Efficient C-H Amination Catalysis Using Nickel-Dipyrrin Complexes

A dipyrrin-supported nickel catalyst (L-AdF) Ni(py) (L-AdF: 1,9-di(1-adamantyl)-5-perfluorophenyldipyrrin; py: pyridine) displays productive intramolecular C-H bond amination to afford N-heterocyclic products using aliphatic azide substrates. The catalytic amination conditions are mild, requiring 0.1-2 mol% catalyst loading and operational at room temperature. The scope of C-H bond substrates was explored and benzylic, tertiary, secondary, and primary C-H bonds are successfully aminated. The amination chemoselectivity was examined using substrates featuring multiple activatable C-H bonds. Uniformly, the catalyst showcases high chemoselectivity favoring C-H bonds with lower bond dissociation energy as well as a wide range of functional group tolerance (e.g., ethers, halides, thioetheres, esters, etc.). Sequential cyclization of substrates with ester groups could be achieved, providing facile preparation of an indolizidine framework commonly found in a variety of alkaloids. The amination cyclization reaction mechanism was examined employing nuclear magnetic resonance (NMR) spectroscopy to determine the reaction kinetic profile. A large, primary intermolecular kinetic isotope effect (KIE = 31.9 +/- 1.0) suggests H-atom abstraction (HAA) is the rate-determining step, indicative of H-atom tunneling being operative. The reaction rate has first order dependence in the catalyst and zeroth order in substrate, consistent with the resting state of the catalyst as the corresponding nickel iminyl radical. The presence of the nickel iminyl was determined by multinuclear NMR spectroscopy observed during catalysis. The activation parameters (Delta H double dagger = 13.4 +/- 0.5 kcal/mol; Delta S double dagger = -24.3 +/- 1.7 cal/mol.K) were measured using Eyring analysis, implying a highly ordered transition state during the HAA step. The proposed mechanism of rapid iminyl formation, rate-determining HAA, and subsequent radical recombination was corroborated by intramolecular isotope labeling experiments and theoretical calculations.