Ynones in dearomative spirocyclisation processes; a review

Abstract

This review concentrates on our research into the discovery of novel ynone-based dearomative spirocyclisation processes, whilst placing the new chemistry into the context of existing knowledge. The genesis of the research programme, the development of efficient synthetic routes to prepare the novel natural products spirobacillene A (1) and spirobacillene B (2), utilised the dearomative spirocyclisation of indole ynones. This stimulated a much wider study to explore the reactivity of ynones in dearomative spirocyclisation processes more generally. Routes to generate a wide range of spirocycles were subsequently developed, with dearomative reactions of ynones tethered to indoles, benzofurans, benzisoxazoles, pyrroles, pyridines, isoquinolines, pyrazines, cyclic ketimines, and anisoles all discussed herein, with these reactions initiated by catalytic Ag(I), Cu(II), Pd(0), visible light and many other reagents. Asymmetric variants of some of the reactions are also discussed, as is further elaboration of the spirocyclic products to give carbazoles, quinolones, polycycles and other useful synthetic building blocks. Finally, applications of the new methodology in natural product synthesis (e.g. spirobacillene A, lasubine II and indolizidine 209D) are described.

Keywords

• Indoles
• ynones
• Spirocycles
• Dearomatisation
• Rearrangement