Metalation and derivatization of all six dichlorobenzotrifluorides: Site selectivities

The metalation of 2,3-, 2,6-, 2,4- and 3,5-dichlorobenzotrifluorides can be readily effected with std. reagents such as lithium diisopropylamide, lithium 2,2,6,6-tetramethylpiperidide, and butyllithium at the chlorine-adjacent 4- and 3-positions and the chlorine-flanked 3- and 4-positions, resp. However, regioselectivity was secured with 2,6-dichlorobenzotrifluoride only under equilibrating conditions as the initial deprotonation occurs simultaneously at the 3- and 4-positions. 3,4-Dichlorobenzotrifluoride requires methyllithium in the presence of potassium tert-butoxide ("LIM-KOR" mixt.) to undergo regioselective metalation at the 2-position. All the organometallic intermediates were converted into the corresponding benzoic acids by trapping with carbon dioxide, arguably the most popular electrophile for the characterization of organometallic intermediates. [on SciFinder (R)]