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

Información del proyecto

BISBORONDYKAT

Identificador del acuerdo de subvención: 890680

DOI

10.3030/890680

Proyecto cerrado

Fecha de la firma de la CE 5 Marzo 2020

Fecha de inicio 3 Agosto 2020

Fecha de finalización 2 Agosto 2022

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 212 933,76

Aportación de la UE

€ 212 933,76

Coordinado por

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)

Período documentado: 2020-08-03 hasta 2022-08-02

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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.

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