A Comparative Study of HAT-Based Reactivity Promoted by PINO and Cumyloxyl Radicals and by Photoexcited Decatungstate: Reactivity Scales for C–H Bond Functionalization

The functionalization of non-activated C(sp3)−H bonds is a hot topic in chemistry due to the intrinsic atom and step economy. This process is a powerful tool for late-stage diversification/functionalization of complex derivatives avoiding challenging de novo syntheses. The main drawback of this route is the ubiquity and strength of C(sp3)−H bonds, making their selective functionalization a Holy Grail in chemistry. A smart approach to tackle this issue is provided by hydrogen atom transfer (HAT) reactions, where a radical or radical-like reagent X•, is able to cleave homolytically a C–H bond from a given substrate to deliver a carbon-centered radical for the forging of a C–Y bond under mild conditions. Oxygen-centered HAT reagents are among the elective abstracting species due to their marked electrophilicity and strength of the O–H bond formed following HAT. The aim of this work is to provide an extensive compilation of HAT rate constants (kH values) for the reaction of three selected oxygen-centered hydrogen atom abstractors, namely cumyloxyl radical (CumO•), phthalimide N-oxyl (PINO) radical and decatungstate anion in its excited state (DT*). The resulting comparative analysis of the reactivity and selectivity trends observed in the reactions promoted by the three HAT reagents can provide a valuable set of information to aid in the development of synthetically useful HAT-based C–H functionalization procedures.