Catalytic Synthesis of N-Heterocycles via Direct C(sp3)-H Amination Using an Air-Stable Iron(III) Species with a Redox-Active Ligand

Bidraha Bagh; Daniël L J Broere; Vivek Sinha; Petrus F Kuijpers; Nicolaas P van Leest; Bas de Bruin; Serhiy Demeshko; Maxime A Siegler; Jarl Ivar van der Vlugt

doi:10.1021/jacs.7b00270

Catalytic Synthesis of N-Heterocycles via Direct C(sp³)-H Amination Using an Air-Stable Iron(III) Species with a Redox-Active Ligand

J Am Chem Soc. 2017 Apr 12;139(14):5117-5124. doi: 10.1021/jacs.7b00270. Epub 2017 Mar 28.

Authors

Bidraha Bagh¹, Daniël L J Broere¹, Vivek Sinha¹, Petrus F Kuijpers¹, Nicolaas P van Leest¹, Bas de Bruin¹, Serhiy Demeshko², Maxime A Siegler³, Jarl Ivar van der Vlugt¹

Affiliations

¹ Homogeneous, Bioinspired and Supramolecular Catalysis, van't Hoff Institute for Molecular Sciences, University of Amsterdam , Science Park 904, 1098 XH, Amsterdam, The Netherlands.
² Institüt für Anorganische Chemie, Georg-August-Universität Göttingen , Tammannstraße 4, 37077 Göttingen, Germany.
³ Small Molecule X-ray Crystallography, Department of Chemistry, Johns Hopkins University , Baltimore, Maryland 21218, United States.

Abstract

Coordination of FeCl₃ to the redox-active pyridine-aminophenol ligand NNO^H2 in the presence of base and under aerobic conditions generates FeCl₂(NNO^ISQ) (1), featuring high-spin Fe^III and an NNO^ISQ radical ligand. The complex has an overall S = 2 spin state, as deduced from experimental and computational data. The ligand-centered radical couples antiferromagnetically with the Fe center. Readily available, well-defined, and air-stable 1 catalyzes the challenging intramolecular direct C(sp³)-H amination of unactivated organic azides to generate a range of saturated N-heterocycles with the highest turnover number (TON) (1 mol% of 1, 12 h, TON = 62; 0.1 mol% of 1, 7 days, TON = 620) reported to date. The catalyst is easily recycled without noticeable loss of catalytic activity. A detailed kinetic study for C(sp³)-H amination of 1-azido-4-phenylbutane (S₁) revealed zero order in the azide substrate and first order in both the catalyst and Boc₂O. A cationic iron complex, generated from the neutral precatalyst upon reaction with Boc₂O, is proposed as the catalytically active species.