90731-83-2Relevant articles and documents
Regioselective Arylation of 3-Bromopyridine
Comins, Daniel L.,Mantlo, Nathan B.
, p. 1239 - 1243 (2007/10/02)
The addition of aryl Grignard reagents to the 1-phenoxycarbonyl salt of 3-bromopyridine affords 2-aryl-5-bromo-1-phenoxycarbonyl-1,2-dihydropyridines and 4-aryl-3-bromo-1-phenoxycarbonyl-1,4-dihydropyridines.The crude dihydropyridines were aromatized with o-chloranil in refluxing toluene to give 4- and 6-aryl-3-bromopyridines.The regioselectivity of this two-step process, 6- vs. 4-substitution, was examined and found to be dependent upon the structure of the Grignard reagent.Unhindered aryl Grignard reagents, e.g., phenyl and 2-naphthyl, gave mainly 6-aryl-3-bromopyridines (49-52percent) along with 9percent of the 4-substituted isomer and less than 4percent of the 2-aryl-3-bromopyridine.Hindered aryl Grignard reagents, e.g., o-tolyl and 1-naphthyl, are less regioselective.When a catalytic amount of cuprous iodide is present during the Grignard reaction, nearly exclusive 1,4-addition results.The crude 4-aryl-3-bromo-1,4-dihydropyridines were aromatized with p-chloranil to provide 4-aryl-3-bromopyridines in good yield and high isomeric purity.The sequential use of the cuprous iodide-catalyzed Grignard reaction and the "normal" Grignard reaction provided a regiospecific synthesis of 3-bromo-6-(p-methoxyphenyl)-4-phenylpyridine from 3-bromopyridine.
