Project description DEENESFRITPL Novel method to deliver highly functionalised cyclobutanes Cyclobutanes are common in natural products and are important in medicinal chemistry. Novel methods to access functionalised cyclobutanes will lead to the discovery of new bioactive compounds. Significant progress has recently been made in boron 1,2-migration chemistry with applications in organic synthesis. The EU-funded RACING project is proposing a new strategy to induce 1,2-metallate rearrangement via a ring expansion of a vinyl cyclopropyl boronate complex activated by an electrophile, or by photoredox, or by transition metal catalysis. This will result in versatile boronic ester containing cyclobutanes that could be transformed into other functional groups. The innovation will lay the groundwork for the development of other ring expansion-induced 1,2-metallate rearrangements. Show the project objective Hide the project objective Objective 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. Fields of science medical and health sciencesbasic medicinemedicinal chemistrynatural scienceschemical sciencesinorganic chemistrytransition metalsnatural scienceschemical sciencesinorganic chemistryhalogensnatural scienceschemical sciencescatalysisnatural scienceschemical sciencesinorganic chemistrymetalloids Keywords Cyclobutanes boron chemistry photoredox catalysis perfluoroalkylation palladium catalysis Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator UNIVERSITY OF BRISTOL Net EU contribution € 224 933,76 Address BEACON HOUSE QUEENS ROAD BS8 1QU Bristol United Kingdom See on map Region South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Bristol, City of Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 224 933,76
