Practical routes to 2,6-disubstituted pyridine derivatives

We report the synthesis of a series of 2,6-disubstituted pyridines in a straightforward manner starting from readily available 2-substituted pyridines. The main sequence involves a selective alpha-lithiation reaction with halogen functionalization followed by a Grignard reaction catalyzed by Fe-(acac)(3). After demonstration of the easy feasibility of this strategy by synthesizing 2,6-disubstituted pyridines 1, the route was applied to obtain pyridine derivatives bearing electron-donating or electron-withdrawing groups. Thus, a series of pyridines bearing an aryl moiety in the 6-position and an alkyl chain in the 2-position was obtained. The pyridines were studied for their self-assembly abilities at the interface between an organic solution and the basal plane of graphite. Preliminary STM results for one compound are reported. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).