Catalytic synthesis and modification of heterocycles

  • William Mahy

Student thesis: Doctoral ThesisPhD


The following thesis outlines work carried out during the past three years for the discovery and investigation of catalytic methodologies towards the synthesis and modification of heterocycles, namely cyclic carbamates, carbonates and their sulfur analogues.Chapter 1 summarises the current catalytic methods reported in the literature towards the synthesis and modification of functionalized 2-oxazolidinones. This introduction highlights the diverse range of methods and catalysts that have been developed and their scope and limitations. In addition the review highlights the importance of these structural motifs and suggests areas in which the following research fulfills unmet needs.Chapter 2 reports the discovery and development of a one-pot two-step copper-catalysed methodology towards the synthesis of N-aryl oxazolidinones from amino alcohol carbamates. The scope of both the N-aryl substituent as well as oxazolidinone functionalization is presented in addition to preliminary investigations into the mechanisms of both reactions.Chapter 3 presents the application of the previously reported one-pot process towards the synthesis of a number of medicinally active molecules and blockbuster pharmaceuticals. The one-pot two-step copper-catalysed reaction was utilized to synthesise a common intermediate in the synthesis of a number of oxazolidinone-based pharmaceuticals. The complete syntheses of Toloxatone, Linezolid, Tedizolid and Rivaroxaban are reported.Chapter 4 reports the modification of N-aryl oxazolidinones towards a diverse library of N-aryl oxazolidinethiones. The reactivity of these structures, in addition to N-alkyl oxazolidinethiones, towards transition metal catalysis was investigated and revealed a ruthenium catalysed O- to S-alkyl migration to afford structurally diverse thiazolidinones. Investigations into the substrate scope and mechanism were also carried out, suggesting a pseudo-reversible radical pathway drawing mechanistic parallels to the classic Barton-McCombie reaction.Chapter 5 details further development of the pseudo-reversible radical pathway for the regioselective rearrangement of dioxolane-2-thiones using Pd(PPh3)4 as a catalyst. The scope of the reaction is reported for the formation of highly selective, highly substituted sulfur-rearrangement products.
Date of Award18 Feb 2016
Original languageEnglish
Awarding Institution
  • University of Bath
SupervisorChristopher Frost (Supervisor) & Pawel Plucinski (Supervisor)


  • catalytic
  • heterocycles
  • copper
  • ruthenium
  • radical
  • rearrangement

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