Pyridinium amidate (PYA) substituents impact ligand-centered hydride formation and (catalytic) hydride transfer reactivity.

Iridium complexes with pyridinium amidate (PYA) ligands reversibly bind hydrides on the PYA ligand rather than at the iridium center, thus enabling hydride storage and release akin to NAD+/NADH. To probe the factors underlying this reactivity, a series of nine operationally unsaturated iridium (III) complexes containing a O, N-bidentate phenolate PYA ligand IrCp* (ONPYA) were synthesized with different substituents either on the phenolate (H, Me, OMe, NO2) or on the PYA unit (H, CN, CONH2, NHCOMe, NH2). Crystallographic, UV-vis spectroscopic and DFT analyses indicate electronic decoupling of the pyridinium and aminophenolate units of the ligand. Upon reaction with formate, all complexes but the NH2-substituted derivative gave dihydropyridine products due to hydride storage either at the pyridinium C4 (para) or C6 (ortho) position. The ortho/para ratio was governed by the pyridinium substitution, with electron-withdrawing substituents favoring the ortho product, while the electron-donating NH2 substituent suppressed hydride formation completely. In contrast, aminophenolate substitution did not affect the regioselectivity and yielded para hydrides. The impact of aminophenolate and PYA substituents on the regioselectivity of ortho/para hydride formation was further rationalized by Löwdin population analysis. When probed in catalytic transfer hydrogenation, the complexes showed substituent-dependent activity, though remarkably little correlation with regioselectivity of the hydride formation nor with hydride stability as probed by reaction with benzoic acid. The most active complex containing an aminophenolate methyl substituent reached kobs = 7. 0 h-1. The catalytic activity trend correlates with the aminophenolate substituent effects, but not with pyridinium substitution nor HOMO-LUMO gap. These results thus disentangle distinct ligand effects, with the PYA unit governing hydride regioselectivity and stability, while the aminophenolate unit impacts the iridium electron density and catalytic activity.