Intermediates and Mechanism in Iron-Catalyzed Cross-Coupling

Abstract

Iron-catalyzed cross-coupling reactions have attracted significant research interest, as they offer numerous favorable features compared with cross-coupling reactions with precious metal catalysis. While this research has contributed to an empirical understanding of iron-catalyzed cross-coupling, the underlying fundamental mechanisms of reaction and structures of catalytically active species have remained poorly defined. The lack of such detail can be attributed to the difficulties associated with studying such iron-catalyzed reactions, where unstable paramagnetic intermediates abound. Recently, the combined application of physical-inorganic spectroscopic methods, concomitant organic product analysis, and air- and temperature-sensitive inorganic synthesis has yielded the most detailed insight currently available on reactivity and mechanism in iron-catalyzed cross-coupling. This Perspective highlights this approach and the limitations of the contributing techniques as well as some of the key features of the catalytic reactions studied and lessons learned.

Figure 1.

Iron mechanistic toolbox combining physical-inorganic spectroscopies, low-temperature synthesis, and concurrent iron speciation/reactivity studies.

Figure 2.

Time-resolved, freeze-trapped 80 K ⁵⁷Fe Mössbauer spectra of the reaction of FeMes₂(SciOPP) and 20 equiv of 1-bromodecane to generate FeBrMes(SciOPP) and the cross-coupled product. Adapted from ref . Copyright 2014 American Chemical Society.

Figure 3.

X-ray structure and EPR spectrum of Kochi’s observed S = ½ iron complex. Adapted from ref . Copyright 2016 American Chemical Society.

Figure 4.

Dependence of iron speciation on the addition of MesMgBr in iron-catalyzed cross-coupling of MesMgBr and alkyl halides.

Figure 5.

Precatalyst generation step for iron-NHC catalyzed alkyl–alkyl cross coupling including freeze-trapped EPR spectrum which is unable to observe the majority of in situ iron and the crystal structure of bis-alkyl iron-NHC species found to be the major precatalyst species generated in solution. Adapted with permission from ref , published by the Royal Society of Chemistry.

Figure 6.

80 K ⁵⁷Fe Mössbauer spectrum containing the major species FeMes₂(SciOPP) and FeBrMes(SciOPP) (Ar = 3,5-tert-butylphenyl). Adapted from ref . Copyright 2014 American Chemical Society.

Figure 7.

Time-resolved, freeze-quenched 80 K ⁵⁷Fe Mössbauer spectra of the reaction of FeBr₂(SciOPP) (Ar = 3,5-tert-butylphenyl) with 1 equiv of (TIPS)ethynylmagnesium bromide at room temperature. Adapted from ref . Copyright 2017 American Chemical Society.

Figure 8.

Methylferrate species generated from the reaction of FeCl₃ with MeLi or MeMgBr under various reaction conditions.

Figure 9.

Bisalkyl iron–NHC species generated in the precatalyst formation step and their performance for catalysis. Adapted with permission from ref , published by the Royal Society of Chemistry.

Scheme 1.

Selected Examples of Iron-Catalyzed Cross-Coupling Methods

Scheme 2.

Examples of Mechanistic Pathways in Iron-Catalyzed Cross-Coupling