Electrochemical Flash Fluorination and Radiofluorination

Area of Science:

• Organic Chemistry
• Electrochemistry
• Radiochemistry

Background:

• Late-stage fluorination is crucial for synthesizing pharmaceuticals and agrochemicals.
• Existing methods often require harsh conditions or specialized reagents.
• Developing efficient and versatile fluorination techniques remains a key challenge.

Purpose of the Study:

• To present a novel method for rapid late-stage fluorination and radiofluorination.
• To utilize the cation pool technique combined with electrochemistry for C-F bond formation.
• To demonstrate the applicability of the method to various acetate derivatives.

Main Methods:

• Electrochemical oxidation of thioacetate precursors in 2,2,2-trifluoroethanol (TFE) at -20 °C.
• Stabilization of intermediate carbocations using a divided electrochemical cell.
• Quenching with stable-isotope [19F]fluoride or no-carrier-added radioactive [18F]fluoride for fluorination or radiofluorination.

Main Results:

• Successful rapid late-stage fluorination of methyl (phenylthio) acetate, methyl 2-(methylthio) acetate, and methyl 2-(ethylthio) acetate.
• Demonstration of both non-radioactive and no-carrier-added radioactive [18F]fluorination.
• The method provides a facile route to fluorinated and radiofluorinated compounds.

Conclusions:

• The presented electrochemical cation pool method offers a rapid and efficient approach for late-stage fluorination.
• This technique is valuable for introducing fluorine and fluorine-18 into organic molecules.
• The method holds potential for applications in drug discovery and development.