Design and development of halodeboronation methods for organic synthesis

  • Carolina Padovan Frias

Student thesis: Doctoral Thesis

Abstract

Boronic acids and derivatives are one of the most useful classes of compounds in organic synthesis. Methodologies involving diboron systems have emerged recently as a rapid and powerful approach to synthesize complex molecules. Selectivity in these systems is a key aspect and is typically achieved through protecting group strategies. In this approach one boron species is rendered inert under reaction conditions, while the unprotected boron residue can be selectively manipulated. Nonetheless those methods have the drawback of requiring additional actions to allow subsequent functionalisation (such as removal of the protecting group), which limits overall efficiency. However, unprotected diboron systems can undergo a series of equilibria while in solution, which can lead to side reactions and therefore by-products or mixture of products. For instance, inorganic base in reaction mixtures can trigger speciation between the boron compounds, leading to a complex scramble of starting materials and therefore products. The work described in this manuscript investigated the possibility of conducting a chemoselective chlorination, implementing non-protected diboron systems. This would allow the discriminatory functionalisation of boronic acids in the presence of BPin esters, selectively generating an electrophile species in situ. By successfully performing the selective halogenation, the development of the first selective di-nucleophile Suzuki-Miyaura cross-coupling reaction employing two distinct boron species was endeavoured and accomplished. The chemoselectivity in this case could be achieved by a selective activation of boronic acid species over boronic ester in the reaction mixture. The activation of boronic acids approach was then applied to synthesise SPECT imaging agents. The developed technique would provide a metal-free alternative towards the usual metal-catalysed iododeboronation processes.
Date of Award1 Mar 2018
LanguageEnglish
Awarding Institution
  • University Of Strathclyde
SupervisorWilliam Kerr (Supervisor) & (Supervisor)

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