Investigations into the Use of Photoredox Catalysis for the Synthesis of Indoloazepinone Scaffolds

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

Different indoloazepinone analogues of the natural product hymenialdisine have been
previously investigated as medicinal compounds).
1-5 The synthesis of
indoloazepinone compounds using an interesting [5+2] photocycloaddition6-8 offered an
alternative synthetic route to these scaffolds. The construction of the azepinedione ring before
the formation of the indole allowed for late-stage diversification of the indole ring.

Utilising the dichloro-azepinedione substrate 1
9
the synthesis of indoloazepinone derivatives
was possible in just two synthetic steps. Regiospecific reaction conditions for the first step, a
conjugate substitution reaction, were successfully developed. A range of differently substituted
anilines were reacted with the dichloro-azepinedione substrate 1 giving yields up to 92%.
Visible light photoredox catalysis methodology was then developed for the final indole forming
step. After investigating a variety of reaction conditions, fac-Ir(ppy)3 in the presence of sodium
acetate, were found to be the most optimal conditions. In total 23 differently substituted
indoloazepinone analogues were synthesised with yields up to 85% .
Date of Award3 Oct 2023
Original languageEnglish
Awarding Institution
  • University of Bristol
SupervisorVarinder K Aggarwal (Supervisor), Chris L Willis (Supervisor) & Kevin I Booker-Milburn (Supervisor)

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