Three chloro(trifluoromethyl)pyridines as model substrates for regioexhaustive functionalization

As a further test of the concept of regioexhaustive functionalization, 2-chloro-6-(trifluoromethyl)pyridine, 2-chloro5-(trifluoromethyl)pyridine and 3-chloro-4-(trifluoromethyl)pyridine were each converted into the three possible carboxylicacids-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. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).