The design of PINO-like hydrogen-atom-transfer catalysts

Phthalimide- N -oxyl (PINO) is a valuable hydrogen-atom-transfer (HAT) catalyst for selective C–H functionalization. To advance and optimize PINO-catalysed HAT reactions, researchers have been focused on modifying the phthalimide core structure. Despite much effort and some notable advances, the modifications to date have centred on optimization of a single parameter of the catalyst, such as reactivity, solubility or stability. Unfortunately, the optimization with respect to one parameter is often associated with a worsening of the others. The derivation of a single catalyst structure with optimal performance across multiple parameters has therefore remained elusive. Here we present an analysis of the structure–activity relationships of PINO and its derivatives as HAT catalysts, which we hope will stimulate further development of PINO-catalysed HAT reactions and, ultimately, lead to much improved catalysts for real-world applications. Hydrogen atom transfer has an expanding role in synthesis, enabling direct C–H functionalization. This Review highlights the state-of-the-art design of phthalimide- N -oxyl catalysts, aiming to stimulate the development of the next generation of efficient and selective catalysts.