Stereoselective Synthesis of Atropisomeric Fluorophores for Asymmetric Photocatalysis

Project Information

AtropFluoPhoto

Grant agreement ID: 840456

DOI

10.3030/840456

Project closed

EC signature date 10 April 2019

Start date 1 May 2019

End date 30 April 2021

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 203 149,44

EU contribution

€ 203 149,44

Coordinated by

UNIVERSITAT BASEL
Switzerland

Periodic Reporting for period 1 - AtropFluoPhoto (Stereoselective Synthesis of Atropisomeric Fluorophores for Asymmetric Photocatalysis)

Reporting period: 2019-05-01 to 2021-04-30

Summary of the context and overall objectives of the project

Manufacturing has regained its strategic significance as a key component of modern economy in recent years worldwide. In Europe, the pharmaceutical and chemical industries make up a substantial share of the gross domestic product (GDP).(1) For a sustainable production, a new generation of chemical synthetic technologies must be developed for the advanced manufacturing of pharmaceuticals and other high value chemicals. In this context, one of the current challenges is to develop green and innovative catalysis approaches to selectively access optically enriched functional molecules. The proposed research hence aims to explore asymmetric catalysis that will allow for novel and cost-effective protocols for the rapid construction of chiral heterocyclic fluorophores.
In view of these, with the generous support of MSCA-IF (Project ID: 840456) from European Commission, Dr. Xingxing Wu has conducted two-year postdoctoral research under the supervision of Prof. Christof Sparr in Department of Chemistry, University of Basel, attempting to challenge the above issue by developing stereoselective control strategy for atropisomeric acridinium fluorophore synthesis.
The acridiniums are particularly useful scaffolds in numerous fields, such as probes, bioimaging, and design of dynamic supramolecular systems.(2) Recently, the 9-arylated acridinium fluorophores, have been demonstrated by Fukuzumi and Nicewicz to be very powerful visible light photocatalysts due to their remarkable redox properties.(3,4) The general acridiniums, as well as other xanthene dyes, are typically symmetric and do not allow stereoinduction. Given the fact that axially chiral (hetero)aryl-(hetero)aryl compounds are broadly applicable in stereoselective catalysis serving either as catalysts or ligands,(5) in this contribution, we develop a stereoselective method to prepare atropoisomeric acridinium fluorophores with a stereogenic axis for the first time. This study would lead to the significant understanding on the axially chiral fluorophore system which has rarely been explored before.

1 CIA World Factbook. last updated on January 20, 2018.
2 Y.-C. Lin, C.-T. Chen, Org. Lett. 2009, 11, 4858.
3 N. A. Romero, D. A. Nicewicz, Chem. Rev. 2016, 116, 10075.
4 A. Tlili, S. Lakhdar, Angew. Chem. Int. Ed. 2021, doi: 10.1002/anie.202102262.
5 J. Clayden, W. J. Moran, P. J. Edwards, S. R. LaPlante, Angew. Chem. Int. Ed. 2009, 48, 6398.

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

In the past two years, Xingxing Wu has been fully engaged to develop innovative catalytic strategy for asymmetric synthesis of chiral heterocyclic fluorophores bearing a stereogenic axis. Under the supervision of Prof. Dr. Sparr and after extensive studies, the researcher has identified a direct cation-promoted Friedel-Crafts type cyclization and cascade oxidation sequence to access atropoisomeric acridinium fluorophores. The key point for success of this methodology relies on the use of chiral disulfonimide catalyst (DSI) with the reactive triaryl imidate precursors. A ion-paring intermediate between the generated cation from the substrate and chiral anion from DSI catalyst was proposed for the enantioselective control.
With the developed approach, various atropoisomeric fluorophores were obtained in high yields and enantioselectivities under mild conditions. To demonstrate the utility of the prepared acridiniums in chemical synthesis of advanced functional molecules, a late-stage diversification of Cl-substituted acridiniums was successfully achieved via a nucleophilic aromatic substitution pathway. This application renders a direct way for structural modification with distinct modularity of acridinium salts featuring diverse photophysical properties. Furthermore, unique chemical, physical and photochemical properties were observed from the established acridinium library, which may allow for practical applications in various areas. These interesting results are now in preparation for submission to a high impact chemistry journal and will be open access after publication.

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)

From the point of academic research, the project demonstrates a Brønsted acid catalyzed Friedel-Crafts type cyclization to access axially chiral acridiniums, presenting the first example on the catalytic atroposelective synthesis of heterocyclic fluorophores. The obtained chiral functional fluorophores can be expected to provide a unique solution to the long-standing challenge of enantioselective photochemical transformations. In addition, the proposed study shall bring the academic attention to novel atropisomeric fluorophore scaffolds, which may find potential utilization in a broad range of scientific areas, such as bioimaging and enantioselective recognition in biological systems.

Acknowledgement: Dr. Xingxing Wu sincerely thanks the support from MSCA-IF (Project ID: 840456), University of Basel, as well as the generous help from the whole Sparr group.

Overview of the research work

State-of-art of the project