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

Zars E, Muhm SP, Pick L, Bhunia M, Gau MR, Munz D, Meyer K, Mindiola DJ (2026)

Publication Type: Journal article

Publication year: 2026

Journal

ACS Catalysis American Chemical Society

Book Volume: 16

Pages Range: 8957-8970

Article Number: e202311749

Journal Issue: 10

DOI: 10.1021/acscatal.5c09143

Abstract

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)2pyr^2– = 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.; et al. 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 1^st 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))Fe^tBupyrrpyr(2-H-pyrr)] (5^iPr). Quantum chemical calculations confirm the electronic structure of the mixed-valence dimer in 5^iPr 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.

Authors with CRIS profile

Lisa Pick Lehrstuhl für Anorganische und Allgemeine Chemie Karsten Meyer Lehrstuhl für Anorganische und Allgemeine Chemie

Involved external institutions

University of Pennsylvania (UPenn)

United States (USA) (US) Universität des Saarlandes (UdS)

Germany (DE)

How to cite

APA:

Zars, E., Muhm, S.P., Pick, L., Bhunia, M., Gau, M.R., Munz, D.,... Mindiola, D.J. (2026). Mechanistic Studies of an Iron-Catalyzed Intermolecular C–H Amination Reaction under Catalytic Conditions and Having a Large KIE. ACS Catalysis, 16(10), 8957-8970. https://doi.org/10.1021/acscatal.5c09143

MLA:

Zars, Ethan, et al. "Mechanistic Studies of an Iron-Catalyzed Intermolecular C–H Amination Reaction under Catalytic Conditions and Having a Large KIE." ACS Catalysis 16.10 (2026): 8957-8970.

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