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)]
Cite this item
Schlosser, M., & Marull, M. (2003). The direct metalation and subsequent functionalization of trifluoromethyl-substituted pyridines and quinolines. European Journal of Organic Chemistry, (8), 1569–1575. https://doi.org/10.1002/ejoc.200390216
Click Copy to copy the citation, or select the text manually.
WOS:000182357500024
2003
8
1569
1575
CAN 139:214306 27-17 Heterocyclic Compounds (One Hetero Atom) Inst. de Chim. Mol. et Biol.,Ecole Politech. Federale,Lausanne,Switz. Journal 1434-193X written in English. 588702-61-8P Role: BYP (Byproduct), SPN (Synthetic preparation), PREP (Preparation) (direct regioselective metalation and subsequent functionalization of trifluoromethyl-substituted pyridines and quinolines); 347-42-2 (2-(Trifluoromethyl)quinoline); 368-48-9 (2-(Trifluoromethyl)pyridine); 3796-23-4 (3-(Trifluoromethyl)pyridine); 3796-24-5 (4-(Trifluoromethyl)pyridine); 25199-76-2 (3-(Trifluoromethyl)quinoline); 25199-77-3 (4-(Trifluoromethyl)quinoline) Role: RCT (Reactant), RACT (Reactant or reagent) (direct regioselective metalation and subsequent functionalization of trifluoromethyl-substituted pyridines and quinolines); 131747-41-6P; 231291-22-8P (2-(Trifluoromethyl)-5-pyridinecarboxylic acid); 326894-74-0P; 625115-02-8P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (direct regioselective metalation and subsequent functionalization of trifluoromethyl-substituted pyridines and quinolines); 18706-39-3P; 87407-12-3P; 131747-42-7P; 131747-43-8P; 136483-17-5P; 155377-05-2P; 155495-82-2P; 158063-66-2P; 221313-10-6P; 587886-26-8P; 588702-60-7P; 588702-62-9P; 588702-63-0P; 588702-64-1P; 588702-65-2P; 588702-67-4P; 588702-68-5P; 588702-69-6P Role: SPN (Synthetic preparation), PREP (Preparation) (direct regioselective metalation and subsequent functionalization of trifluoromethyl-substituted pyridines and quinolines)
REVIEWED
EPFL