4-π Photocyclisation : a new route to functionalised four-membered rings

Britten, Tom and Coote, Susannah and Kemmitt, Paul (2019) 4-π Photocyclisation : a new route to functionalised four-membered rings. PhD thesis, Lancaster University.

Text (2019BrittenPhD)
ThomasBritten_ThesisFinal.pdf - Published Version
Available under License Creative Commons Attribution-NonCommercial-NoDerivs.
Download (10MB)

Abstract

The work disclosed within this thesis describes the use of photochemistry to develop efficient and scalable methodology to access functionalised four-membered rings. Chapter 2 examines the synthesis and synthetic potential of 1,2-ihydropyridazines. The feasibility of the current literature syntheses of 1,2-dihydropyrdazines on multigram scales has been investigated, which has resulted in the development of a novel, scalable route to unsubstituted 1,2-dihydropyridazines. Currently, the synthesis is not amenable to the synthesis of substituted 1,2-dihydropyridazines. 1,2-Dihydropyridazines are precursors to interesting molecular scaffolds through double bond transformations, however in some cases the isolated product was not the expected product. Chapter 3 investigates the optimisation and scale up of the 4-π photocyclisation of 1,2-dihydropyridazines using commercially available batch and flow photoreactors. The use of a batch photoreactor gave better yields, purity and productivity for the synthesis of bicyclic 1,2-diazetidines compared to the flow photoreactor. The photophysical properties of 1,2-dihydropyridazines have been studied and the data has provided guidance for optimisation and rationale for the observed results. Chapter 4 explores the stability and synthetic potential of bicyclic 1,2-diazetidines to access functionalised 1,2-diazetidines, cyclobutenes and other products that were not expected at the outset of the project. Attempts to access cyclobutenes (through N-N cleavage) were unsuccessful due to a facile 4-π electrocyclic ring opening, whereas it was possible to synthesis a range of novel monocyclic functionalised 1,2-diazetidines. Chapter 5 provides overall conclusions, as well as a comparison of the synthesised compounds to Lipinski’s “rule of five” and lead-like space using open access software and ideas for future work. Chapters 6 and 7 will provide the experimental details and characterisation of novel compounds that have been reported in this thesis. The appendix gives details on the X-ray crystal structures and differential scanning calorimetry traces for a select few examples.