Direct decarboxylative ¹⁸F-fluorination of benzoic acids using visible light catalysis

Area of Science:

• Organic Chemistry
• Radiochemistry
• Photochemistry

Background:

• ¹⁸F-labeled compounds are crucial for Positron Emission Tomography (PET) imaging.
• Direct C-H functionalization methods for ¹⁸F-fluorination are highly sought after.
• Existing methods often require harsh conditions or complex precursors.

Purpose of the Study:

• To develop a mild and direct method for the decarboxylative ¹⁸F-fluorination of (hetero)aromatic carboxylic acids.
• To utilize a photoinduced ligand-to-metal charge transfer (LMCT) process for this transformation.
• To demonstrate the broad applicability and efficiency of the developed method.

Main Methods:

• Direct decarboxylative ¹⁸F-fluorination using a photoinduced LMCT process.
• Utilizing visible light photoredox catalysis.
• Optimization of reaction conditions for various (hetero)aromatic carboxylic acids.

Main Results:

• Successful ¹⁸F-labeling of diverse benzoic acids with radiochemical conversions (RCC) ranging from 16% to 40%.
• Demonstrated the preparation of 1-fluoro-4-[¹⁸F]fluorobenzene in a full batch with an overall radiochemical yield (RCY) of 27 ± 2%.
• The method operates under mild conditions, avoiding harsh reagents or high temperatures.

Conclusions:

• The developed photoinduced LMCT method offers a mild and efficient route for direct ¹⁸F-fluorination.
• This approach expands the toolkit for synthesizing ¹⁸F-labeled radiotracers.
• The method shows promise for broader applications in medicinal chemistry and PET imaging development.