NewBorN · Unveiling new B-, N- containing structures through photoredox catalysis
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-07-31 → 2020-07-30
- EU contribution
- €195,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Unveiling new B-, N- containing structures through photoredox catalysis
The main original objective of the project was the construction of new B-, N-containing structures via photo-induced 1,2-migration of boronate ate complex, which would open significant opportunities in synthesis of biological compounds. Building upon the boronate complex radical reactivity reported recently, we propose to generate N-centred radicals through photoredox catalysis, and trap them with vinyl boronate complexes. The methodology will lead to a novel three component coupling where new C-C and C-N bonds are formed in one-pot, providing a new synthetic avenue for the preparation of β-amino boronic esters. These novel methodologies benefit from the formation of highly functionalized products bearing synthetically versatile boronic ester moieties. Furthermore, amino boronic esters or boronic acids have been demonstrated to act as peptidomimetics. Specifically, β-amino boronic acids have shown significant antibacterial activity against Mycobacterium tuberculosis. In the modified plan, we also developed new methodology for the transformation of [1.1.1]propellane. [1.1.1]propellane is the most important starting material for quick access to functionalized bicyclo[1.1.1]pentanes (BCPs) which are highly valuable surrogates of aromatic rings in drug discovery for their more favorable pharmacokinetic properties, including improved aqueous solubility, increased membrane permeability, and higher metabolic stability. Therefore, exploring novel strategies to synthesize diverse 1,3-bifunctionalized BCPs is of great significance in drug evolution. Finally, using [1.1.1]propellane as readily available stuff, we realised the efficient synthesis of divergent functionalized BCPs including alkenyl-, alkyl-, and aryl-BCP derivatives, tertiary boronic ester substituted BCPs, and highly functionalized α-chiral BCPs, which are not accessible by classical strategies. Moreover, we have also developed a new approach to methylenespiro[2.3]-hexane derivatives via a nickel-catalyzed cyclopropanation of alkenes with [1.1.1]propellane. This nickel-catalyzed process unveils a new reaction mode that will enhance the application of [1.1.1]propellane in the synthesis of complex molecules.
Data: CORDIS, © European Union
Project objective
In the past decade, photoredox catalysis has emerged as a tremendously versatile process to generate reactive radical species in organic synthesis under very mild conditions. Meanwhile, the host group have developed a suite of transformations exploiting the fundamental chemistry of boron, many of which involve 1,2-metallate rearrangement of boronate complexes. In this proposal, we propose to merge the N-centred radicals generated through photoredox catalysis and 1,2-metallate rearrangements of vinyl boronate complexes to create an efficient new strategy for organic synthesis, which will lead to a novel three component reaction where new C–C and C–N bonds are formed in one-pot, providing a new synthetic avenue for the preparation of β-amino boronic esters. Moreover, intramolecular radical cyclizations followed by oxidative 1,2-migration will enable the stereoselective synthesis of diversely functionalized cyclic amines. The scope of these processes will be carefully investigated, and mechanistic studies will be carried out using advanced physical/chemical methods. These novel methodologies not only benefit from the formation of highly functionalized products bearing both synthetically versatile boronic ester and amino moieties, but also lay solid foundations for the development of this new field. Based on the significant antibacterial activity against Mycobacterium tuberculosis of β-amino boronic acids, a preliminary test of the biological activities of compounds obtained throughout the proposed research (both cyclic and linear β-amino-boronic acids) will be carried out in collaboration with AstraZeneca. By combining two major fields of endeavour, new chemistry will emerge with unique structures harbouring novel properties for exploitation. Furthermore this project will enable significant knowledge transfer between 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