Computational mechanistic analysis of homogeneous copper-catalysed Ullmann type coupling reactions.

Abstract

This project aims to critically review past work exploring the mechanism of homogeneously catalysed coupling reactions whilst exploring the use of amino alcohol ligands in copper-mediated Ullmann-type arylation reactions. The use of Cu(I) and Cu(III) assumes an oxidative addition – reductive elimination mechanism. The coordination sphere of Cu(I) was found to optimise towards 2- and 3- coordinate complexes, with 14-electron 2-coordinate complexes being favourable. Cu(III) can be difficult to isolate experimentally and has also been seen to be problematic to locate computationally due to the inaccessibility of a 5-coordinate geometry for copper in this oxidation state, but calculations showed that it may be viable. The most likely mechanism according to the calculations presented here focuses on a 4-coordinate pathway, which benefits from low steric strain and is accessible as a result of the hemilabile nature of amino alcohols. This pathway shares some similarities such as coordination sphere and solvent with other mechanistic proposals but has a focus on this lower coordination number throughout.
Data mining of the Cambridge Structural Database (CSD) was used to gain a greater understanding of the current abundance of copper species and provided an insight into some of the crystal structure of isolated copper complexes with varying oxidation states.
Solvation, dispersion, basis set and functional effects on the relative free energy and geometry have been assessed to determine a ‘best method’ for computational analysis in this project, with compromises being made to manage computational costs. The B3LYP density functional was found to be a robust choice for these calculations. For energies, the 6-311+G(d,p) basis set was identified as a suitable basis set for all atoms except Cu and I which were modelled using the SDD basis set with an Effective Core Potential (ECP). Solvation was modelled implicitly using the IEFPCM method and dispersion was corrected for using the GD3 method.
The proposed mechanism is energetically viable compared with proposed mechanisms in literature and shows evidence that copper coordinated with an amino alcohol is in fact catalytically competent, at least from a computational point of view. The use of 2-coordinate Cu(I) complexes requires further investigation as they show promising results in terms of providing a kinetically-favourable route to oxidative addition.

Date of Award	12 May 2022
Original language	English
Awarding Institution	University of Bristol
Supervisor	Natalie Fey (Supervisor) & Robin B Bedford (Supervisor)