Periodic Reporting for period 1 - FUSE (Dual Co/Photoredox Catalysis for the Synthesis of Fluorine-Containing Skipped Dienes Featuring a Quaternary Carbon Stereocenter)
Reporting period: 2022-06-15 to 2024-06-14
The FUSE project has targeted a chemical methodology development, which set the stage for the synthesis of new type fluorinated molecular building blocks with importance in life sciences due to their diverse reactivity, versatile distribution in pharmaceutically active structures. The investigation is addressing also serious issues of sustainability. Notably, in contrast to the traditional chemical approaches which involve the non-sustainable use of large amount and hazardous reducing agents, photoredox catalysis has recently emerged as a new and effective tool allowing to produce the new fluorinated compounds needed in an environmentally benign way. Despite the critical relevance of fluorine atom incorporation into organic molecules, the synthetical implementation is still challenge. Attractively, FUSE offers the exploitation of simple hydrofluoroolefins (HFOs) present an excellent opportunity to introduce fluorinated motifs into drug precursors. HFOs primarily used as 4th generation refrigerants with low atmospheric lifetime/global warming potential, and zero ozone depletion potential, and for this reason these feedstock chemicals are produced on large scale and easily accessible, however, there are only scarce examples discussing their utilization.
As the FUSE project has generally targeted a methodology development, it has significant impact on the scientific society by broadening the chemical knowledge space. In this frame, the new HFO conversions can undoubtedly boost the wider applications of these feedstock chemicals, opening new possibilities for the synthesis of fluorine-containing precursors. The application of visible light photocatalysis allows the researchers and scientists to perform reactions under milder reaction conditions, avoiding dangerous or highly toxic chemicals. The development of a more environmental-friendly methodology facilitates the further possible industrial implementations, reducing the amount of hazardous materials and chemical waste. This project targeted to access to new fluorinated molecular building blocks in a shorter synthetic route, which was difficult to prepare before. In wider context, the produced organic chemical compounds may provide an impetus for new medicinal and agrochemical applications while the new ideas and methodology help scientist to understand better certain reaction mechanisms fostering the further expansion of this chemical research. In general, the technological development is essential for the modern society, which relies heavily on chemical research. In order to face the natural and societal challenges there is a continuous need for new knowledge and cutting-edge approaches. Besides the multidisciplinary research development this project arise interest in science, promote forward-looking thinking and encourage the next generations to study chemistry.
FUSE has set the stage for the development of novel fluorine-containing skipped dienes bearing a stereodefined quaternary carbon centre. Beyond the preparation of industrially relevant fluorinated compounds, by this methodological advancement new reactivity centered around the use of electron-deficient HFOs has been explored using carbon-based nucleophiles prepared via photoredox-controlled ‘Umpolung’ reduction of electrophilic allyl carbonates.
The FUSE project is divided into two specific objectives (SOs):
SO1: Generation of low-valent Co-allyl complexes by photocatalysis and their coupling with HFOs
SO2: Fine-tuning of the chiral environment around the Co center to induce asymmetric induction
As the FUSE project has generally targeted a methodology development, it has significant impact on the scientific society by broadening the chemical knowledge space. In this frame, the new HFO conversions can undoubtedly boost the wider applications of these feedstock chemicals, opening new possibilities for the synthesis of fluorine-containing precursors. The application of visible light photocatalysis allows the researchers and scientists to perform reactions under milder reaction conditions, avoiding dangerous or highly toxic chemicals. The development of a more environmental-friendly methodology facilitates the further possible industrial implementations, reducing the amount of hazardous materials and chemical waste. This project targeted to access to new fluorinated molecular building blocks in a shorter synthetic route, which was difficult to prepare before. In wider context, the produced organic chemical compounds may provide an impetus for new medicinal and agrochemical applications while the new ideas and methodology help scientist to understand better certain reaction mechanisms fostering the further expansion of this chemical research. In general, the technological development is essential for the modern society, which relies heavily on chemical research. In order to face the natural and societal challenges there is a continuous need for new knowledge and cutting-edge approaches. Besides the multidisciplinary research development this project arise interest in science, promote forward-looking thinking and encourage the next generations to study chemistry.
FUSE has set the stage for the development of novel fluorine-containing skipped dienes bearing a stereodefined quaternary carbon centre. Beyond the preparation of industrially relevant fluorinated compounds, by this methodological advancement new reactivity centered around the use of electron-deficient HFOs has been explored using carbon-based nucleophiles prepared via photoredox-controlled ‘Umpolung’ reduction of electrophilic allyl carbonates.
The FUSE project is divided into two specific objectives (SOs):
SO1: Generation of low-valent Co-allyl complexes by photocatalysis and their coupling with HFOs
SO2: Fine-tuning of the chiral environment around the Co center to induce asymmetric induction
The project yielded several deliverables including the characterization of the synthetized compounds (starting materials such as vinyl cyclic carbonates, alkyne cyclic carbonates and fluoroalkenes, pre-catalysts, Co-complexes, photosensitizers and so on) the description of feasibility and optimization studies on reaction conditions, mechanistic investigations (kinetic studies, deuterium labelling experiments, scope and limitations etc.) and detailed procedures to obtain the desired products and by-products. The documents detail the general information of the used chemicals, the applied analytical methods, instruments, setups, and specific conditions to provide reproducible, and reliable data for chemical investigation. The scientific results from side-threads were published in 2 peer-reviewed journals (research article in Angew. Chem. Int. Ed. and a review in: Acc. Chem. Res.) and major work of the project were communicated orally, presented on poster for scientific communities in 4 international chemical conferences (ACS Meeting 2024, SISOC 2024, ICIQ School, 25th EUCOMC) and discussed on institutional symposiums and seminars (e.g. 26th Conference Fèlix Serratosa, VII PhD & Postdoc Day). Expectedly, from the major scientific discovery of the project 2 more articles will be published this year, which will provide a useful chemical tool for scientist in life sciences.
Overall, FUSE opened a new area of innovative transformations which can be especially interesting for other researchers in the field of catalysis and organic chemistry and potentially can guide users in chemical and pharmaceutical industries. The published articles and novel principles can encourage other chemist to expand the knowledge on this intellectual space. In wider aspects the dissemination target research and innovation community with the general description of the advanced chemical technologies and motivate newer generation in chemical discoveries. As side thread an additional scientific article will be published in high-impact top-tier Q1 chemical journals and a review is in final stage preparations.