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

Chloro(trifluoromethyl)benzenes and bromo(trifluoromethyl)benzenes undergo deproronation at a position adjacent to the single halogen substituent when treated with alkyllithiums (at -75 degrees C) and respectively, lithium 2,2,6,6-tetramethylpiperidide (at -100 degrees C) in tetrahydrofuran. Positional ambiguities, if existing, on 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-(tiinuoromethyl)phenyllithium is directly inaccessible, but is formed when 2-bromo-3-(trifluoromethyl)phenyllithium, generated at -100 degrees C, is allowed to isomerize at -75 degrees C. Copyright (C) 1996 Elsevier Science Ltd.