Selective Amination of Trihalopyridines

Significance

Chemoselective C-halogen to C-N bond formation for 5-bromo-2-chloro-3-fluoro­pyridine as a function of conditions is reported. For cross-coupling conditions A, the reaction is, as expected on the basis of halogen reactivity, exclusively bromo-chemoselective to give secondary and tertiary aminopyridines in high yields. For S_NAr conditions B, using primary amines, preference for C3 over C2 substitution is observed. The elimination of HF to form a pyridyne appears not to be involved in view of the absence of a 4-aminopyridine adduct and the exclusive regioselectivity. For conditions C, the normal behavior of nucleophilic reactivity of C2 >> C3 is observed.