Theoretical Study on Iridium-Catalyzed Hydrogenolysis of Urea: Mechanistic Insights into Metal–Ligand Cooperation and the Origin of Chemoselectivity

Achieving chemoselective hydrogenolysis of carbonyl compounds that defies the well-known electrophilicity order remains challenging yet promising for upgrading nitrogen-containing waste. Herein, we present density functional theory (DFT) calculations to elucidate the unclear mechanism of the highly chemoselective hydrogenolysis of urea to amide catalyzed by an Ir complex. Results show that the metal–ligand cooperative isocyanate pathway is more favorable than a conventional hemiaminal pathway, where the pyrrolyl moiety in the ligand serves as a proton transfer station by assisting N–H bond cleavage of urea. The unusual chemoselectivity favoring urea over amide counters carbonyl electrophilicity, arising from the fact that the isocyanate pathway is kinetically unfavorable for amide due to the endothermic generation of H2 as a byproduct. Interestingly, the Cs[IrIII(NP)(H)2(OtBu)(urea)]− ate complex generated in situ with CsOtBu exhibits superior proton transfer capability that effectively lowers the energy barrier of the isocyanate pathway. Consequently, Ir-catalyzed hydrogenolysis of carbamate is achieved, whereas it cannot succeed without CsOtBu. Furthermore, a positive correlation between the N–H bond dissociation energy of the substrate and the energy barrier was disclosed. These results provide fundamental insight into carbonyl hydrogenolysis reactivity and a strategy for precise conversion under mild conditions.