Fluorine- and Trifluoromethyl-Substituted Toluenes: Site Selective Metalation of Aromatic or Benzylic Positions

If employed in tetrahydrofuran and at -75 °C, the superbasic mixture of butyllithium and potassium tert-butoxide metalates 2-, 3- and 4-fluorotoluene exclusively at an aromatic position adjacent to the halogen, as demonstrated by quenching with carbon dioxide to give the corresponding benzoic acids. In contrast, a mixture of lithium diisopropylamide and potassium tert-butoxide selectively deprotonates the benzylic positions of 2- and 3-fluorotoluene to give after quenching with carbon dioxide the corresponding phenylacetic acids. With 3-(trifluoromethyl)-toluene, metal/hydrogen exchange again occurs at the methyl group while the corresponding 2- and 4-isomers do not produce interceptable organometallic intermediates.