The reactivity of strained carbocycles

Thesis

The idea that increasing a reaction driving force will increase its rate is a central principle of chemistry. This principle has been used to great effect for the design of ‘strain-release’ reactions, in which a driving force is provided by building strain energy into the reactant. However, strain release alone is unable to account for the contrasting reactivity of even the simplest of systems, such as cyclopropane and cyclobutane which release near-identical amounts of strain energies but display stark differences in their rates of ring-opening. In this Thesis, the dominance of strain release is challenged by introducing the concept of electronic delocalisation to enhance reactivity: a more delocalised bond will be easier to break, and therefore incur a lower activation barrier to its cleavage resulting in a faster reaction rate. This idea is first explored through a computational study of the electronic structure and reactivity of [1.1.1]propellane (Chapter 2), before the importance of delocalisation is explored in the development of a new synthesis of alpha-chiral bicyclo[1.1.1]pentanes – important motifs in drug discovery (Chapter 3). The relationship between reaction rate, strain release and delocalisation is then quantified through the development of a predictive model for the reactivity of small rings in general (Chapter 4), where three-membered rings are found to be unique in their ability to cause delocalisation-enabled reactivity. In summary, this Thesis introduces a framework to better understand the relationship between ring strain and reactivity, and in doing so guide synthetic efforts towards new reaction design.

Authors: Sterling, AJ

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: reactivity; strain; electronic structure; chemistry
• Subjects: Reaction mechanisms (Chemistry); Chemistry