Homologation of Carboxylic Acids Using a Radical-Polar Conjunctive Reagent

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Homologation of organic molecules, adding a carbon atom, is crucial for drug discovery.
• Direct homologation of carboxylic acids, common in bioactive molecules, was previously unknown.
• Existing methods require multiple steps, derivatives, and hazardous reagents.

Purpose of the Study:

• To report the first direct, one-step homologation of native carboxylic acids.
• To introduce a novel, stable reagent for this transformation.
• To enable rapid synthesis of diverse carboxylic acid derivatives.

Main Methods:

• Utilized a novel, bench-stable (1-phosphoryl)vinyl sulfonate reagent.
• Performed a one-step homologation directly from various carboxylic acids.
• Applied the method to aliphatic building blocks and complex molecules.

Main Results:

• Successfully achieved direct one-step homologation of carboxylic acids.
• Synthesized a range of ester, amide, and carboxylic acid homologues.
• Demonstrated applicability to diverse substrates, including complex molecules.

Conclusions:

• This novel strategy provides a direct, efficient route for carboxylic acid homologation.
• The method simplifies access to diverse molecular structures for drug discovery.
• Introduced a new synthon, the distonic acylium radical, for molecular diversification.