Nitrene transfer from a sterically confined copper nitrenoid dipyrrin complex

Despite the myriad Cu-catalyzed nitrene transfer methodologies to form new C-N bonds (e.g., amination, aziridination), the critical reaction intermediates have largely eluded direct characterization due to their inherent reactivity. Herein, we report the synthesis of dipyrrin-supported Cu nitrenoid adducts, investigate their spectroscopic features, and probe their nitrene transfer chemistry through detailed mechanistic analyses. Treatment of the dipyrrin Cu^I complexes with substituted organoazides affords terminally ligated organoazide adducts with minimal activation of the azide unit as evidenced by vibrational spectroscopy and single crystal X-ray diffraction. The Cu nitrenoid, with an electronic structure most consistent with a triplet nitrene adduct of Cu^I, is accessed following geometric rearrangement of the azide adduct from κ¹-N terminal ligation to κ¹-N internal ligation with subsequent expulsion of N₂. For perfluorinated arylazides, stoichiometric and catalytic C-H amination and aziridination was observed. Mechanistic analysis employing substrate competition reveals an enthalpically-controlled, electrophilic nitrene transfer for primary and secondary C-H bonds. Kinetic analyses for catalytic amination using tetrahydrofuran as a model substrate reveal pseudo-first order kinetics under relevant amination conditions with a first-order dependence on both Cu and organoazide. Activation parameters determined from Eyring analysis (ΔH^‡ = 9.2(2) kcal mol^-1, ΔS^‡ = -42(2) cal mol^-1 K^-1, ΔG^‡_298K = 21.7(2) kcal mol^-1) and parallel kinetic isotope effect measurements (1.10(2)) are consistent with rate-limiting Cu nitrenoid formation, followed by a proposed stepwise hydrogen-atom abstraction and rapid radical recombination to furnish the resulting C-N bond. The proposed mechanism and experimental analysis are further corroborated by density functional theory calculations. Multiconfigurational calculations provide insight into the electronic structure of the catalytically relevant Cu nitrene intermediates. The findings presented herein will assist in the development of future methodology for Cu-mediated C-N bond forming catalysis.