Examination of the mechanism of the intramolecular amination of N-(3-bromopyridin-2-yl)azaheteroarylamines and N-(2-chloropyridin-3-yl)azaheteroarylamines: a Pd-catalyzed amination and/or a base-assisted nucleophilic aromatic substitution?

Article abstract of DOI:10.1016/j.tet.2007.02.041

The intramolecular amination of N-(3-bromopyridin-2-yl)azaheteroarylamines and N-(2-chloropyridin-3-yl)azaheteroarylamines was investigated. In this way we unraveled the mechanism of the ring closure reaction in the auto-tandem amination (inter- and intramolecular Pd-catalyzed amination) of 2,3-dibromopyridine with amino(benzo)(di)azines and 2-chloro-3-iodopyridine with amino(benzo)(di)azines, respectively. Depending on the substrate a Pd-catalyzed amination, a base-assisted nucleophilic aromatic substitution or?a combination of both is occurring. An explanation based on the aromaticity of the amidine, supported by theoretical calculations, is provided. In addition we gained evidence that the intramolecular metal-catalyzed amination of N-(3-bromopyridin-2-yl)azaheteroarylamines and N-(2-chloropyridin-3-yl)azaheteroarylamines indeed involves a nitrogen atom that is not substituted with a hydrogen atom.