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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - FarCatCH (Innovative Strategies for Unprecedented Remote C-H bond Functionalization by Catalysis)

Teaser

Summary

Over the last years, the landscape of the organic chemistry has been reshaped with impressive advances made in the transition metal-catalyzed carbon-hydrogen (C-H) bond functionalization field. Indeed, the functionalization of building blocks that do not display a reactive functional group but only a simple C-H bond is attractive as it avoids time-consuming and expensive prefunctionalization steps and limits the generation of waste. However, as energies required to break C-H bonds are similar, the differentiation between two C-H bonds and the selective functionalization of only one of them remain a key challenge. Therefore, the available approaches are still unsatisfactory due to important limitations: low reactivity, limited scopes and selectivity issues.

In this proposal, a general approach to functionalize a CH bond located at a Far position (from a functional group) by Catalysis (FarCatCH) will be implemented with a special focus on underexplored transformations, affording important sulfur-and fluorine-containing compounds. Herein, I will develop new synthetic approaches for the remote functionalization of molecules based on i) a substrate-selectivity control and ii) the design of new catalysts using supramolecular tools. I will then iii) address a longstanding reactivity issue in organic synthesis: the trifluoromethylation of aliphatic compounds and apply the supramolecular catalysts for a remote enantioselective transformation.

Designing a full set of tools as Swiss army knife for the selective functionalization at unconventional positions inaccessible so far, can considerably change the way organic molecules are made. These original technologies will offer new synthetic routes to access original sulfur- and fluorine-containing molecules, compounds of interest in drugs discovery, material sciences, pharmaceutical and agrochemical industry.

Work performed

The FarCatCH project is organized in three independent work packages. During the first period from 1st January 2018 to 30th June 2019, the initial investigations were conducted on the WP1 and WP2. Indeed, significant advances were made regarding the substrate-selectivity control and the design of new catalysts using supramolecular tools. In general, the project followed the main lines proposed in the initial research program. As part of the progress we made, the design of efficient synthetic routes towards various classes of ligands was set up. Thus, a small library of ligands has been synthesized and is still growing. Besides initial tests for the remote functionalization of derivatives were carried out and intensive investigations are currently on-going. These preliminary results will be crucial for the next steps and the success of the next milestones in the project.
As a recognition of my expertise in the C-H bond activation research field, I was involved in the writing of a review providing an overview on directing groups in transition metal catalyzed C-H functionalization reactions (Chem. Soc. Rev. 2018, 47, 6603). Besides, the design of new reagents to achieve original sulfur-and fluorine-containing compounds was investigated. This work led to the publication of the following article: Chem. Commun. 2019, DOI: 10.1039/C9CC01851D. In line with my interests in organofluorine chemistry and especially the design of original reagents to promote unprecedented transformations, closely related to the ERC project, I recently wrote a review. This latter highlights the recent advances made towards a promising fluorinated moiety and summarizes the newly- designed reagents and their applications for the synthesis of fluorinated molecules (Front. Chem. 2019, 7, 111. DOI: 10.3389/fchem.2019).
In the course of this first period, several conferences in research institutes in France and in the world (Europe, China, India) were given to disseminate the science we are developing and as an ERC laureate (For more details, please see: http://www.bessetgroup.cnrs.fr/). Moreover, eight conferences and one oral communication were given as an invited speaker in national (eg. RCOM10, Progress in Organofluorine Chemistry, SECO55â€¦) and international conferences (ICOC2018, 22th International Symposium on Fluorine Chemistry) amongst othersâ€¦.

The project publications are:

J. Wang, H.-Y. Xiong, E. Petit, L. Bailly, X. Pannecoucke, T. Poisson, T. Besset,
Chem. Commun. 2019, DOI: 10.1039/C9CC01851D.
BiCl3-Mediated direct functionalization of unsaturated Câ€“C bonds with an electrophilic SCF2PO(OEt)2 reagent

E. Carbonnel, T. Poisson, P. Jubault, X. Pannecoucke, T. Besset,
Front. Chem. 2019, 7, 111. DOI: 10.3389/fchem.2019.
Recent Advances for the Direct Introduction of the CF2Me Moiety.

C. Sambiagio, D. SchÃ¶nbauer, R. Blieck, T. Dao-Huy, G. Pototschnig, P. Schaaf, T. Wiesinger, M. F. Zia, J. Wencel-Delord, T. Besset, B. U. W. Maes, M. SchnÃ¼rch
Chem. Soc. Rev. 2018, 47, 6603.
A comprehensive overview of directing groups applied in metal catalysed Câ€“H functionalisation chemistry

Final results

The work achieved during this first report period provides the foundations to fulfill the original goals of the FarCatCH project. The expected results until the end of the project are in line with the ones initially envisioned. I believe that the current progress made since the beginning of this FarCatCH project will be helpful to achieve our high-gain objectives, initially scheduled. Hence, FarCatCH will impact the organic chemistry field by providing new and sustainable synthetic tools for the remote functionalization of derivatives. The original technologies will offer a general manifold to access a wide range of original sulfur- and fluorine-containing molecules, particularly interesting for pharmaceutical and agrochemical industry and material sciences. These tools are of interest for the late-stage functionalization of complex molecules in quest for new leads for drugs discovery.