Single‐Step Radiosynthesis of “¹⁸F‐Labeled Click Synthons” from Azide‐Functionalized Diaryliodonium Salts

Positron emission tomography (PET) is an increasingly important biomedical imaging technique that relies on the development of radiotracers labeled with positron emitters to achieve biochemical specificity. Fluorine‐18 ( t 1/2 = 109.7 min) is an attractive positron‐emitting radiolabel for organic radiotracers, primarily because of its longer half‐life and greater availability relative to those of the main alternative, carbon‐11 ( t 1/2 = 20.4 min). Rapid, simple methods are sought for labeling prospective PET radiotracers with fluorine‐18 from cyclotron‐produced aqueous [ 18 F]fluoride ion, which must often be converted first into a suitably reactive labeling synthon for use in a subsequent labeling reaction. The use of 18 F‐labeled synthons in “click chemistry” is attracting increasing attention for labeling PET radiotracers. Herein we describe rapid, single‐step radiosynthesis of azido‐ or azidomethyl‐bearing [ 18 F]fluoroarenes from the reactions of diaryliodonium salts with no‐carrier‐added [ 18 F]fluoride ion within a microfluidic apparatus to provide previously poorly accessible 18 F‐labeled click synthons in radiochemical yields of 15 % for 4‐[ 18 F]fluorophenyl azide and about 40 % for each of the [ 18 F](azidomethyl)fluorobenzenes. The radiosynthesis of the latter synthons was possible under “wet conditions”, so obviating the need to dry the cyclotron‐produced [ 18 F]fluoride ion and greatly enhancing the practicality of the method.