Lifestyle behaviours, such as whether we smoke and drink alcohol, how much we eat, and the amount of exercise we take, have a major impact on our health and mental health. This programme will focus on improving our understanding of why people engage in unhealthy behaviours, what the consequences of these behaviours are for our health and mental health, and what we can do to encourage people to live healthier lifestyles. It will draw on a wide range of different techniques, including epidemiology, genetics, epigenetics, laboratory studies and clinical trials. Lifestyle behaviours represent the primary modifiable causes of illness and premature death in developed countries such as the United Kingdom, and anything which improves our understanding of these behaviours has the potential to dramatically improve public health.

Cyclobutanes are common motifs in natural products and are increasingly important in medicinal chemistry since they can orient substituents along precise vectors. However, methods to construct cyclobutanes are less developed in comparison to their smaller and larger rings. Consequently, novel methods to access functionalized cyclobutanes are highly desirable and would be of considerable value for the discovery of new bioactive compounds. In the last decade, the host group and others have contributed significantly to the development of boron 1,2-migration chemistry which has found numerous applications in organic synthesis. Normally, 1,2-metallate shifts in boronate complexes are induced by α-leaving groups or by reactions of alkenyl boronates with halogens, π-acidic metals, or radicals. Herein, we are proposing a fundamentally new strategy to induce 1,2-metallate rearrangement, via a ring expansion of vinyl cyclopropyl boronate complex activated by an electrophile or by photoredox or transition metal catalysis. This novel process would lead to highly versatile boronic ester containing cyclobutanes, which can be transformed into other valuable functional groups. Furthermore, we plan to use chiral ligands in combination with palladium catalysis in this novel process, leading to enantioenriched chiral cyclobutyl boronic esters. These novel methodologies not only benefit from the formation of highly functionalized cyclobutanes, but also lay solid foundations for the development of other ring-expansion induced 1,2-metallate rearrangements. The scope of these processes will be carefully investigated, and mechanistic studies of the photoreaction will be carried out using advanced physical/chemical methods. Finally, this project will enable significant knowledge transfer between the host and researcher, while forging new academic networks within the scientific community.

The CDT PhD Project will start in the second year of the programme, Sept 2020