Flow electrochemistry: a safe tool for fluorine chemistry

Area of Science:

• Organic Chemistry
• Electrochemistry
• Medicinal Chemistry

Background:

• Fluorine-containing compounds are crucial in pharmaceuticals, driving demand for advanced fluorination methods.
• Existing fluorination procedures often face challenges in scalability, safety, and efficiency.

Purpose of the Study:

• To develop a scalable, versatile, and safe electrochemical fluorination protocol.
• To enable efficient synthesis of fluorinated compounds using hypervalent iodine chemistry in flow.

Main Methods:

• Anodic oxidation of an iodoarene mediator to generate transient (difluoroiodo)arenes.
• Electrolysis in the absence of other reagents for facile isolation of iodine(iii) difluorides.
• Coupling electrolysis with downstream reactions in a continuous flow system.

Main Results:

• Achieved high yields in a broad range of hypervalent iodine mediated reactions.
• Demonstrated high productivity (up to 834 mg h⁻¹) with reduced reaction times using high flow rates.
• Successfully integrated the process into an automated system with in-line quenching for enhanced safety.

Conclusions:

• The developed electrochemical flow fluorination protocol offers a safe, scalable, and efficient alternative to traditional methods.
• Continuous generation and immediate use of unstable (difluoroiodo)arenes in flow mitigate toxicity and instability issues.
• This method significantly advances the synthesis of valuable fluorinated compounds for pharmaceutical development.