The arylation of 2-pyrones and related heterocycles
Prendergast, Aisling M.
University College Cork
2-Pyrones, and related heterocycles such as 2-pyridones, 2-coumarins and 2- quinolones, are useful model substrates to test a novel methodology due to their varied chemical properties. In addition, these moieties possess broad spectrum biological activity. Chapter 1 provides a review of C–H activation methodology as it has been applied to 2-pyrones and related heterocycles. Direct arylation via C–H activation of 2-pyrone, 2-pyridone and 2-coumarin compounds is described in Chapter 2. Protocols for the palladium-catalysed direct arylation of these molecules were developed and applied to a library of substrates. C–H activation at both the C–3 and C–5 positions of the 2-pyrone scaffold was achieved. The C–5 direct arylation methodology proceeded with retention of a C–Cl bond to give a cyclised 3-chloro-2-pyrone. In Chapter 3, the development of cross-coupling conditions for the cyclised 3-chloro-2-pyrone is discussed. Following on from this, more generally applicable, environmentally friendly cross-coupling conditions evolved to allow the application of green chemistry principles to the Suzuki-Miyaura cross-coupling of 2-coumarins, 2-pyrones, 2-pyridones and 2-quinolones, with yields of up to 99%. In parallel to the synthetic aspects of this project, investigations were also performed to understand the mechanisms through which 2-coumarins and related heterocycles undergo C–H activation and direct arylation reactions. In Chapter 4 the experiments which were performed as part of these investigations are described, and the results are presented. Based upon these results from three different sets of reaction conditions, it was proposed that C–H activation of these substrates occurs via concerted metallation-deprotonation.
2-pyrones , 2-pyridones , 2-quinolones , C-H activation , Suzuki-Miyaura , Organic chemistry , Direct arylation , Coumarins
Prendergast, A. M. 2018. The arylation of 2-pyrones and related heterocycles. PhD Thesis, University College Cork.