Preparation of ortho-Fluorophenols from Non-Aromatic Precursors: Mechanistic Considerations for Adaptation to Fluorine-18 Radiolabeling

摘要

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 ortho-fluorophenols regioselectively, 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.