Iron-Catalyzed Amide Formation from the Dehydrogenative Coupling of Alcohols and Secondary Amines

The five-coordinate iron(II) hydride complex ((PNP)-P-iPr)Fe(H)(CO) ((PNP)-P-iPr = N[CH2CH2((PPr2)-Pr-i)](2)) selectively catalyzes the dehydrogenative intermolecular coupling of alcohols and secondary amines to form tertiary amides. This is the most productive base-metal catalyst for dehydrogenative amidation reported to date, in some cases achieving up to 600 turnovers. The catalyst works well for sterically undemanding amines and alcohols or cyclic substrates and is particularly effective in the synthesis of formamides from methanol. However, the catalyst performance declines rapidly with the incorporation of large substituents on the amine or alcohol substrate. Variable-temperature NMR spectroscopic studies suggest that the catalyst resting state is an off-cycle iron(II) methoxide species, ((PN)-P-iPr(H)P)Fe(H)(OCH3)(CO), resulting from addition of methanol across the Fe-N bond of ((PNP)-P-iPr)Fe(H)(CO). This reversibly formed iron(II) methoxide complex is favored at mild temperatures but eliminates methanol upon heating.