Recommendable Routes to Trifluoromethyl-Substituted Pyridine- and Quinolinecarboxylic Acids

• Published in: European journal of organic chemistry Vol. 2003; no. 8; pp. 1559 - 1568
• Main Authors: Cottet, Fabrice, Marull, Marc, Lefebvre, Olivier, Schlosser, Manfred
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.04.2003; WILEY‐VCH Verlag; Wiley
• Subjects: Building blocks; Carboxylation; Chemistry; Chemistry, Organic; Heterocycles; Organometallic intermediates; Physical Sciences; Science & Technology; Sulfur tetrafluoride; Trifluoromethylcopper; ORTHO-LITHIATION; HALIDES; REDUCTIVE DEHALOGENATION; MAGNESIUM EXCHANGE-REACTION; CYANATION; PYRIDINES; sulfur tetrafluoride; trifluoromethylcopper; organometallic intermediates; heterocycles; ORGANIC FLUORINE-COMPOUNDS; carboxylation; building blocks
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200390215

As part of a case study, rational strategies for the preparation of all ten 2‐, 3‐, or 4‐pyridinecarboxylic acids and all nine 2‐, 3‐, 4‐, or 8‐quinolinecarboxylic acids bearing trifluoromethyl substituents at the 2‐, 3‐, or 4‐position were elaborated. The trifluoromethyl group, if not already present in the precursor, was introduced either by the deoxygenative fluorination of suitable carboxylic acids with sulfur tetrafluoride or by the displacement of ring‐bound bromine or iodine by trifluoromethylcopper generated in situ. The carboxy function was produced by treatment of organolithium or organomagnesium intermediates, products of halogen/metal or hydrogen/metal permutation, with carbon dioxide. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)