The direct metalation and subsequent functionalization of trifluoromethyl-substituted pyridines and quinolines

Depending on the choice of the reagent, 2-(trifluoromethyl)pyridine can be selectively metalated and subsequently carboxylated or otherwise functionalized either at the 3- or at the 6-position. "Optional site selectivity" can also be achieved with 4-(trifluoromethyl)pyridine, which may be deprotonated either at the 2- or at the 3-position. In contrast, 3-(trifluoromethyl)pyridine undergoes nucleophilic addn. and ensuing decompn. whatever the base. Depending on the reaction conditions, 2-(trifluoromethyl)quinoline displays reactivity toward lithium reagents at its 3-, 4-, or 8- positions, 3-(trifluoromethyl)quinolines at the 2- or 4-positions, and 4-(trifluoromethyl)quinoline at the 2- or 3-positions. It was therefore possible to prep. four trifluoromethyl-substituted pyridinecarboxylic acids and six trifluoromethyl-substituted quinolinecarboxylic acids regioisomerically uncontaminated and in a most straightforward way. [on SciFinder (R)]