Metal-Free Cross-Coupling Reactions Enabled by Sulfonium Salt Intermediates

  • Mindaugas Siauciulis

Student thesis: Phd


The formation of carbon-carbon bonds is arguably one of the most important tasks in organic chemistry and is key for the efficient construction of molecular scaffolds. The advent of transition-metal-catalyzed reactions has vastly expanded the toolbox of synthetic organic chemists and facilitated the development of otherwise extremely challenging chemistries. Such reactions usually make use of platinum-group metal catalysts, which, despite their unique reactivity, pose several risks, including potential residual toxic contamination of final chemical products, depletion of raw precursors, and costliness of development. Main-group chemistry has long been investigated as an alternative and complementary approach to the use of transition-metal-catalyzed reactions. Recently, the Procter group has reported several transition-metal-free carbon-carbon bond forming processes enabled by sulfur-based intermediates. In particular, sulfonium salts, conveniently accessed via an interrupted Pummerer process from simple, non-prefunctionalized coupling partners, have been shown to be versatile synthetic intermediates, enabling a variety of carbon-carbon bond forming processes. Herein, further investigations into the expansion of such methodologies are reported. Key sulfonium salt intermediates, depending on the nature of substrates and reaction conditions, are processed in a variety of ways, enabling novel cascade procedures: (I) Rearrangements of intermediate sulfonium salts allow highly efficient dual vicinal functionalization of heterocyclic coupling partners. A mild, general, and convenient sulfenylation/rearrangement protocol delivers biologically-relevant, functionalised heterocycles. (II) Reaction of intermediate sulfonium salts with organometallic reagents allows access to largely unexplored sulfurane intermediates, which are prone to ligand-coupling reactions. A highly selective coupling procedure was applied to the stereoselective synthesis of dienes and substituted biaryls. (III) Photoredox-catalysed cross-coupling of aryl sulfonium salts with arenes and heteroarenes allows facile access to valuable (hetero)biaryl motifs. The new methodology was applied to the synthesis of a natural product, pentachloropseudilin, and an unnatural analogue.
Date of Award31 Dec 2020
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorDavid Procter (Supervisor)


  • sulfoxide
  • cross-coupling
  • sulfonium salt
  • Pummerer

Cite this