Synthesis of Bempedoic Acid through Electrochemical Decarboxylation of Dialkylated Malonic Acid

Bempedoic acid is a kind of small-molecule inhibitors of adenosine triphosphate-citrate lyase (ACL) which is effective in the treatment of hypercholesterolemia and hypertension. In this paper, a new method of six-step synthesis of bempedoic acid with 42% overall yield is reported and the ketone formation by electrochemical decarboxylation of dialkylated malonic acid is introduced as the key step of this process. This method with mild conditions and high efficiency is potentially suitable for industrial production.

Ketone Formation via Decarboxylation Reactions of Fatty Acids Using Solid Hydroxide/Oxide Catalysts

A sustainable route to ketones is described where stearone is produced via ketonic decarboxylation of stearic acid mediated by solid base catalysts in yields of up to 97%, at 250 °C. A range of Mg/Al layered double hydroxide (LDH) and mixed metal oxide (MMO) solid base catalysts were prepared with Mg/Al ratios of between 2 and 6 via two synthetic routes, co-precipitation and co-hydration, with each material tested for their catalytic performance. For a given Mg/Al ratio, the LDH and MMO materials showed similar reactivity, with no correlation to the method of preparation. The presence of co-produced oxide phases in the co-hydration catalysts had negligible impact on reactivity.

Uncatalyzed CO2Li-Mediated SNAr Reaction of Unprotected Benzoic Acids via Silicon Trickery

The alkyl and aryllithium nucleophilic aromatic substitution (SNAr) displacement of a fluoro or methoxy group from unprotected 2-fluoro/methoxybenzoic acids is discussed. It was discovered that a TMS group located at the C6-position ortho to the carboxyl group shields effectively the carboxylate against nucleophilic attack, thus reducing dramatically ketone formation, and reorients nucleophilic substitution to the C2-position. The reactions with fluoro-substituted substrate 7 proceed efficiently; in contrast, the use of methoxy-functionalized benzoic acid 8 only affords moderate yields with s-BuLi and PhLi. This uncatalyzed coupling reaction, which provides a direct access to biaryl compounds, presumably proceeds by an addition–elimination sequence via intermediate formation of a resonance-stabilized pentavalent silalactone-Meisenheimer complex.

The active site accessibility aspect of montmorillonite for ketone yield in ester rearrangement

A new term Volume Accessibility Factor (VAF), the product of micropore volume and acidity, correlates with ketone formation in modified montmorillonite.