Hetero[3.1.1]propellanes: synthesis and reactivity

Thesis

[n.1.1]Propellanes are compounds containing three rings fused to a central C–C bond, two of which are cyclopropanes. These compounds have become popular because of their diverse ring opening reactions which provide access to bicyclo[n.1.1]alkanes, valuable tools in medicinal chemistry due to their ability to act as bioisosteres for arenes. Arenes are highly abundant motifs in drugs and replacing them with saturated bioisosteres can improve the pharmacokinetic properties of a drug, such as metabolic stability, solubility and lipophilicity. Incorporating heteroatoms into bicyclo[n.1.1]alkanes should further improve the pharmacokinetic properties, however current approaches to such scaffolds have limitations in their scope, practicality and applicability. An ideal approach to access these scaffolds would be via ring-opening reactions of hetero[n.1.1]propellanes as this would allow the late-stage introduction of diverse bridgehead substituents. However, despite decades of research into propellanes made entirely from carbon atoms, heteroatom-containing small-ring propellanes are to date unknown. This thesis presents the first synthesis of a family of hetero[3.1.1]propellanes and demonstrates a range of ring-opening reactions that allow access to diverse hetero-bicyclo[3.1.1]heptanes (hetero-BCHeps).

Authors: Revie, RI

• DOI: 10.5287/ora-yjpvb0opr
• Type of award: DPhil
• Awarding institution: University of Oxford
• Language: English
• Keywords: strained rings; synthesis; bioisosteres; Organic chemistry