The mechanisms of a range of cross-coupling reactions catalysed by cheaper metal catalysts have been investigated in detail using a combination of spectroscopic techniques and computational modelling. For iron-catalysed Negishi cross-coupling reactions supported by phosphine ligands, it is shown that the iron(II) pre-catalysts are reduced in situ to iron(I), which is found to be the only kinetically relevant oxidation state. The characterisation of a range of relevant low-spin iron(l) phosphine complexes has allowed the study of the mechanism in significantly greater detail than before via direct detection of in situ formed iron(I) intermediates using EPR and UV-Vis spectroscopy. Through the study of reaction kinetics, an Eyring analysis and detailed computational modelling, it has been possible to determine the most likely mechanism for the oxidative addition of the electrophile during cross-coupling. The importance of spin-state changes has been demonstrated through computational modelling; only the involvement of high-spin intermediates, arising from the lowspin ground state, can permit the observed rates. iron-catalysed cross-coupling reactions using amine ligands or ligand-free conditions have been shown to behave in a very different manner to those employing phosphine ligands, with a further clear distinction between systems using aryl- and alkyl-based nucleophiles. The use of alkyl nucleophiles containing β-hydrogen atoms leads to immediate decomposition of iron intermediates, whilst the use of β-hydrogen-free alkyl nucleophiles give thermally stable homoleptic 'ate' complexes including [FeBn₃] and [FeBn₄]. Two classes of intermediates are formed simultaneously from aryl based nucleophiles; a thermally stable iron(I) complex proposed as [Fe(ɳ⁶-(4,4'-bitoly)4-tolyl)₂], and thermally labile homoleptic iron(II) 'ate' complexes including [Fe(4-tolyl)₃] and [Fe(4-tolyl)₄]². Crucially, the identity of the metal in the nucleophile is central to the observed reactivity. Computational modelling has been used to investigate the mechanism of transmetallation and aryl transfer in mixtures of boronic acids, diethylzinc and benzyl halides to form diarylmethanes. It is proposed that transmetallation between boron and zinc occurs by direct alkyl and aryl transfer via boron-zinc zwitterionic-like intermediates. The calculated distribution of organoboron and zinc intermediates based on this mechanism in a range of solvents is in good agreement with existing experimental results. A number of potential mechanisms have been considered, using computational modelling, in the coupling of benzyl bromide with mixtures of diethylzinc and aryl boronic acids.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:687059 |
| Date | January 2014 |
| Creators | Nunn, Joshua |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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