Abstract
<jats:p> <jats:italic toggle="yes">N</jats:italic> -hydroxyphthalimide (NHPI) and its corresponding <jats:italic toggle="yes">N</jats:italic> -oxyl radical, phthalimide <jats:italic toggle="yes">N</jats:italic> -oxyl (PINO), have long been used as mediators for hydrogen atom transfer (HAT), particularly in radical-mediated C–H oxidations. Although numerous NHPI/PINO derivatives have been developed, the absence of an intuitive model connecting scaffold structure to intrinsic HAT reactivity has left catalyst development largely empirical. Herein, we show that inserting a heteroatom between one carbonyl group of the NHPI/PINO framework and the fused aryl ring substantially accelerates HAT in electrochemically driven oxidations, with rate enhancements of up to 36-fold for benzylic alcohol substrates. This enhanced reactivity correlates with significantly larger computed O–H bond dissociation enthalpies relative to NHPI (ΔBDE <jats:sub>O-H</jats:sub> = 6.5-8.1 kcal/mol), which increase the thermodynamic driving force for HAT by the corresponding <jats:italic toggle="yes">N</jats:italic> -oxyl radicals. NICS, NBO, and DFT-based structural analyses support a model in which previously overlooked antiaromatic destabilization within the five-membered imide motif weakens the O–H bond of NHPI and is relieved upon formation of PINO. Among the heteroatom-containing analogues examined, sulfur-containing <jats:italic toggle="yes">N</jats:italic> -hydroxythiobenzouracil (NHTBU) provided a favorable balance of high HAT reactivity and catalyst persistence, enabling the electrochemical oxidation of numerous substrates under mild conditions with activity superior to NHPI. </jats:p>