Investigation into the mechanism of a photoredox catalysed C(sp3)–H functionalisation reaction in continuous flow
File(s)
Author(s)
Broderick, Hannah
Type
Thesis
Abstract
Photoredox-catalysed C(sp3)–H functionalisation is a powerful technique to access derivatized heterocycles with wide functional group tolerance. The kinetics of such reactions are currently poorly understood; orders in components are specific to variables including light intensity, catalyst, concentration, and setup. Flow chemistry can increase control over these variables and achieve higher surface-area-to-volume ratios, enhanced light penetration and improved reproducibility over batch counterparts. This thesis describes the development of a photoredox-catalysed C(sp3)–H functionalisation reaction of N-aryl pyrrolidines with radical acceptors using batch and continuous flow approaches. Investigations into the reaction mechanism are described with a focus on understanding the kinetics of this system.
Section 2.1 describes the optimisation of the batch reaction. However this was found to be insufficiently reproducible for rigorous kinetic analysis, prompting translation to a continuous flow system to obtain kinetic profile data, presented in section 2.2. Mechanistic analysis of the reaction is presented in Section 2.3, including the application of VTNA to obtain a non-light-limited reaction regime used to study rates of different substrates, and to determine components in the apparent reaction rate law.
Kinetic experiments under the non-light-limited reaction conditions, alongside ex situ analytical techniques, were used to determine that single electron transfer between N aryl pyrrolidines and the iridium photocatalyst excited state was turnover-limiting. Investigating the effect of different reactants on reaction rate uncovered trends in the aryl substitution patterns of N-aryl pyrrolidines and different nitrogen heterocycles. This has deepened understanding into the chemistry of radical formation under iridium-catalysed photoredox conditions. Computational investigations sought to explain these trends in oxidation potentials, providing general insights into the formation of α-nitrogen radicals and the chemoselectivity of such transformations. This analysis is presented and discussed in section 2.4, culminating in a summary of the insights into this mechanism obtained throughout this work in the form of rate equations.
Section 2.1 describes the optimisation of the batch reaction. However this was found to be insufficiently reproducible for rigorous kinetic analysis, prompting translation to a continuous flow system to obtain kinetic profile data, presented in section 2.2. Mechanistic analysis of the reaction is presented in Section 2.3, including the application of VTNA to obtain a non-light-limited reaction regime used to study rates of different substrates, and to determine components in the apparent reaction rate law.
Kinetic experiments under the non-light-limited reaction conditions, alongside ex situ analytical techniques, were used to determine that single electron transfer between N aryl pyrrolidines and the iridium photocatalyst excited state was turnover-limiting. Investigating the effect of different reactants on reaction rate uncovered trends in the aryl substitution patterns of N-aryl pyrrolidines and different nitrogen heterocycles. This has deepened understanding into the chemistry of radical formation under iridium-catalysed photoredox conditions. Computational investigations sought to explain these trends in oxidation potentials, providing general insights into the formation of α-nitrogen radicals and the chemoselectivity of such transformations. This analysis is presented and discussed in section 2.4, culminating in a summary of the insights into this mechanism obtained throughout this work in the form of rate equations.
Version
Open Access
Date Issued
2023-12-13
Date Awarded
2024-06-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Bull, James
Miller, Philip
Heinis, Thomas
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)