Chemoselective Hydrogenolysis of Formamides in the Presence of Esters by an Iridium Catalyst

Catalytic hydrogenation and hydrogenolysis using molecular hydrogen have recently attracted attention because of their high atom efficiencies, and their application to the chemoselective reduction of amides in the presence of esters has been actively explored. However, reports on the selective hydrogenolysis of amides via C−N bond cleavage are limited. In this study, the Ir-catalyzed chemoselective hydrogenolysis of formamides is achieved in the presence of esters. Specifically, this reaction enables the selective hydrogenolysis of formamides bearing a variety of substituents in the presence of esters while also achieving formamide-selective hydrogenolysis in substrates possessing both ester and formamide functional groups. A catalytic cycle is proposed involving metal−ligand−alkaline metal cooperation. Hammett analysis reveals that electron-withdrawing groups accelerate the reaction, supporting hydride transfer from the Ir center to the carbonyl carbon as the rate-determining step in the proposed cycle. Additionally, density functional theory calculations indicate that differences in the stabilization energies of substrate coordination to the lithium cation preferentially favor formamide complexation and reduction, thereby accounting for the observed chemoselectivity. Therefore, this study provides a catalysis design using a transition-metal and an alkaline metal for achieving chemoselective hydrogenolysis of amides in the presence of esters.