A proton-responsive annulated mesoionic carbene (MIC) scaffold on IR complex for proton/hydride shuttle: An experimental and computational investigation on reductive amination of aldehyde

Article abstract of DOI:10.1021/acs.organomet.0c00568

A Cp*Ir(III) complex (1) bearing a proton-responsive hydroxy unit on an annulated imidazo[1,2-a][1,8]naphthyridine based mesoionic carbene scaffold was synthesized by two different synthetic routes. The molecular structure of 1 revealed an anionic lactam form of the ligand. The acid?base equilibrium between the lactam-lactim tautomers on the ligand scaffold was examined by ¹H NMR and UV?vis spectra. The pK_a of the appendage ?OH group in the lactim form of 1 was estimated to assess the proton transfer property of the catalyst. The catalytic efficacy of 1 for reductive amination of aldehyde was evaluated by utilizing three different hydrogen sources: molecular H₂ⁱPrOH/KO^tBu combination, and HCOOH/Et₃N (5:2) azeotropic mixture. The HCOOH/Et₃N (5:2) azeotropic mixture rotocol was found to be the best amon the three different h dro enation methods. Catalyst 1 hydrogenates imines chemoselectively over carbonyls under the reaction conditions. A range of aldehydes was reductively aminated to the corresponding secondary amines using the HCOOH/Et₃N (5:2) azeotropic mixture. Further, catalyst 1 showed high efficiency for the reduction of a wide variety of N-heterocyclic imine derivatives. The lactam-lactim tautomerization of the ligand system is proposed for direct hydrogenation, whereas only the lactam form operates in the strongly basic medium (ⁱPrOH/KO^tBu). Under HCOOH/Et₃N (5:2) conditions, the lactam scaffold is not protonated; rather, an outer-sphere hydride transfer from formate to the Ir is proposed, which is supported by ¹H NMR and DFT calculations. Finally, ligand-promoted hydride transfer from metal-hydride to the protonated imine affords the corresponding amine. A close agreement between the experimentally estimated and computed thermodynamic/kinetic parameters gives credence to the metal-ligand cooperative mechanism for the imine hydrogenation reaction using the HCOOH/Et₃N (5:2) azeotropic mixture.