Selective Synthesis of Organosilicon Scaffolds

Leonard, Elizabeth and McLaughlin, Mark G (2025) Selective Synthesis of Organosilicon Scaffolds. PhD thesis, Lancaster University.

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Abstract

Chapter 1 outlines the fundamental reactivity of silicon and the resulting synthetic advantages in organic chemistry. It highlights the growing role of silicon-containing motifs in medicinal chemistry while addressing limitations due to restricted access to diverse organosilane building blocks. Particular focus is given to the utility of vinyl and allylsilanes and the ongoing challenges in achieving their regio- and stereoselective synthesis. Chapter 2 details the optimisation of triflimide-catalysed activation of vinylsilanes to achieve the regioselective synthesis of linear allylsilanes from various silyl hydrides. It also examines limitations related to functional group compatibility, catalyst loading, and side reactions. Chapter 3 builds on the work in Chapter 2, employing triflimide-catalysed allylations to synthesise allylsilanes in high regio- and stereoselectivity. It outlines the optimisation process, examines key limitations, and explores the reactivity of the resulting allylsilanes, including attempts to generate allylic alcohols and the successful formation of 1,5-dienes through protodesilylation. Chapter 4 describes the development of a platinum-catalysed hydrosilylation method for the regioselective synthesis of α-silyl-α,β-unsaturated amides. This transformation proceeds with complete regiocontrol, providing access to synthetically valuable silyl-substituted acrylamides. Their reactivity and synthetic potential were also explored. Chapter 5 builds on the work of Chapter 4, further developing hydrosilylation methodology to access β-(E)-silyl acrylamides with high regio- and stereoselectivity. These β-silyl acrylamides complement the previously described vinylsilanes, broadening the structural diversity of accessible silylated amides. Their reactivity and potential applications were also investigated. Chapter 6 presents the overall conclusions and places the research within the wider field of organosilicon chemistry. It emphasizes the importance of regio- and stereoselectivity in allyl and vinylsilane synthesis and highlights the contributions of the developed methods. Finally, it proposes potential directions for future research.