Chemoselective Tertiary C−H Hydroxylation for Late‐Stage Functionalization with Mn(PDP)/Chloroacetic Acid Catalysis

Aromatic and heterocyclic functionality are ubiquitous in pharmaceuticals. Herein, we disclose a new Mn(PDP) catalyst system using chloroacetic acid additive capable of chemoselectively oxidizing remote tertiary C(sp3)−H bonds in the presence of a broad range of aromatic and heterocyclic moieties. Although catalyst loadings can be lowered to 0.1 mol% under a Mn(PDP)/acetic acid system for aromatic and non‐basic nitrogen heterocycle substrates, the Mn(PDP)/chloroacetic acid system generally affords 10–15% higher isolated yields on these substrates and is uniquely effective for remote C(sp3)−H hydroxylations in substrates housing basic nitrogen heterocycles. The demonstrated ability to perform Mn(PDP)/chloroacetic acid C(sp3)−H oxidations in pharmaceutically relevant complex molecules on multi‐gram scales will facilitate drug discovery processes via late‐stage functionalization.