DEFIS

Decades of chemical research have shown that the fluorine atom and the fluorine-containing motifs profoundly impact the structure, reactivity and function of organic and inorganic molecules. Fluorine containing compounds are nowadays synthesized in pharmaceutical, agrochemical, polymer and electronic research on a routine basis. As an example, it is well established that fluorine atom(s) and/or fluoroalkyl group(s) can lead to many beneficial effects in a biologically active molecule. A logical consequence of these highly desirable properties is that more than 200 pharmaceuticals and 155 agrochemicals (among the 920 registered) containing at least one fluorine atom are currently on the market, which account for approximately 25% of the bioactive compounds. Material sciences are also deeply impacted by fluorine as exemplified by the annual growth rate of the fluoropolymer market estimated at 6.5% through 2016. In the past decade, Fluorine chemistry greatly expanded with insightful contributions from research groups aiming at developing novel synthetic methods and reagents for the regio- and stereoselective introduction of fluorine or fluorine-containing groups into molecular scaffolds. Indeed, the fluorine chemistry field is still developing at a rapid pace and one of the current challenges is the search for Emergent Fluorinated Substituents (EFS) that would not only give new reactivities and functions to man-made molecules but also eventually lead to improved biological activity or even a novel mode of action. Quite importantly, novel EFS would also avoid patent restrictions and thus provide an advantage over competitors in the field, a consideration of prime importance for the chemical industry. Such EFS are based on carbon (CHF2), linked to a heteroatom (O-CF3, S-CF3), or based on sulfur (SF5). From an industrial perspective, it should be noted that CHF2, OCF3 and SF5 groups are quite rarely encountered and there is an urgent need to develop academic as well as industrial viable approaches towards scaffolds substituted by these EFS. The project DEFIS belongs to "Challenge 3: Stimulate industrial renewal - Research focus 4: Sustainable chemistry, products, associated processes". In the DEFIS project, we have created a consortium of two partners gathering three teams, sharing common research interests but also possessing different specific expertises, which aims to investigate the synthesis and reactivity of three different types of emergent fluorinated substituents (CHF2, OCF3 and SF5) incorporated in a broad array of cyclic and acyclic chemical motifs. The proposal is organized in three objectives: in the first objective, we will develop an access to enantioenriched difluoromethylated compounds and in the second objective, we will focus on enantioenriched building blocks incorporating OCF3 and SF5 substituents. Finally, in the third objective, we will tackle the synthesis of SF5-substituted nitrogen heterocycles. The overall goals of the project have been defined to address the crucial challenges that lay ahead for the chemical industry in terms of innovation and intellectual property in the field of EFS, that will ultimately translate to numerous areas of our daily life, from life- to material sciences. Finally, a special attention has been paid to the management of the proposal in order to prevent dead ends and excessive delays in the realization of the different tasks.