Regioselective Hydrogen Bonding Phase Transfer Catalysis

Informazioni relative al progetto

REGIOFLU

ID dell’accordo di sovvenzione: 890535

DOI

10.3030/890535

Progetto concluso il 23 Febbraio 2021

Data della firma CE 5 Marzo 2020

Data di avvio 1 Aprile 2020

Data di completamento 31 Marzo 2022

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 212 933,76

Contributo UE

€ 212 933,76

Coordinato da

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

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

Periodo di rendicontazione: 2020-04-01 al 2022-03-31

Sintesi del contesto e degli obiettivi generali del progetto

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.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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.