The use of silyl enol ethers as alkene equivalents in the Pauson-Khand Reaction

Student thesis: Doctoral Thesis

Abstract

Over the past two decades, work within our laboratories has focused on the development of the Pauson-Khand reaction to deliver novel methodologies for the construction of flexible cyclopentenone scaffolds. To date, the Pauson-Khand reaction has been widely used to synthesise cyclopentenone motifs in natural product synthesis and beyond. However, there is a distinct lack of examples which use functionalised reacting partners to form diverse cyclopentenones.To address this notable deficiency, we employed, for the first time, silyl enol ethers as alkene equivalents for the intramolecular Pauson-Khand reaction to generate oxygenated cyclopentenones. Using this method, 17 novel cyclopentenones have been synthesised, which feature oxygenation on the cyclopentenone ring. Furthermore, two oxygenated cyclopentenones were readily converted into their fluorinated analogues in one step.In addition to the methodology development, we sought to employ this novel Pauson-Khand reaction in the arena of total synthesis of natural products. In this regard, we selected Xeromphalinone C, a natural product isolated in 2010, which is part of a family of natural products featuring oxygenated cyclopentenone motifs. A novel synthetic sequence to Xeromphalinone C was established, which used our novel Pauson-Khand reaction methodology as a key step, completing the first total synthesis of Xeromphalinone C in 1.6% yield over 16 steps. This highlighted the utility of our novel methodology as a useful step for the synthesis of complex, functionalised cyclopentenone molecules.
Date of Award1 Apr 2020
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorWilliam Kerr (Supervisor) & Glenn Burley (Supervisor)

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