Adapting polymerisation techniques for small molecule synthesis

Abstract

Atom transfer radical polymerisation (ATRP) is an industrially important methodology for controlled radical polymerisation. Copper catalysed ATRP remains the most developed variant, with advancements enabling air tolerance and ppm-level catalyst loadings. At its core ATRP depends upon a mediator complex to reversibly generate the propagating radical. In this thesis, we bridge the gap between atom transfer radical polymerisation and small molecule synthesis; by strategically applying ATRP mediators and methodology to cross-coupling chemistry. First, via the development of a copper-catalysed C-N bond cross-coupling, using a cheap and accessible ATRP mediator. Followed by the introduction air tolerance into Cadiot-Chodkiewicz and Sonogashira cross couplings via the introduction of sodium ascorbate and ascorbic acid. Finally, we attempt to extend the scope of ATRP through the development of a model synthesis towards new generation of capped ATRP ligands Previously computationally evaluated to be far more active than the current generation of ATRP mediators. Together these developments further connects ATRP to small molecule synthesis, highlighting the generalisability of ATRP methodology. Furthermore, significant progress has been made towards a new generation of ATRP catalysts.