The Quest for Selectivity in Hydrogen Atom Transfer Based Aliphatic C–H Bond Oxygenation

Aliphatic C–H bond functionalization is at the frontline of research because it can provide straightforward access to simplified and cost-effective synthetic procedures. A number of these methodologies are based on hydrogen atom transfer (HAT), which, as a consequence of the inert character of C–H bonds, often represents the most challenging step of the overall process. Because the majority of organic molecules contain multiple nonequivalent C–H bonds that display similar chemical properties, differentiating between these bonds with high levels of selectivity represents one of the most challenging issues. Clarification of the factors that govern the relative reactivity of C–H bonds toward HAT reagents is thus of primary importance in order to develop selective functionalization procedures.In this Account we describe, through the combination of kinetic studies employing a genuine HAT reagent such as the cumyloxyl radical, along with oxidations performed with H2O2 and iron or manganese catalysts, our contri...