Revisiting the Reactivity of the Dismissed Hydrogen Atom Transfer Catalyst Succinimide-N-oxyl

Phthalimide-N-oxyl (PINO) and related radicals are promising catalysts for C-H functionalization reactions. To date, only a small number of N-oxyl derivatives have demonstrated improved activities over PINO. We postulate that the lack of success in identifying superior catalysts is associated not only with challenges in the design and synthesis of new structures, but also the way catalysts are evaluated and utilized. Catalyst evaluation typically relies on the use of chemical oxidants to generate N-oxyl radicals from their parent N-hydroxy compounds. We put forth an example where a potential-controlled electrochemical analy-sis reveals that succinimide-N-oxyl (SINO) compares favorably to PINO as a hydrogen atom transfer catalyst – in contrast to previous claims based on other approaches. Furthermore, our efforts to understand the basis for the greater reactivity of SINO relative to PINO have shed further light on the interplay of thermodynamic and kinetic factors in these HAT reactions and sug-gest that transition state (TS) polarization is a particularly important consideration. This is illustrated by the essentially identi-cal reactivity of tetrachloro-PINO and SINO despite the significantly greater thermodynamic driving force in the reactions of the latter. Such measures of HAT TS polarization (i.e., proton affinity of the N-oxide anion) may be useful parameters in pre-dicting and/or rationalizing reactivity in addition to reaction energetics (i.e., O-H bond dissociation enthalpy of the N-OH moie-ty). Building on these insights, we report the design and initial characterization of a chlorinated SINO derivative that has signif-icantly greater reactivity as a HAT catalyst than either PINO or its chlorinated derivative.