Developing ynamide-based transformations for potential use in scaffold synthesis

Hamouche, Laura (2023). Developing ynamide-based transformations for potential use in scaffold synthesis. University of Birmingham. Ph.D.

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Abstract

The nitrogen-heterocyclic motif is an ever-growing source of interest for medicinal and pharmaceutical fields owing to its presence in numerous biologically active structures and medicinally relevant compounds. This thesis describes the development and elaboration of new methodologies suitable as preparative tools to access structurally diverse building blocks containing nitrogen heterocyclic motifs as potential bioactive motifs. The synthesis of complex ynamides and their combination with transition metal catalysts (cobalt, copper, gold) are explored as starting points in the synthesis of highly functionalised azacyclic systems.

This research work discusses the exploration of a cobalt-catalysed polycyclisation sequence that offers rapid access to a range of novel bicyclic aza-cycles from easily prepared ynamides and N-(pivaloyloxy)amides. The substrate scope and limitations of this new method are described as well as its efficiency and robustness. This polycyclisation process shows functional group compatibility across a range of ynamides and N-(pivaloyloxy)amides catalysis precursors through a range of diverse sulfonyl groups and heteroaryl substituents. Post-catalytic transformations deliver new opportunities for diversification on this framework.

A complementary synthetic route was discovered allowing the construction of two structurally unique scaffolds comprising of nitrogen containing heterocycles from related starting materials through selection of a suitable transition metal catalyst (copper or gold). Post-catalytic transformations are explored on these scaffolds, detailing the difficulties encountered due to the complex/reactive nature of these inherent functionality contained within the polycycles.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):