Nondirected Palladium-Catalyzed C(sp3)–H Oxygenation with H2O2

Abstract Palladium(II) complexes of the TPA family (TPA = tris(2-pyridylmethyl)amine) catalyze selective C(sp3)–H oxyfunctionalizations but have so far been unable to activate “green” oxidant H2O2, instead requiring peroxycarboxylic acids (2–4 equiv, best results coming with m-CPBA). Herein, we show that hydrogen peroxide itself, conveniently delivered as its solid surrogates (UHP and SPC), can serve as the terminal oxidant in Pd(TPA)-catalyzed nondirected C(sp3)–H oxygenation, with carboxylic acid anhydrides as cocatalytic H2O2 activators. Depending on the conditions, alcohols or ketones form, with the catalyst sustaining up to 1.6 × 104 turnovers. The protocol is applied to the selective oxidation of complex natural products (steroids and terpenoids).