C–C bond activation of strained ring systems

  • Olga Sokolova

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)


Studies towards C-C bond activation-based methodologies involving strained ring systems are presented. The work aims to develop further directing group-assisted cyclisations developed in Bristol. Specifically, aminocyclopropane-based and related ring systems were examined to identify suitable substrates for directed transition metal-catalysed ring cleavage and subsequent
Rare examples of carbonylative rearrangements of aminocyclopropanes using a temporary directing group have been discovered. The process involves an unusual ring contraction and can be used to provide a range of γ-lactams. The method is conceptually unique compared to other temporary directing group strategies used in C-C bond activation.
Investigations into substrates for intramolecular nucleophilic addition to C-C bond activation derived metallacycles identified aminocyclopropanes equipped with anilines as suitable substrates. These cyclopropanes undergo carbonylative cyclisation to form 8-membered Nheterocycles. Studies were also undertaken to evaluate a range of alternative substrates with tethered nucleophiles under carbonylative conditions.
A novel (3+1+2) cycloaddition between aminocyclopropanes, CO and tethered
π-unsaturates has been developed. An extensive study of the reaction scope was undertaken, and conditions for asymmetric cycloadditions were identified. This methodology provides the first examples of highly enantioselective C-C bond activations of aminocyclopropanes.
Additionally, the reactivity of various homologated aminocyclopropanes was investigated. A previously developed carbonylative rearrangement of aminomethylcyclopropanes to α-aminocyclopentanones was re-evaluated. Second-generation conditions were optimised and these offered enhanced efficiencies for certain substrates. The carbonylative rearrangement was
integrated into cascade and tandem processes to access various polycyclic products (e.g. spirocycles and indoles).
Efforts to achieve challenging C-C bond activation-triggered transformations of
aminocyclobutanes are described. Several representative aminocyclobutane-based substrates were evaluated under transition metal-catalysed conditions, but these failed to deliver the desired targets.
Date of Award23 Mar 2021
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorJohn F Bower (Supervisor)


  • C-C Bond Activation
  • Catalysis
  • Asymmetric Synthesis

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