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, 2h, bearing one 4,4′-di-tert-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 % 2h and ceric ammonium nitrate as the terminal oxidant and deliver oxidized products in yields ranging from 37 to 90%. A comparative mechanistic investigation of 2h 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.