Bench-Top Radical Fluorination Platform for Fast, Selective C–F Bond Formation

Background:

Fluorination is critical for pharmaceuticals, agrochemicals, and advanced materials, as C–F bonds improve bioavailability, stability, and metabolic resistance. However, conventional fluorination methods often require harsh reagents, high temperatures, or expensive catalysts that limit scope and selectivity. Radical fluorination offers a promising alternative but lacks practical, controllable fluorine sources that can operate under mild, scalable, and safe conditions.

Technology Overview:

This invention employs silver(II) fluoride (AgF₂) dissolved in acetonitrile to generate electrophilic fluorine radicals at room temperature. The solvent coordinates with AgF₂, lowering activation energy for radical formation and enhancing chemoselectivity. The platform enables direct C–H and decarboxylative fluorination of alkanes, alkenes, carboxylic acids, and heterocycles—achieved without additional catalysts, bases, or specialized fluorinating reagents. Mechanistic validation through DFT modeling and radical-trapping experiments confirms the radical pathway. Reactions proceed under UV or visible light, offering broad substrate tolerance and compatibility with late-stage fluorination workflows.

Advantages:

• Operates at room temperature with a single, commercially available reagent
• Eliminates need for metal catalysts, bases, or hazardous F₂/XeF₂ reagents
• Enables late-stage C–H and decarboxylative fluorination with high selectivity
• Compatible with diverse organic scaffolds, including heterocycles and aliphatic compounds
• Safer and more controllable than conventional fluorination routes
• Simplifies discovery chemistry by reducing steps and reaction setup complexity
• Potential for adaptation to ¹⁸F radiolabeling for PET imaging applications

Applications:

• Late-stage fluorination in drug discovery and medicinal chemistry
• Decarboxylative fluorination of fatty acids and complex intermediates
• Dearomative and heterocyclic fluorination for new material and bioactive compound synthesis
• Production of fluorinated agrochemicals with enhanced stability and efficacy
• ¹⁸F radiolabeling platform for PET tracer development

Intellectual Property Summary:

• US Provisional Application 63/808,065 – Filed May 19, 2025

Stage of Development:

Lab-scale validation – Demonstrated selective C–F bond formation across multiple substrate classes under ambient conditions using UV and visible light. TRL ~3–4.

Licensing Status:

This technology is available for licensing.

Licensing Potential:

Highly relevant to pharmaceutical, materials, and agrochemical industries seeking scalable, safe, and cost-effective late-stage fluorination methods for drug discovery, process chemistry, and labeled compound synthesis.

Additional Information:

Reaction data, mechanistic DFT analysis, and substrate scope results available upon request.