Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug 9;40(15):2467-2477.
doi: 10.1021/acs.organomet.1c00211. Epub 2021 Jul 20.

Mechanistic Insights into Iron-Catalyzed C-H Bond Activation and C-C Coupling

Samantha M Brewer  1 , Timothy M Schwartz  1 , Magy A Mekhail  1 , Lara S Turan  1 , Timothy J Prior  2 , Timothy J Hubin  3 , Benjamin G Janesko  1 , Kayla N Green  1
Affiliations

Mechanistic Insights into Iron-Catalyzed C-H Bond Activation and C-C Coupling

Samantha M Brewer et al. Organometallics. .

Abstract

Iron-catalyzed C-C coupling reactions of pyrrole provide a unique alternative to the traditional Pd-catalyzed counterpart. However, many details regarding the actual mechanism remain unknown. A series of macrocyclic iron(III) complexes were used to evaluate specifics related to the role of O2, radicals, and μ-oxodiiron-complex participation in the catalytic cycle. It was determined that the mononuclear tetra-azamacrocyclic complex is a true catalyst and not a stoichiometric reagent, while more than one equivalent of a sacrificial oxidant is needed. Furthermore, the reaction does not proceed through an organic radical pathway. μ-Oxodiiron complexes are not involved in the main catalytic pathway, and the dimers are, in fact, off-cycle species that decrease catalytic efficiency.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1.
Scheme 1.
General Reaction for the Coupling of Phenylboronic Acid and Pyrrole
Figure 1.
Figure 1.
Chemical structure of ligands L1−L5 and complexes [FeL1−L5(Cl)2]+.
Scheme 2.
Scheme 2.. Synthesis of 3-Pyrroline-2-one as a Potential Starting Material for Pyrrole and Phenylboronic Acid Couplinga
a2-phenylpyrrole is not produced when [FeL2(Cl)2]Cl was used for catalysis.
Figure 2.
Figure 2.
DPPH assay showing radical-scavenging ability relative to radicals remaining for [FeL1(Cl)2]ClO4, [FeL2(Cl)2]ClO4, and [FeL3(Cl)2]ClO4.
Scheme 3.
Scheme 3.
Synthesis of Structures of 1a, 1b, and 2 Dimers and 3 Tetrametallic Species
Figure 3.
Figure 3.
ORTEP representation of solid-state structures of 1a, 1b, and 2, described in Scheme 2. Counterions and solvent molecules have been removed for clarity. Atoms are drawn as 50% probability ellipsoids.
Figure 4.
Figure 4.
(A) ORTEP plot of the asymmetric unit of 3. Atoms are shown as 30% probability ellipsoids. The PF6− anion is not included for clarity. (B) Tetranuclear cluster present in [Fe(Cl){(μ-O)FeL5Cl}3](PF6)2. Anions and hydrogen atoms (on A) are not shown. Symmetry operations used to generate equivalent atoms: (i) = 2 − y, 1 + x − y, z; (ii) = 1 − x + y, 2 − x, z.
Figure 5.
Figure 5.
(a) Visible spectra of 1a in MeOH (dashed-line), [FeL1(Cl)2]+ in 8% H2O/MeOH (dotted-line), and [FeL1(Cl)2]+ in 8% H2O/MeOH/25 μL acid (solid-line). (b) Visible absorption spectra of [FeL1(Cl)2]+ in CH3CN (orange) and 8% H2O/MeOH solution after addition of concentrated HCl (25 μL, black). (c) [FeL1(Cl)2]+ (0.13 mM/0.94 mM, green) and 1a (0.13 mM/0.99 mM, purple); (d) [FeL4(Cl)2]+ (0.16 mM/1.0 mM, green) and 2 (0.12 mM/1.0 mM, purple) in CH3CN.
Scheme 4.
Scheme 4.. More Detailed Catalytic Mechanism Proposed for the Iron-Catalyzed C−C Coupling of Pyrrole and Phenylboronic Acida
aActive cycle (outlined in green) based on refs and .
See this image and copyright information in PMC

References

    1. Miyaura N; Suzuki A Stereoselective synthesis of arylated (E)-alkenes by the reaction of alk-1-enylboranes with aryl halides in the presence of palladium catalyst. J. Chem. Soc., Chem. Commun 1979, 19, 866–867.
    1. Miyaura N; Yamada K; Suzuki A A new stereospecific crosscoupling by the palladium-catalyzed reaction of 1-alkenylboranes with 1-alkenyl or 1-alkynyl halides. Tetrahedron Lett. 1979, 20, 3437–3440.
    1. Wu G; Jacobi von Wangelin A Iron-catalysed Suzuki biaryl couplings. Nat. Catal 2018, 1, 377–378.
    1. Shang R; Ilies L; Nakamura E Iron-Catalyzed C−H Bond Activation. Chem. Rev 2017, 117, 9086–9139. - PubMed
    1. Andrews NC Disorders of Iron Metabolism. N. Engl. J. Med 1999, 341, 1986–1995. - PubMed

LinkOut - more resources