Regioselective Hydrogen Bonding Phase Transfer Catalysis

Project Information

REGIOFLU

Grant agreement ID: 890535

DOI

10.3030/890535

Project terminated on 23 February 2021

EC signature date 5 March 2020

Start date 1 April 2020

End date 31 March 2022

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 212 933,76

EU contribution

€ 212 933,76

Coordinated by

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom

Periodic Reporting for period 1 - REGIOFLU (Regioselective Hydrogen Bonding Phase Transfer Catalysis)

Reporting period: 2020-04-01 to 2022-03-31

Summary of the context and overall objectives of the project

The aim of this project was to develop a paradigm for catalytic regiodivergence in synthetic organic chemistry. This broad objective has been fulfilled in the specific context of nucleophilic fluorination reactions. By utilizing hydrogen bond donor catalysts in this type of reaction, we have shown that the charge on fluoride can be precisely tuned to guide the regiochemical preference of the nucleophile towards a particular site on a reaction partner. Furthermore, this action has enabled us to discover that hydrogen bond donors can activate fluoride as a leaving group, allowing a regioconvergent thermodynamic equilibration process to occur. While the initial proposal aimed at multiple types of substrates (aziridinium ions and metal pi-allyl complexes), we ultimately chose to focus on the biologically relevant case of aziridinium ions, which have led to fluorinated amino acid building blocks through the work enabled by this action. These results will be further exploited by first translating the discovery into a 18Fradiolabelling strategy, which we then intend to use as a handle for functional imaging studies with novel positron emission tomography (PET) probes. This approach to exploitation will present long-term benefits in terms of European research competitiveness in multiple research areas.

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 specific scientific aims of the project were to develop a general approach to catalytic regiodivergence in nucleophilic fluorination (WP1), to apply this approach to regiodivergence in asymmetric catalysis (WP2), and to utilize these advances to access novel radiotracers (WP3). The work that has been carried out has resulted in a successful realization of the aims of WP1, which is in line with the number of person months that have been spent on this action. The training objectives of this project consisted of (i) formulation of a Career Development Plan, (ii) formulation of a Dissemination and Exploitation Plan, and (iii) formulation of a Data Management Plan. Additional training for the beneficiary in the area of radiochemistry was planned if this action had continued, but was not realized due to early termination. The Career Development Plan was written and facilitated meaningful discussions between the beneficiary and the research supervisor, but the other plans were not formally written, although dissemination, exploitation, and data management are all topics of regular discussion between the beneficiary and the research supervisor.

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)

This action has resulted in significant progress in the area of hydrogen bonding phase-transfer catalysis (HBPTC), and more broadly in the field of organocatalysis. The researcher has obtained training in building and maintaining a collaboration with a computational chemist, which will prove vital in preparing him for crossdisciplinary independent research in the future. Knowledge has been transferred from the researcher (who built a research background in asymmetric organocatalysis before this action) to students in the group where this action took place; that knowledge consisted of experimental techniques, fundamental understanding of scientific concepts, and important aspects of publishing and presenting scientific results. On the other hand, knowledge stemming from the group’s background in phase-transfer catalysis has been transferred to the beneficiary, resulting
in a mutually beneficial transfer of knowledge. There were no major difficulties encountered during this process.