RACING · Rapid access to functionalized cyclobutanes via ring expansion strategies
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-04-01 → 2021-06-11
- EU contribution
- €224,934
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Rapid access to functionalized cyclobutanes via ring expansion strategies
We are highly grateful to Marie-Curie Actions for enabling us to establish fundamentally a new method to trigger 1,2-metalate rearrangements of boronate complexes. This process affords cyclobutyl boronic esters with high levels of diastereoselectivity. The following project objectives were correctly achieved. 1. Synthesis of vinyl cyclopropyl boronate complexes 2. Realization of ring expansion-induced 1,2-metalate rearrangement using photoredox methods 3. Development of asymmetric palladium-catalyzed ring expansion-induced 1,2-metalate rearrangements. Overall, the developed methodology not only benefits from the formation of highly functionalized cyclobutanes, but also lays a solid foundation for the development of other ring-expansion induced 1,2-metalate rearrangements. The discoveries are expected to significantly impact the chemical and the pharmaceutical industry introducing new avenues to synthesize previously inaccessible compounds. As a result of the career development enabled by this fellowship, the Fellow secured an academic position in one of the renowned Universities in India (IISc Bangalore), and he started his academic career in May 2021.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- UNIVERSITY OF BRISTOL · BRISTOLCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union