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.

Iron-catalyzed formation of 2-aminopyridines from diynes and cyanamides.

Diynes and cyanamides undergo an iron-catalyzed [2 + 2 + 2] cycloaddition to form highly substituted 2-aminopyridines in an atom-efficient manner that is both high yielding and regioselective. This system was also used to cyclize two terminal alkynes and a cyanamide to afford a 2,4,6-trisubstituted pyridine product regioselectively.

The iron-catalyzed construction of 2-aminopyrimidines from alkynenitriles and cyanamides.

Several cycloaddition catalysts and reagents were surveyed for their effectiveness toward cyclizing alkynenitriles with cyanamides. Catalytic amounts of FeI2, (iPr)PDAI and Zn were found to effectively catalyze the [2+2+2] cycloaddition of a variety of cyanamides and alkynenitriles to afford bicyclic 2-aminopyrimidines.

Iron-catalyzed cycloaddition of alkynenitriles and alkynes.

The combination of Fe(OAc)(2) and an electron-donating, sterically hindered pyridyl bisimine ligand catalyzes the cycloaddition of alkynenitriles and alkynes. A variety of substituted pyridines were obtained in good yields.