DS03 - Stimuler le renouveau industriel

A Sustainable Cooperative Catalysis for the Introduction of SRf groups by C-H functionalization – SCoopCH

A Sustainable Cooperative Catalysis for the Introduction of SRf groups by C-H functionalization

The design of new and sustainable approaches to builp up fluorinated molecules from simple building blocks is a real challenge for our society. In particular, more eco-compatible solutions based on a cooperative catalysis for the transition metal-catalyzed functionalization of molecules by C-H bond activation will be developed in the SCoopCH project to access SRf-containing compounds of interest.

Development of sustainable transformations by cooperative catalysis to access SRf-containing molecules

The SCoopCH project aims at designing new and sustainable approaches for the transition metal-catalyzed functionalization of aromatic and aliphatic derivatives with various SRf groups (SCF3, SCF2H and SCF2FG) by C-H bond activation. To reach that challenging goal, we intend to bring eco-friendly solutions based on a cooperative catalysis. Proposed methodologies combining original C-H bond functionalization with a focus on cost-efficient first row TMs and new strategies to generate SRf sources, will be disclosed. The ultimate goal of the SCoopCH project is to access new SRf-containing molecules inaccessible so far. These technologies will offer new synthetic routes in agreement with environmental concerns. In consequence, this project will have a strong impact in pharmaceutical and agrochemical industries, opening new perspectives for the potential industrial applications of C-H bond transformations.

Transformations using cooperative catalysis as an efficient tool will be developed in the SCoopCH project for the transition metal catalyzed direct functionalization of C(sp2) and C(sp3) centers with SRf moieties. Hence, the project will be organized in two tasks. Task 1 will focus on the functionalization of derivatives using readily available sulfur and nucleophilic Rf sources via a bimetallic catalysis. A long standing goal is to get a straightforward tool for the direct introduction of various SRf residues. Task 2 will focus on the in situ generation of an electrophilic SRf source in a catalytic fashion for the TM-catalyzed C-H bond functionalization reaction of molecules. Due to the exploratory character of this strategy, a progressive organization of task 2 will ensure the feasibility of the approach: 1) validation of the C-H activation step with a stoichiometric SRf electrophilic source (task 2.1) then 2) evaluation of the cooperative catalysis (task 2.2).

Over the last eighteen months, a PhD student was recruited for the SCoopCH project and was involved in the design of a new transformation to access SRf-containing molecules via the in situ generation of the SRf source in a catalytic fashion (Task 2). Taking into consideration the difficulty to tackle this synthetic challenge, a stepwise approach was privileged. In this perspective, studies to determine the best reaction conditions to get a general approach towards the transition metal trifluoromethylthiolation reaction of unsaturated molecules by C-H bond activation was undertaken at first. The amide derived from the 8-aminoquinoline and analogs turned out to be privileged bidentate directing groups for this Pd-catalyzed reaction and the use of the Munavalli reagent was also crucial. All the collected data combined with the expertise acquired by the PhD student will be an asset for the follow-up of our investigations. This work already led to a publication in European Journal of Organic Chemistry in 2018. Besides, by studying the introduction of a SR group on a C(sp2) center by transition metal catalyzed C-H bond activation, an unexpected result was obtained. The synthesis of a panel of original and highly value-added heterocycles was achieved, these derivatives being of high interest for medicinal chemistry. We are currently studying this new transformation and this work should be published in the coming months.

Several synthetic issues will be tackled in the coming months in agreement with the provisional program.
Investigations from the PhD student on the design of a new transformation to access SRf-containing molecules via the in situ generation of the SRf source in a catalytic fashion will be undertaken thanks to the knowledge acquired over the first months.
The current work on the synthesis of original and highly-value added small heterocycles will be continued and finalized in the coming months.
Finally, as initially planned, task 1 will be studied by the newly recruited post-doctoral researcher.

« Pd-Catalyzed Trifluoromethylthiolation of Unsaturated Compounds: A General Approach » Q. Zhao, M.-Y. Chen, T. Poisson, X. Pannecoucke, J.-P. Bouillon, T. Besset
Eur. J. Org. Chem. 2018, 6167.

The SCoopCH project belongs to the “Major Societal Challenges” defined by the ANR agency. In a society in which the saving energy and the ecological debt are two of the major concerns, it is urgent to mobilize research and innovation forces to develop a “greener chemistry”. The growing awareness of the need to reduce the amount of waste and the number of synthetic steps aroused the interest of the chemist community to elaborate sustainable transformations and new retrosynthetic disconnections based on the principles of “eco-design”. Therefore, as part of the strategies developed by chemists, the direct functionalization of a C-H bond is a promising tool offering unprecedented disconnections, which fulfills the criteria of atom- and step-economy. Besides, due to the impressive ability of the fluorine atom and fluorinated groups to alter the biological and physical properties of molecules, the organofluorine chemistry is a research field of tremendous importance in materials as well as pharmaceutical and agrochemical industries.

The SCoopCH project aims at designing new and sustainable approaches for the transition metal-catalyzed functionalization of aromatic and aliphatic derivatives with various SRf groups (SCF3, SCF2H and SCF2FG) by C-H bond activation. To reach that challenging goal, we intend to bring eco-friendly solutions based on a cooperative catalysis. Proposed methodologies combining original C-H bond functionalization with a focus on cost-efficient first row TMs and new strategies to generate SRf sources, will be disclosed. The ultimate goal of the SCoopCH project is to access new SRf-containing molecules inaccessible so far. These technologies will offer new synthetic routes in agreement with environmental concerns (to minimize the production of waste and atom- and step-economical reactions). In consequence, this project will have a strong impact in pharmaceutical and agrochemical industries, opening new perspectives for the potential industrial applications of C-H bond transformations.

Project coordinator

Madame Tatiana Besset (laboratoire COBRA)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

laboratoire COBRA

Help of the ANR 240,840 euros
Beginning and duration of the scientific project: September 2017 - 48 Months

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