Abstract
Chapter 1 introduces the use of iron catalysis and its many benefits specifically for use in both nitro reductions and reductive functionalisation reactions of nitroarenes. In light of this Chapter 2 focuses on the iron-catalysed reduction of both aliphatic and aromatic nitro-compounds. Following on from an examination of the reaction conditions and reaction scope, an extensive mechanistic study was conducted using a range of techniques including kinetic studies, EPR, radical trapping experiments and quantum chemistry. The results of this study led to a postulated mechanism that proceeds via two interlinked catalytic cycles via a key Fe-hydride active catalyst. The investigation also revealed a nitroso intermediate is likely to be the key product of the first cycle.Following on from this Chapter 3 details the investigation into whether reactivity obtained by use of an iron(salen) pre-catalyst in combination with a reductant could be extended to facilitate a one-pot hydroamination reaction. By use of a simple molecular-orbital based predictor, determined by computational analysis, the suitability of a variety of alkenes for the use in the hydroamination reaction were assessed. Continuing from this, the scope of the reaction was further probed, and several control reactions were conducted to try and gain evidence for the presence of the key hydrogen atom transfer step.
The iron-catalysed hydroamination reaction was explored further in Chapter 4. This research focused on the high levels of electronic tuning available through salen ligand modification. Altering the ligand backbone saw a significant change to the electronics at the iron centre which led to the subsequent discovery that both the presence of an electron withdrawing group and an electron donating group on the standard ligand scaffold appeared to improve the selectivity for hydroamination reactions compared to the standard backbone. To further explore the trends observed in reactivity, computational analysis was performed on the various iron hydride species to determine both the singly occupied molecular orbital value and the bond dissociation free energy of the key mechanistic steps.
In Chapter 5, focus moves away from iron-based catalysis, towards an investigation into whether a simple organic method could be utilised to trap out the highly reactive methanimine species. The use of an in-situ Diels–Alder reaction to trap out methanimine as simple piperidine based N-heterocycles was explored. Subsequent investigations into alternative dienes revealed that the steric and electronic nature of the diene had a great effect on its effectiveness at trapping methanimine. While the yields of the resultant N-heterocycles were modest, the products formed were novel yet structurally simple and could be envisioned to be highly synthetically useful building blocks for further transformations.
| Date of Award | 26 Mar 2025 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Simon Lewis (Supervisor), Ruth Webster (Supervisor), Michael Nunn (Supervisor) & Andrew Johnson (Supervisor) |