Ligand Oxidation Activates\na Ruthenium(II) Precatalyst\nfor C–H Hydroxylation

A new class of Ru-sulfonamidate precatalysts for sp<sup>3</sup> C–H hydroxylation is described along with a versatile\nprocess\nfor assembling unique heteroleptic Ru(II) complexes. The latter has\nenabled structure–performance studies to identify an optimal\nprecatalyst, <b>2h</b>, bearing one 4,4′-di-<i>tert</i>-butylbipyridine (dtbpy) and one pyridylsulfonamidate ligand. Single-crystal\nX-ray analysis confirmed the structure and stereochemistry of this\nadduct. Catalytic hydroxylation reactions are conveniently performed\nin an aqueous, biphasic solvent mixture with 1 mol % <b>2h</b> and ceric ammonium nitrate as the terminal oxidant and deliver oxidized\nproducts in yields ranging from 37 to 90%. A comparative mechanistic\ninvestigation of <b>2h</b> against a related homoleptic precatalyst,\n[Ru(dtbpy)<sub>2</sub>(MeCN)<sub>2</sub>](OTf)<sub>2</sub>, convincingly\nestablishes that the former generates one or more surprisingly long-lived\nactive species under the reaction conditions, thus accounting for\nthe high turnover numbers. Structure–performance, kinetics,\nmass spectrometric, and electrochemical analyses reveal that ligand\noxidation is a prerequisite for catalyst activation. Our findings\nsharply contrast a large body of prior art showing that ligand oxidation\nis detrimental to catalyst function. We expect these results to stimulate\nfuture innovations in C–H oxidation research.