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Title: Understanding of Cu-catalysed coupling reactions for C-N bond formation
Author: Sung, Simon
ISNI:       0000 0004 6423 1369
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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The rate of reaction for the copper-catalysed coupling reactions to form C–N bonds between aryl halides and amines can be significantly improved in the presence of various bidentate ligands. This improved reaction is often referred as the modified Ullmann amination reaction. However the intermediates and steps involved in the mechanism and the role of the ligand are not fully understood. In this work, mechanistic studies have been carried out in order to improve the current understanding of this reaction. The role of copper(I) alkylamide complexes as potential intermediates in the modified Ullmann reaction between aryl halides and alkylamines is discussed in Chapter 2. A series of copper(I) alkylamide complexes have been synthesised and shown using single crystal X-ray crystallography to exist as tetramers in the solid state. The structures of these complexes in benzene-d6 were determined by 1H DOSY NMR spectroscopy which revealed equilibrating aggregates, where the equilibrium rate could be faster or slower than the NMR time scale, with average aggregation numbers between the dimeric and tetrameric forms. The complexes have been shown to react stoichiometrically with iodobenzene to give arylamine products, both in the absence and presence of 1,10-phenanthroline as an ancillary ligand. The influence of 1,10-phenanthroline on the solution structures in benzene-d6 and DMSO-d6 is also discussed and can be related to the stoichiometric and catalytic reactivity. Overall these results highlight the role of copper(I) alkylamide complexes as potential intermediates and show the significance of 1,10-phenanthroline in modulating the reactivity of the system. Chapter 3 describes the improvement in product yield from utilising O,O- and N,O-chelating ligands over N,N-chelating ligands in the copper-catalysed C–N cross-coupling reaction between piperidine and iodobenzene. A kinetic study of this reaction using 2-acetylcyclohexanone as the added ligand demonstrated that the poorly soluble potassium phosphate base caused the reaction rate to be limited by mass transfer effects. The results provide insights into the qualitative rate dependences in the reactants and also the role of the ligand in the catalyst deactivation pathway by disproportionation. A mechanistic study of the copper-catalysed C–N cross-coupling reaction between piperidine and iodobenzene using bis(tetra(n-butyl)phosphonium) malonate as a soluble base is presented in Chapter 4. A detailed kinetic study using reaction calorimetry and the reaction progress kinetic analysis (RPKA) methodology reveals first order rate dependences in the substrates and copper catalyst concentration, and negative first order kinetics in the base concentration. NMR spectroscopic evidence suggests the malonate base simultaneously functions as an ancillary ligand and coordinates to give an off-cycle unstable species. Catalyst deactivation by disproportionation was found to be an important consequence of malonate ligand coordination, with the piperidine substrate playing a key role in mitigating the rate of catalyst deactivation. The absence of aryl radical formation suggests that the aryl halide activation mechanism occurs by an oxidative addition process. The experimental data has been successfully modelled to the proposed mechanism to give approximate equilibrium and rate constants for each step.
Supervisor: Davies, Robert ; Braddock, Chris ; Armstrong, Alan Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral