The functionalization of pyridines and related heterocycles is very important because of their biological properties and relevance to material science. The benzylic arylation of pyridines, in particular, is a challenging synthetic problem. Palladium-catalyzed arylations of 2-picoline involving direct C—H activation have no generality, and only few examples have been reported. Thus, azaarenes bearing electron-withdrawing groups may be arylated at 100 °C with a Pd catalyst. Several alternative procedures involving the fragmentation of a 2-(2-pyridyl)ethanol, the arylation of N-oxides, and N-iminopyridinium ylideshave been described. These methods, although displaying generality, require modified N-heterocyclic precursors.In addition, whereas 2-picoline (1a) can be functionalized in this way, the arylation of 4-picoline (2 a) has not been described. The difficulty in forming a new carbon-carbon bond with metalated 2-picoline (3; or 4-picoline) may be due to the nature of the palladium complexes (4a-c) resulting from the reaction with ArPdX (Scheme 1). We anticipate that all of these possible structures are reluctant to undergo a reductive elimination because of the chelation of the heterocyclic nitrogen with the Pd center. Hartwig and co-workers have already shown that palladium-catalyzed aminations are accelerated by a Lewis acid (BEt3). Nolan and co-workers haye also reported that reductive eliminations of Pd complexes are accelerated by AlCl3.
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