Mechanistic Studies of an Iron-Catalyzed Intermolecular C–H Amination Reaction under Catalytic Conditions and Having a Large KIE

The conversion of C–H bonds into amines by nitrene insertion is an attractive transformation since it is both atom- and step-economical, and provides a direct route to functionalizing hydrocarbons. Using an iron catalyst [{(tBupyrr)2pyr}Fe(OEt2)] (1-OEt2) ((tBupyrr)2pyr2– = 3,5-tBu2-bis(pyrrolyl)pyridine), we recently demonstrated the catalytic conversion of weak C–H bonds into secondary amines using aryl azides as the nitrene source [Zars, E.; Angew. Chem., Int. Ed. 2023, 62, e202311749]. Here, we describe detailed mechanistic studies of this intermolecular C–H amination reaction under catalytic conditions. We find by Variable Time Normalization Analysis (VTNA) that the conversion of xanthene (2-H2) and 2,4,6-trimethyl-phenyl azide (Me3) catalyzed by 1-OEt2 is an overall 3/2 order process, being 1st order in 2-H2 and half order in Me3. A kinetic isotope effect study (KIE) using 2-d2 results in a significant decrease in the rate (KIE = 61(15)), which clearly implicates the C–H insertion step as rate-determining. Furthermore, treatment of 1-OEt2 with one equivalent of N3-2,6-iPr2–C6H3 yields the mixed-valence C–N coupled product [(tBupyrr)2pyrFe-N═C(2,6iPr2–Ph)═N-(2,6iPr2–Ph))FetBupyrrpyr(2-H-pyrr)] (5iPr). Quantum chemical calculations confirm the electronic structure of the mixed-valence dimer in 5iPr and rationalize the Hammett correlation by a delicate balance in the dinuclearization of the catalytically active monomers. Calculations further indicate significant tunneling for the pivotal H atom abstraction by the iron-imidyl complex. Combining all these results allows us to propose a mechanism consisting of imido formation in equilibrium with a radical-coupled diiron system, followed by stepwise C–H insertion via a linear H atom abstraction transition state and subsequent radical rebound.