Mechanistic studies on three areas of organic chemistry - a combined computational and experimental approach

Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2020
Thesis identifier
  • T15590
Person Identifier (Local)
  • 201667896
Qualification Level
Qualification Name
Department, School or Faculty
  • This Thesis contains three results chapters. The underlying aim of these project chapters is to gain a detailed understanding of reaction mechanisms and to develop new synthetic methods based on this knowledge. The three results chapters come under the following titles. Organic Super Electron Donors Made Catalytic (Chapter 2) Neutral organic super electron donors are versatile and powerful reducing agents. So far, however, it has not been possible to use such electron donors in a catalytic sense. Also, many of these donors show significant limitations when applied in radical cascade reactions. This limitation is due to the fact that these donors form relatively long-lived radical cation species upon oxidation, which interfere with the desired radical reaction. The reason for this behaviour is, that the established classes of neutral organic electron donors are (potential) double electron donors. To address these shortcomings, this Thesis reports ways to generate and utilise neutral organic single electron donors (Scheme IV-I). According to the envisaged scheme, the organic single electron donor (i) is generated as an intermediate in a radical chain reaction. The hydrogen abstraction from (iii) by the generated radical, •R’, is the chain propagation step. It becomes evident that the scheme harbours the possibility to use the single electron donor (i) catalytically. The aminal (iii) is regenerated from the benzimidazolium salt (ii) and a hydride source. Sodium borohydride was found to be the ideal hydride source. The protocol was used to perform a range of 5-exo-trig radical cyclisation reactions and its applicability is demonstrated. Based on a combined experimental and computational approach, a plausible initiation pathway based on oxygen in the air is proposed. [Graphic here - Scheme IV-I The proposed scheme for catalytic use of an organic single electron donor (i).] The KOtBu-Et3SiH Reagent System (Chapter 3) The combination of silanes and potassium tert-butoxide allows for various different transformations. Accordingly, several mechanistic pathways and key reactive species have been proposed to account for the different reactions in the literature (Figure IV-I). Hydride transfer mechanisms have been suggested to involve the silicate (iv), which is in equilibrium with potassium hydride (v) and silyl ether (vi). Plausible radical and single electron transfer mechanisms involve (vii) and (viii). Finally, hydrogen atom transfer mechanisms via (ix) cannot be fully excluded as alternatives for many of the discussed mechanisms. The formidable challenge is to probe these different domains of reactivity separately with suitable substrates. Based on a combined approach of experimental and computational investigations, strong indications are reported for single electron transfer reactivity (presumably with species (viii) acting as the single electron donor) and hydride transfer mechanisms. Additionally, plausible mechanisms for the silylation reaction of amines (x) to give the silylated species (xi) are proposed based on computational studies (Scheme IV-II). [Graphic here - Figure IV-I Proposed key species that are responsible for the reactivity of the KOtBu-Et3SiH reagent system.] [Graphic here - Scheme IV-II What is the mechanism of the silylation reaction of simple amines with the KOtBu-Et3SiH (or more generally the KOtBu-Silane) reagent system?] Concerted vs. Stepwise SNAr Mechanism (Chapter 4) Over the last decades, more and more reports accumulated in the literature that suggested certain SNAr reactions follow a concerted pathway. These days, the combined impact of these investigations has reached a critical momentum and it seems appropriate to fundamentally question the long established mechanistic picture of the SNAr reaction. High level computational (wave-function based) methods are here employed to benchmark DFT functionals, based on whether these correctly predict the mechanism of a SNAr reaction to be stepwise or concerted. A reliable functional is then used to establish trends, which show what aspects (nucleophile, counter cation, leaving group, aromatic system) of the reaction at hand influence its mechanistic propensity, and in what way. Eventually this allowed estimation of when an SNAr reaction follows a concerted and when a stepwise pathway is taken.
Advisor / supervisor
  • Murphy, John
Resource Type
  • This thesis was previously held under moratorium from 01/04/2020 to 01/04/2022
Date Created
  • 2020
Former identifier
  • 9912790893402996
Embargo Note
  • This thesis is restricted to Strathclyde users only until 1st April 2025.