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Z. Naturforsch. 2013,
68b, 411 – 422
doi:10.5560/ZNB.2013-3061
Regioselective Functionalization of Pyridines using a Directed Metalation or a Halogen/Metal Exchange
Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5–13, 81377 München, Germany
Reprint requests to Prof. Dr. Paul Knochel. Fax: +49-(0)89-2180-77680. E-mail:
Paul.Knochel@cup.uni-muenchen.de
Received February 19, 2013 / published online Juli 2, 2013
Dedicated to Professor Heinrich Nöth on the occasion of his 85th birthday
This review describes the various ways of functionalizing the pyridine scaffold using either directed metalation or halogen/metal exchange. Deprotonation can be accomplished with different lithium amides or alkyllithium reagents at low temperature. Milder conditions and higher functional group tolerance can be achieved by using ate-bases with different metals (Cd, Mg, Zn) or TMP (2,2,6,6-tetramethylpiperidyl) metal reagents (metal = Mg, Zn, Zr). With alkyllithium reagents it is also possible, by carefully adjusting the reaction conditions, to perform bromine/lithium exchange reactions. Organomagnesium reagents, like iPrMgX (X = Br, Cl·LiCl), may be used for exchanging more sensitive iodinated or brominated pyridines.
Key words: Pyridines, C-H Activation, Halogen/Metal Exchange