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

Projektinformationen

BISBORONDYKAT

ID Finanzhilfevereinbarung: 890680

DOI

10.3030/890680

Projekt abgeschlossen

EK-Unterschriftsdatum 5 März 2020

Startdatum 3 August 2020

Enddatum 2 August 2022

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten

€ 212 933,76

EU-Beitrag

€ 212 933,76

Koordiniert durch

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)

Berichtszeitraum: 2020-08-03 bis 2022-08-02

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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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