Catalytic Dearomatisation Reactions

This Thesis describes the development of novel catalytic dearomatisation methodologies of indolyl and pyridyl systems for the synthesis of spirocyclic and annulated products. Chapter 1 provides an introduction to this area of research and reviews related reactions, as well as setting out the research objectives.
Chapter 2 describes the cyclisation of indole-alkyne systems I, using Ag(I) or Au(I) catalysis, to selectively form either spirocyclic indolenines III or carbazoles IV in high yield through a common vinyl metal intermediate II. An efficient and reusable heterogeneous catalyst system was also found for the synthesis of indolenines III. A high-yielding asymmetric spirocyclisation methodology was later developed by using the silver salt of a BINOL-derived chiral phosphoric acid V to furnish spirocycles in up to 89:11 er. Finally, these methodologies were applied in brief studies towards the natural product spirobacillene B VI and in an accidental synthesis of actinopolymorphol B VII.
Chapter 3 details the cyclisation of indole α-diazocarbonyls VIII, using Rh(II)-, Pd(II)-, Cu(II)- and SiO2-based catalysts to selectively form 6 different products, namely spirocyclic indolenines IX, oxindoles X and XI, as well as annulated indole isomers XII, XIII and XIV. This work is, to the best of our knowledge, a record number products prepared through catalyst-selective synthesis. A number of diverse mechanistic pathways were proposed in this work, including a surprising reaction involving atmospheric oxygen.
Finally, Chapter 4 describes the cyclisation of pyridine-, pyrazine- and isoquinoline-ynones XV to generate annulated products XVII, which are presumed to form via a vinyl silver species such as XVI. This work ultimately led to a high-yielding 5 step dearomative synthesis of the alkaloid (±)-lasubine II XVIII.