Ligand Oxidation Activates a Ruthenium(II) Precatalyst for C–H Hydroxylation

A new class of Ru-sulfonamidate precatalysts for sp³ C-H hydroxylation is described along with a versatile process for assembling unique heteroleptic Ru(II) complexes. The latter has enabled structure-performance studies to identify an optimal precatalyst, <b>2h</b>, bearing one 4,4'-di-<i>tert</i>-butylbipyridine (dtbpy) and one pyridylsulfonamidate ligand. Single-crystal X-ray analysis confirmed the structure and stereochemistry of this adduct. Catalytic hydroxylation reactions are conveniently performed in an aqueous, biphasic solvent mixture with 1 mol % <b>2h</b> and ceric ammonium nitrate as the terminal oxidant and deliver oxidized products in yields ranging from 37 to 90%. A comparative mechanistic investigation of <b>2h</b> against a related homoleptic precatalyst, [Ru(dtbpy)₂(MeCN)₂](OTf)₂, convincingly establishes that the former generates one or more surprisingly long-lived active species under the reaction conditions, thus accounting for the high turnover numbers. Structure-performance, kinetics, mass spectrometric, and electrochemical analyses reveal that ligand oxidation is a prerequisite for catalyst activation. Our findings sharply contrast a large body of prior art showing that ligand oxidation is detrimental to catalyst function. We expect these results to stimulate future innovations in C-H oxidation research.