Visible Light-Mediated Synthesis of Nitrogen-Containing Molecules: Photoredox Generation of Amidyl and Aminium Radicals and Nitrile Oxides

  • Thomas Svejstrup

Student thesis: Phd


Nitrogen-centred radicals (NCRs) are a versatile class of reaction intermediates that can lead to useful synthetic transformations. Classical generation of NCRs requires pre-functionalised precursors that can be difficult to access and requires harsh reaction conditions in the formation of the NCR itself, which had limited synthetic application and interest. With the emergence of visible-light mediated photoredox catalysis as a method for the generation of radicals, interest in NCRs has been renewed. In this thesis, the generation of amidyl and aminium radicals is demonstrated and their application for the advancement of NCR chemistry has been achieved. Initial work utilised electron-poor O-aryl hydroxamic acids as suitable precursors for hydroamidation reactions, activated via single-electron reduction under photoredox conditions. These precursors are accessible by a variety of routes using commercially available reagents. This transformation was a transition metal-free protocol, made possible by using the organic dye eosin Y as the photocatalyst. The use of electron-poor O-aryl electrophores was then extended to the generation of aminium radicals from easy-to-make O-aryl hydroxylamines. The synthesis of arylamines was achieved by polarised radical addition of the aminium radical to arenes. This was achieved in the presence of Ru(bpy)3, blue light, and a strong acid, HClO4. This methodology was applied in the synthesis of a wide range of arylamines with examples in the late stage modification of drugs. Additionally, visible-light photoredox catalysis enabled the synthesis of biologically relevant isoxazolines and isoxazoles from nitrile oxides. This is achieved by two sequential oxidative single electron transfers with hydroxyimino acids, which are bench stable and can easily be synthesised by a simple condensation reaction, to generate the desired nitrile oxide intermediate. These nitrile oxides undergo [3+2] cycloadditions and this methodology shows broad functional group compatibility and provides a new route able to an important class of compounds.
Date of Award31 Dec 2018
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorMichael Greaney (Supervisor) & Daniele Leonori (Supervisor)

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