Metalation and Derivatization of All Six Dichlorobenzotrifluorides:Site Selectivities

Abstract

AbstractThe metalation of 2,3‐, 2,6‐, 2,4‐ and 3,5‐dichlorobenzotrifluorides can be readily effected with standard 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, respectively. 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” mixture) 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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)