Advances in Iron-Catalysed Cross-Coupling Reactions
: Methodology and Mechanism

  • Harry O'Brien

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

The replacement of noble metals with cheap, sustainable and non-toxic iron as catalysts for cross coupling reactions continues unabated. The significant advancement in methodology has been accompanied by elegant mechanistic studies; vital for further reaction development.

Amongst this success, the development of reactions which work with milder coupling partners is paramount. Organoboron reagents are particularly useful, and accordingly there has been great progress in the development of iron-catalysed Suzuki cross-coupling reactions. However, the cross-coupling between an aryl halide and aryl boron reagent, a Suzuki biaryl cross-coupling, has not yet been achieved with iron-catalysis under mild conditions. Here, it is shown that the barrier to success has been in the activation of the aryl halide bond. This has been overcome by installation of an ortho N-pyrrole amide directing group. Notably, mechanistic studies reveal that the N-pyrrole amide works by tethering the iron-catalyst to the electrophile via π-coordination, and a single electron transfer process to afford an amino ketyl radical appears to be responsible for activation of the aryl halide bond.

Asymmetric iron-catalysed cross-couplings are extremely rare, and the seminal example suffers from a restrictive electrophile scope. The enantioconvergent iron-catalysed cross-coupling of an unactivated alkyl halide substrate has also been investigated to broaden the scope of this methodology.

Finally, a combined synthetic and mechanistic study was conducted to compare the activity of an N-heterocyclic carbene ligand with its N-heterocyclic germylene analogue in iron-catalysed cross couplings; affording insights into the role of carbene ligands in iron-catalysis.
Date of Award25 Sep 2018
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorRobin B Bedford (Supervisor)

Cite this

Advances in Iron-Catalysed Cross-Coupling Reactions: Methodology and Mechanism
O'Brien, H. (Author). 25 Sep 2018

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)