Reagent-modulated optional site selectivities: The metalation of o-, m- and p-halobenzotrifluorides

Article abstract of DOI:10.1016/0040-4039(96)00415-7

Chloro(trifluoromethyl)benzenes and bromo(trifluoromethyl)benzenes undergo deprotonation at a position adjacent to the single halogen substituent when treated with alkyllithiums (at -75°C) and, respectively, lithium 2,2,6,6-tetramethylpiperidide (at -100°C) in tetrahydrofuran. Positional ambiguities, if existing, can be exploited to establish optional site selectivities. Thus, butyllithium reacts with 1-chloro-3-(trifluoromethyl)benzene under hydrogen/metal interconversion at the 2-position whereas sec-butyllithium attacks exclusively the 6-position. The latter mode of regioselectivity is also exhibited by 1-bromo-3-(trifluoromethyl)benzene in the presence of lithium 2,2,6,6-tetramethylpiperidide, only 2-bromo-4-(trifluoromethyl)phenyllithium being produced. 2-Bromo-6-(trifluoromethyl)phenyllithium is directly inaccessible, but is formed when 2-bromo-3-(trifluoromethyl)phenyllithium, generated at -100°C, is allowed to isomerize at -75°C.