Sulfur-Mediated C–H Functionalisation in Arenes and Alkenes Using Low-Cost Metals

  • Miles Aukland

Student thesis: Phd

Abstract

Synthetic advances have equipped chemists with methods to selectively functionalise C-H bonds in organic molecules, thus streamlining syntheses with increased atom economy and more benign by-product generation. Unfortunately, the vast majority of developed processes utilise toxic, platinum-group metals that come from depleting stocks. The need to acquire complementary approaches with cheaper, more abundant and environmentally-friendly first-row transition-metals is well appreciated for this reason. Recently in the Procter group, an iron-mediated oxidative coupling of arenes and alkenes has been developed. Investigations in to the synthesis of pharmaceutically-relevant motifs from the products of these couplings are disclosed. Utilising the synthetic handles present in the coupling products, the synthesis of atypical antipsychotic, dibenzothiepine scaffolds has been achieved. Similarly, elaborate dihydrobenzofuran structures have been accessed using metal-catalysed cross-coupling techniques in a rapid and efficient manner. Efforts towards the development of a more general and catalytic variant of the iron-mediated coupling are also described. Also presented is an efficient protocol for the selective conversion of C-H bonds to C-C bonds using a close alliance of base-metal catalysis and Pummerer-type chemistry that operates under mild conditions; Activated sulfoxides are excellent sulfur electrophiles and can be used to activate arene and alkene C-H bonds. The resulting sulfonium salts serve as pseudohalides in nickel-catalysed cross-coupling reactions with organozinc reagents. The value and power of this developed method is then demonstrated through application to the late-stage modification of complex pharmaceuticals.
Date of Award1 Aug 2018
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorDavid Procter (Supervisor) & Michael Greaney (Supervisor)

Keywords

  • Interrupted Pummerer
  • Nickel Catalysis
  • Sulfur
  • Iron
  • Oxidative coupling
  • Cross-coupling

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