[2+2]-Photocycloaddition Reactions in the Synthesis of Novel Scaffolds and Natural Products

Abstract

[2+2]-Photocycloaddition reactions are a valuable method for the synthesis of cyclobutanes and cyclobutenes, as the basis for complex novel ring-systems, or as intermediates in the synthesis of natural products. This thesis outlines the use of such cycloaddition reactions in two distinct applications; the synthesis of novel tricyclic scaffolds; and a route towards the maleidride natural product, viburspiran. An introduction to photochemistry is given in Chapter 1, followed by specific details pertaining to [2+2]-cycloaddition reactions.
In Chapter 2, a method for the synthesis of fused cyclobutane heterocycles using tandem [2+2]-photocycloaddition and Prins cyclisation reactions is outlined. This modular method allows the transformation of four simple starting materials into complex tricyclic systems. The two-step process offers excellent diastereoselectivity and the products formed contain multiple points for further derivatisation, making them attractive novel scaffolds for drug-like libraries in medicinal chemistry.
Chapter 3 describes the use of [2+2]-cycloadditions for the total synthesis of the core carbocyclic scaffold of maleidride natural product viburspiran. The proposed key step involves an intramolecular de Mayo reaction which upon ring opening, allows synthesis of the bridged cyclooctane structure of viburspiran. A strategy for the completion of the total synthesis has been devised and is currently under investigation.

Date of Award	11 May 2021
Original language	English
Awarding Institution	University of Bristol
Supervisor	Chris L Willis (Supervisor) & Kevin I Booker-Milburn (Supervisor)