Practical Routes to 2,6-Disubstituted Pyridine Derivatives

We report the synthesis of a series of 2,6‐disubstitutedpyridines in a straightforward manner starting from readily available 2‐substituted pyridines. The main sequence involves a selective α‐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.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) A series of 2,6‐disubstituted pyridines was prepared starting from readily available 2‐substituted pyridines. The main sequence involves a selective reaction with halogen functionalization followed by a Grignardreaction catalyzed by Fe(acac)3. Pyridines bearing an aryl moiety in the 6‐position and an alkyl chain, including highly fluorinated groups, in the 2‐position were obtained.