Kinetics and Equilibrium in Iron-Catalysed Cross-Coupling Reactions

  • Stephen Luckham

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)


Using a range of spectroscopic techniques, insights into the iron-catalysed Kumada and Negishi cross-coupling reactions are proposed. A small study on a chromium-diphosphine complex, using EPR spectroscopy, has also been carried out.
In the case of an iron-catalysed Kumada cross-coupling of a benzyl halide and a benzyl Grignard reagent, a catalytic cycle based on an iron(I)/(II)/(III) centre is proposed. The reaction proceeds unselectively, yielding a distribution of products. From a detailed kinetic investigation, it is found that the rate-limiting step for the formation of each product involves the activation of the electrophile at the iron centre, suggestive of a slow oxidation step and the formation of heteroleptic, iron(III) ‘ate’ species. The results of a Hammett study and an Eyring analysis suggest that this step is likely to occur by a radical pathway, with no thermodynamic preference towards any one of the products. An auto-catalytic pathway is proposed to be operative, based on the sigmoidal nature of the concentration-time plots obtained.
Addition of an NHC ligand to the iron-catalysed Kumada coupling described above is shown, via NMR spectroscopy, to result in a mixed iron speciation, the ratio of which is dependent upon the concentration of the NHC ligand. This is supported by the results of a small kinetic study, which indicates that the iron-NHC complexes perform as slightly more active (though equally unselective) catalysts compared to the ligand-free species.
The transmetallation of iron by zinc-aryl species is shown to occur using both 4-tolyl and mesityl nucleophiles, in the presence and absence of a diphosphine ligand. Using the kinetically stabilised mesityl group, the diphosphine ligand was shown, in a qualitative fashion, to provide a more facile transmetallation process, resulting ultimately in the complete dissociation of the diphosphine ligand from iron, and formation of a series of hetero- and homoleptic ferrate species. Transmetallation is also possible in the absence of magnesium salts, suggesting that their necessary presence within the iron-catalysed Negishi cross-coupling is not concerned with the transmetallation step. The reverse process, whereby transmetallation occurs from iron to zinc, is also shown to be possible. In this case quantification demonstrated the process to proceed efficiently with good yields.
Using NMR and X-ray absorption spectroscopies, the diphosphine ligand within an ironcatalysed Negishi cross-coupling is found to not coordinate to iron during catalytic turnover, residing instead on the zinc centre. Using XAS, a rapid burst-phase at the start of the reaction

is shown to yield metallic iron, following which the iron takes the form of homo- or heteroleptic organo-iron complexes throughout the bulk of turnover. Using 31P NMR spectroscopy, the diphosphine ligand is quantifiably assigned to exist coordinated to zinc throughout the bulk of turnover.
A chromium(I) mono-diphosphine complex is shown to undergo a photochemical transformation, under action of UV irradiation, to yield a Cr(I)-bis-diphosphine complex. An intermediate in the photochemical transformation is identified as a bimetallic complex, featuring a bridging diphosphine ligand between the two chromium(I) centres.
Date of Award1 Oct 2019
Original languageEnglish
Awarding Institution
  • University of Bristol
SupervisorRobin B Bedford (Supervisor) & Damien M. Murphy (Supervisor)

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