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

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.