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

Abstract

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 pKa 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 H2, iPrOH/KOtBu combination, and HCOOH/Et3N (5:2) azeotropic mixture. The HCOOH/Et3N (5:2) azeotropic mixture protocol was found to be the best among the three different hydrogenation 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/KOtBu). 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.