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

Programme(s): H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility

Topic(s): MSCA-IF-2019 - Individual Fellowships

Call for proposal: H2020-MSCA-IF-2019

Funding Scheme: MSCA-IF-EF-ST - Standard EF

Grant agreement ID: 890680

Project description:

Uncommon nucleophiles could advance the field of asymmetric Suzuki reactions

A Suzuki reaction provides a simple route to creating carbon-carbon bonds to form compounds that can serve as the starting points for synthesising a variety of organic bioactive compounds. In this palladium-catalysed reaction, the coupling partners are an electrophile, usually an organohalide, and a nucleophile, usually a boronic acid. The EU-funded BISBORONDYKAT project plans to develop a general cross-coupling procedure that will effectively allow the use of 1,1-bis(boryl)alkanes in asymmetric Suzuki reactions. To achieve this transformation, it will use the dynamic kinetic asymmetric transformation protocol recently developed by the research group. The new method could lead to new advances in asymmetric cross-coupling reactions, with important implications for the development of new drugs.

Objective:

Suzuki−Miyaura coupling (SMC) has emerged as a powerful strategy in the field of cross-coupling reactions and is widely used in synthetic organic chemistry and drug development. Asymmetric SMC reactions employing aryl/alkenyl boronic acid is well developed; however, no general Csp3 – Csp3 Suzuki-Miyaura coupling is currently available. Furthermore, the asymmetric addition of benzylic nucleophile or 1,1-difunctionalized reagents as a nucleophile is quite rare.

This proposal aims to develop a general cross-coupling procedure that will effectively allow the use of 1,1-bisboryl alkanes in asymmetric SMC reactions. We intend to utilise the rhodium and copper catalysed dynamic kinetic asymmetric transformations (DYKAT) protocol developed in the Fletcher group to achieve this transformation. The corresponding enantioenriched product would feature boronic ester moiety equipped for further modification. Furthermore, the transformation would serve as an alternative protocol for the addition of difficult to install benzylic group. The method would provide a significant advancement in asymmetric cross-coupling reactions and would fortify the broad applicability of DYKATs in SMC reactions in the field of synthesis, medicinal and materials chemistry.