Catalyst Control over X-Fold Stereogenicity

Project Information

X-Fold StereoGen

Grant agreement ID: 101002471

DOI

10.3030/101002471

Project closed

EC signature date 17 December 2020

Start date 1 May 2021

End date 30 April 2026

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 999 266,00

EU contribution

€ 1 999 266,00

Coordinated by

UNIVERSITAT BASEL
Switzerland

Periodic Reporting for period 3 - X-Fold StereoGen (Catalyst Control over X-Fold Stereogenicity)

Reporting period: 2024-05-01 to 2025-10-31

Summary of the context and overall objectives of the project

Stereoisomers are molecules which have the same connectivity, but different arrangements of atoms in space, resulting in distinct properties such as bioactivity. Preparing the desired stereoisomer therefore requires control over the configuration of the groups in the molecule which define stereoisomerism and thus encode molecular topology. Stereoselective catalysis is thereby considered as ideal approach to guide chemical reactions to pathways to give the required stereoisomers. Furthermore, the prospects of minimal side- and byproducts facilitates purifications. While previous catalytic methods were selective for stereogenic units with two configurations, the aim of this EU-funded X-Fold StereoGen project is to catalytically control stereogenic units that encode more than two configurations.

This will allow scientists and ultimately society to catalytically address a larger, nonbinary stereochemical space. The higher-order stereogenic units are controlled with more sustainable synthetic methods to selectively access desired compounds with the required molecular topologies.

The overall objective is to establish the feasibility of catalyst control over higher-order stereogenicity for units with 3-6 configurations. The conceptual relationship between the molecular conformations and higher-order stereogenicity is thereby emphasized. Additionally, the diversity of the increased stereochemical space addressable by catalysis is explored.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The work performed so far allowed to establish the feasibility to catalytically control three-, four- and sixfold stereogenicity. Combinations of two catalysts thereby guided oxidation reactions to form each of the three possible stereoisomers. Furthermore, fourfold stereogenicity was addressed for the synthesis of overcrowded alkenes in a two-step process, while catalyst control over sixfold stereogenicity was rendered feasible by forming an aromatic ring.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Besides rotationally restricted compounds, high-valent stereocenters with more than two configurations were addressed by stereoselective catalysis. We expect that by the end of the project, a diversity of higher-order stereogenic units with three-to-six configurations will become catalytically tractable.

Catalyst control over pentavalent stereocentres