Regioselective Iron-Catalyzed [2 + 2 + 2] Cycloaddition Reaction Forming 4,6-Disubstituted 2‑Aminopyridines from Terminal Alkynes and Cyanamides

Iron complexes bound by redox-active
pyridine dialdimine (PDAI) ligands catalyze the cycloaddition of two
terminal alkynes and one cyanamide. The reaction is both chemo- and
regioselective, as only 4,6-disubstituted 2-aminopyridine products
are formed in moderate to high yields. Isolation of an iron azametallacycle
(4) suggests that catalyst deactivation occurs with a
large excess of cyanamide over longer reaction times. Fe-catalyzed
cycloaddition allowed for a straightforward synthesis of a variety
of aminopyridines, including known estrogen receptor ligands.