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Three Chloro(trifluoromethyl)pyridines as Model Substrates for Regioexhaustive Functionalization
Author(s) -
Cottet Fabrice,
Schlosser Manfred
Publication year - 2004
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200400066
Subject(s) - chemistry , trifluoromethyl , transmetalation , trifluoromethylation , lithium diisopropylamide , deprotonation , pyridine , steric effects , metalation , surface modification , lithium (medication) , medicinal chemistry , organic chemistry , stereochemistry , catalysis , ion , medicine , alkyl , endocrinology
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)