Open AccessPreparation of o-Fluorophenols from Nonaromatic Precursors: Mechanistic Considerations for Adaptation to Fluorine-18 Radiolabeling
Author(s) -
Norio Yasui,
Christopher G. Mayne,
John A. Katzenellenbogen
Publication year - 2015
Publication title -
organic letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.94
H-Index - 239
eISSN - 1523-7060
pISSN - 1523-7052
DOI - 10.1021/acs.orglett.5b02640
Subject(s) - selectfluor , chemistry , fluorine , electrophile , bromine , fluoride , tautomer , halogenation , combinatorial chemistry , organic chemistry , electrophilic fluorination , reagent , inorganic chemistry , catalysis
The preparation of fluorine-18 labeled o-fluorophenols at high specific activity is challenging and requires use of [(18)F]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 (18)F 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.