(Radio)fluoroclick Reaction Enabled by a Hydrogen-Bonding Cluster

Area of Science:

• Organic Chemistry
• Radiochemistry
• Medicinal Chemistry

Background:

• Radiolabeling with fluorine-18 (¹⁸F) is crucial for Positron Emission Tomography (PET) imaging.
• Developing efficient and robust methods for incorporating ¹⁸F into organic molecules remains a significant challenge.

Purpose of the Study:

• To develop a novel and widely applicable nucleophilic radiofluorination reaction.
• To enable the efficient incorporation of ¹⁸F into ynamide-containing molecules.

Main Methods:

• Development of a nucleophilic (radio)fluoroclick reaction utilizing ynamides.
• Employing readily available and easy-to-handle potassium fluoride (KF) as the fluoride source.
• ¹⁸F radiolabeling under ambient atmosphere conditions.

Main Results:

• The reaction demonstrated high functional group tolerance.
• Extraordinarily high radiochemical yields were achieved for the ¹⁸F addition to C-C unsaturated bonds.
• The developed method is applicable to a wide range of ynamides.

Conclusions:

• A versatile and efficient method for nucleophilic radiofluorination of ynamides has been established.
• This reaction provides a valuable tool for the synthesis of ¹⁸F-labeled compounds for PET imaging.
• The reaction's operational simplicity and high yields facilitate broader application in radiopharmaceutical development.