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Palladium catalysed functionalisation of heterocycles

  • Dan E Giernalczyk

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

Palladium catalysed transformations provide an indispensable tool for the preparation of intermediates for use in natural product synthesis including, for example, the assembly of complex polyheterocycles. This thesis describes two main areas focussed on palladium catalysis; Pd(0)- catalysed allylic cyclisations and Pd(II)-catalysed C-3 directed C–H activation of furan substrates. An overview of both Pd(0) and Pd(II) catalysis is described in Chapter 1.
The long term aim was to use Pd(0)-catalysed allylic cyclisations in the total synthesis of bisdehydroneotuberostemonine. Studies began with investigations on a Pd(0)-catalysed cascade sequence using an unsaturated diacetate, to form the stenine core of the natural product. However, the required reactions proved challenging, so alternative substrates were designed and synthesised for further studies on the key cyclisation, but this remained elusive.
Next, intermolecular reactions with unsaturated esters were investigated with the aim of developing an efficient method of C-3 directed Pd(II)-catalysed C–H activation for furans bearing an amide directing group. A series of substituted furans was prepared and following initial C-H activation studies, optimisation of the reaction was achieved by a combination of traditional reactant screening and a Design of Experiments (DoE). Whilst this led to a significantly improved yield (8% to 39%), the scope of the reaction remained limited in terms of the structure of the furan with four derivatives giving the required coupling.
Date of Award25 Jan 2022
Original languageEnglish
Awarding Institution
  • University of Bristol
SupervisorChris L Willis (Supervisor) & Kevin I Booker-Milburn (Supervisor)

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