Base-Catalyzed Aryl Halide Isomerization Enables the 4-Selective Substitution of 3-Bromopyridines

The base-catalyzed isomerization of simple aryl halides is presented and utilized to achieve the 4-selective etherification, hydroxylation and amination of 3bromopyridines. Mechanistic studies support isomerization of 3-bromopyridines to 4-bromopyridines proceeds via pyridyne intermediates and that 4-substitution selectivity is driven by a facile SNAr reaction. Beneficial aspects of a tandem aryl halide isomerization/selective interception approach to aromatic functionalization are demonstrated.