Relaunching the power of fluorine

DuPont 2015 Chemistry Student Award winner Sébastien Alazet talks fluorine and how to reinvigorate a whole branch of chemistry…

The fluorine atom is one of the most powerful atoms in the periodic table. Because of its specific properties – electronegativity, hydrophobicity and polarity – fluorine brings a crucial physico-chemical modification to molecules. Since isolation of fluorine (F₂) by Henri Moissan in 1886, fluorinated compounds have been involved in various fields – medicine, crop protection, smart materials and many others.

Fluorine atoms are everywhere in your life. Development of new reagents and methods to introduce fluorinated moieties onto molecules has been a big challenge for chemists since the beginning of fluorine chemistry. I am a PhD student in the lab of Dr Billard at the University of Lyon in France which specialises in organofluorine chemistry. Mixing perfluoroalkyl chains and sulphur confers to these new groups impressive properties.

Among these new groups, SCF₃ stands out because of its high lipophilicity. Such a property could significantly modify the physico-chemical behaviours of compounds. For example, drugs could have increased permeation through cell membranes – for example the blood-brain barrier – and, thus, the bioavailability of the active molecules can be modulated. In spite of this interesting physical property, only a few industrial applications have been developed. Until now, among fluorine industrial applications, not many products incorporating trifluomethylthioether have become available on the market.

During the eighties, chemists used instable, aggressive and toxic reagents to introduce this SCF₃ group onto simple molecules. No major new methodologies emerged for many years. In 2010, we assisted to the “rebirth” of SCF₃ chemistry. This new hot topic aims to provide new methods to introduce the SCF₃ moiety.

Our objective was to propose to non-specialised chemists in fluorine chemistry new efficient tools. We have designed efficient and easy-to-handle reagents able to introduce the SCF₃ moiety onto molecules, namely trifluoromethanesulfenamides or Billard’s reagents. The challenge was this: Every chemist, even students, should be able to synthetise and use our reagents in their laboratory without specific expertise. We wanted to develop methodologies to produce interesting fluorinated molecules. The idea was to understand what chemists from various fields need and to propose solutions.

We can imagine a lot of industrial applications that open up pathways to more sustainable chemistry or facilitate production of interesting active products. These methodologies have the potential to increase the importance of fluorinated molecules.

CF₃S-aromatics and CF₃S-heterocyclic compounds can have a lot of applications in medicinal and agrochemistry. Fluorinated building blocks represent the base from which we can synthesise more elaborate molecules. Analogues of natural products are well known in drug discovery. To incorporate a trifluoromethylthioether on precursors of natural products was one of our objectives, as fluorinated analogues can have distinct biologic metabolism for drug discovery. Smart materials play an important part in our life. Proposing efficient architectures with new fluorinated monomers will be important in the future research projects.