usually difficult to prepare under standard chemical conditions.

"Electrochemical Synthesis of Phthalides via Anodic Activation of Aromatic Carboxylic Acids" Hayrapetyan D., Viacheslav Shkepu V., Seilkhanovc O. T., Zhanabil Z. Lam K., Chem. Commun., 2017, 10.1039/C7CC03669H