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

Chloro(trifluoromethyl)benzenes and bromo(trifluoromethyl)benzenes underwent deprotonation at a postion adjacent to the single halogen substituent when treated with alkyllithiums (at -75 DegC) and, resp., lithium 2,2,6,6-tetramethylpiperidide (at -100 DegC) in THF. Positional ambiguities, if existing, were be exploited to establish optional site selectivities. Thus, the reaction of butyllithium with 1-chloro-3-(trifluoromethyl)benzene led to hydrogen/metal interconversion at the 2-position whereas the reaction of sec-butyllithium led exclusively to a reaction at the 6-position. The latter mode of regioselectivity was also exhibited by 1-bromo-3-(trifluoromethyl)benzene in the presence of lithium 2,2,6,6-tetrmethylpiperidide, and only 2-bromo-4-(trifluoromethyl)phenyllithium was produced. 2-Bromo-6-(trifluoromethyl)phenyllithium was directly inaccessible, but was formed when 2-bromo-3-(trifluoromethyl)phenyllithium, (generated at -100 DegC) was allowed to isomerize at -75 DegC. [on SciFinder (R)]