Regioselective functionalization of pyridines using a directed metalation or a halogen/metal exchange

Abstract

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. © 2013 Verlag der Zeitschrift für Naturforschung, Tübingen.