Thesis

The development of chemo- and regioselective reactions of boron systems

Creator
Rights statement
Awarding institution
  • University of Strathclyde.
Date of award
  • 2017
Thesis identifier
  • T15983
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • This thesis describes an evolution in the chemo- and regioselective reactions of boron species. The first chapter details the chemoselective oxidation of an aryl organoboron species in the presence of a second oxidisable aryl organoboron moiety (Scheme 0.01). [Graphic here title :Scheme 0.01 Chemoselective oxidation of aryldiboron systems.] Comprehensive reaction optimisation led to the discovery of basic biphasic reaction conditions where, upon further analysis, selective boronic acid boronate formation occurs enabling the differentiation of boron species. Furthermore, inversion of conventional protecting group strategies can be facilitated by the biphasic system, allowing for the chemoselective oxidation of boronic acid, N-methyliminodiacetic acid (BMIDA) species over normally more reactive boronic acid pinacol (BPin) ester substrates. Chemoselective oxidation can be further expanded to diboronic acid systems where the extent of chemoselectivity can be predicted via prior HPLC analysis. The second chapter focuses on the use of new technologies in a drug discovery environment. In particular the use of COware, a two-chamber glassware system for the in situ production and consumption of low molecular weight gases, and the role that it can play in facilitating multistep reaction sequences in one-pot. This idea was exemplified by achieving a high-yielding, one-pot regioselective Suzuki-Miyaura/hydrogenation reaction sequence (Scheme 0.02) [Graphic here title :Scheme 0.02 Synthesis of substituted tetrahydropyridopyrimidines enabled by COware.]. The use of COware technology allows for a simple experimental procedure. Expedient access to a plethora of motifs demonstrates the applicability of this approach to a drug discovery environment. The resulting bicyclic core contains two sites of orthogonal reactivity for further synthetic manipulation. The applicability of COware methodology was further demonstrated in the syntheses of two semisaturated inhibitors from the literature (Scheme 0.03). [Graphic here title : Scheme 0.03 One-pot PI3K/mTOR inhibitor synthesis.].
Advisor / supervisor
  • Watson, Allan
  • Anderson, Niall
Resource Type
Note
  • Previously held under moratorium in Chemistry department (GSK) from 26/10/17 until 3 September 2021.
DOI
Funder
Embargo Note
  • This thesis is restricted to Strathclyde users only until 26th October 2022.

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