Preparation of o-Fluorophenols from Nonaromatic Precursors: Mechanistic Considerations for Adaptation to Fluorine-18 Radiolabeling

The preparation of fluorine-18 labeled o-fluorophenols at high specific activity is challenging and requires use of [¹⁸F]fluoride ion as the radioisotope source. As a novel, alternative approach, we found that treatment of α-diazocyclohexenones with Selectfluor and Et₃N·3HF followed by HF elimination and tautomerization afforded o-fluorophenols regioselectively and rapidly. To adapt this chemistry to ¹⁸F radiolabeling, using bromine electrophiles in place of Selectfluor gave the o-fluorophenol via an α-bromo-α-fluoroketone intermediate in lower but still reasonable yields.