Asymmetric Csp3 – Csp3 Suzuki−Miyaura Coupling Employing 1,1-Bisboryl Alkanes

Informazioni relative al progetto

BISBORONDYKAT

ID dell’accordo di sovvenzione: 890680

DOI

10.3030/890680

Progetto chiuso

Data della firma CE 5 Marzo 2020

Data di avvio 3 Agosto 2020

Data di completamento 2 Agosto 2022

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 212 933,76

Contributo UE

€ 212 933,76

Coordinato da

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom

Periodic Reporting for period 1 - BISBORONDYKAT (Asymmetric Csp3 – Csp3 Suzuki−Miyaura Coupling Employing 1,1-Bisboryl Alkanes)

Periodo di rendicontazione: 2020-08-03 al 2022-08-02

Sintesi del contesto e degli obiettivi generali del progetto

The proposal was aimed to develop new C-C bond forming asymmetric reactions for the synthesis of chemical building blocks. Specifically, we intended to develop new Rh catalysed reactions using commercially available reagents that would provide access to highly versatile enantioenriched products. These methodologies provide access to pharmaceutically relevant molecules and drug candidates that would provide major advancement in the field of synthesis, medicinal and material chemistry.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

The aim of the project was to develop a Csp3 – Csp3 Suzuki-Miyaura coupling employing 1,1’-bisboryl alkanes with racemic allyl halides in asymmetric SMC reactions. We successfully achieved the desired transformation, however, the method had was not broadly applicable. Consequently, we turned
our attention exploring other asymmetric Suzuki-Miyaura coupling reactions.

We discovered a new asymmetric synthetic route towards carbocyclic C-nucleosides, an underexplored class of nucleoside analogues. The methodology featured addition of challenging heterocyclic boronic acids featuring multiple heteroatoms. The addition of nucleobase type boronic acid provides a great progression in SMC coupling reactions. The synthetic route provides access to a chemical space which was previously almost inaccessible. Biological activities of these small molecule are currently under studies and will be reported in due course.

We also realized enantioselective synthesis of dihydropyridines, providing quick access to known drug candidates such as Isoanabasine, Preclamol, Niraparib and PPAR agonists. The method features rhodium catalysed carbometallation in relatively unactivated/strained alkene providing a significant advancement in the field of asymmetric SMC coupling reactions.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

Even though we were unable to achieve a general Csp3 – Csp3 Suzuki-Miyaura coupling employ 1,1’-bisboryl alkanes with racemic allyl halides. We were able to develop multiple methodologies that we anticipate will be widely adopted by synthetic and medicinal chemists.

We try to develop chemistry relevant to current socio-economical needs, for example, our work on the synthesis of carbocyclic C-nucleosides as potent antiviral agent against Cov-SARS-2 was designed and develop during COVID-19 pandemic.

Summary.jpg