Three Chloro(trifluoromethyl)pyridines as Model Substrates for Regioexhaustive Functionalization

Abstract As a further test of the concept of regioexhaustive functionalization, 2‐chloro‐6‐(trifluoromethyl)pyridine, 2‐chloro‐5‐(trifluoromethyl)pyridine and 3‐chloro‐4‐(trifluoromethyl)pyridine were each converted into the three possible carboxylic acids 2, 4, 6, 8 , 10, 12 , 16, 17 and 20 . This was achieved by employing several, but not all of the organometallic “toolbox methods”: transformation of a more basic organometallic species into a less basic isomer by transmetalation‐equilibration, site discriminating deprotonation with lithium N , N ‐diisopropylamide or lithium 2,2,6,6‐tetramethylpiperidide, regio‐divergent iodine migration and steric screening of acidic positions by a bulky trialkylsilyl group. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)