Rapid access to functionalized cyclobutanes via ring expansion strategies

Informations projet

RACING

N° de convention de subvention: 840000

DOI

10.3030/840000

Projet clôturé le 15 Avril 2021

Date de signature de la CE 22 Mars 2019

Date de début 1 Avril 2019

Date de fin 11 Juin 2021

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 224 933,76

Contribution de l’UE

€ 224 933,76

Coordonné par

UNIVERSITY OF BRISTOL
United Kingdom

Periodic Reporting for period 1 - RACING (Rapid access to functionalized cyclobutanes via ring expansion strategies)

Période du rapport: 2019-04-01 au 2021-03-31

Résumé du contexte et des objectifs généraux du projet

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.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The project has completed most of the proposed objectives and milestones within the given period with only a few minor deviations. This project aims to establish new strategies to access versatile boronic esters containing cyclobutanes via ring expansion strategies that would open up significant opportunities in organic synthesis. Vinylcyclopropyl boronic esters are unknown in the literature. In work-page 1, we developed an efficient for synthesizing vinylcyclopropyl boronic esters. In work-package 2, we established a fundamentally new method for accessing cyclobutyl boronic esters with high levels of diastereoselectivity. In work-package 3, we attempted metal-induced 1,2-metalate rearrangement for diasterero/enantioselective synthesis of cyclobutyl boronic esters. Work packages 1 and 2 have been published: Ring-Expansion Induced 1,2-Metalate Rearrangements: Highly Diastereoselective Synthesis of Cyclobutyl Boronic Esters (J. Am. Chem. Soc. 2020, 142, 5515-5520).

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Cyclobutanes are common motifs in natural products and are increasingly important in medicinal chemistry discovery programmes owing to their defined spatial arrangement, a highly desirable feature in drug discovery. The chemistry discovered during this project opened a new chemical space. We believe that this novel methodology lays a solid foundation for the development of other ring expansion induced 1,2-metalate rearrangements to access small rings bearing bioactive compounds. The discoveries are expected to significantly impact the chemical and the pharmaceutical industry introducing new avenues to synthesize previously inaccessible compounds.
This will play a major part in drawing the next generation of outstanding scientists to European institutions, thus increasing the competitiveness of European Science and resulting in long-term benefits for the European economy and the quality of life of all Europeans.

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