Photoredox catalytic activation of sulfur hexafluoride for the synthesis of pentafluorosulfanylated organic compounds

• Applicant: Professor Dr. Hans-Achim Wagenknecht
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 505932961

The incorporation of fluorinated substituents into organic molecules significantly affects their physical, chemical, biological and pharmaceutical properties. Accordingly, fluorinated compounds play an important role in pharmaceutical chemistry, in agrochemistry, in dye chemistry, and in material chemistry for optoelectronics. Among the fluorinated substituents, the pentafluorosulfanyl group is probably the most unexplored one, therefore often designated as “forgotten functional group”. Pentafluorosulfanylated compounds are prospective alternatives to other fluorinated compounds, thus the pentafluorosulfanyl group does not simply represent a more expensive perfluorinated group. So far, the exploration and the use of the pentafluorosulfanyl group in organic compounds are drastically limited by the difficult synthetic accessibility due to the toxicity of the available pentafluorosulfanylation reagents. Sulfur hexafluoride is an important alternative, but chemically completely inert. Thermal methods efficiently destruct sulfur hexafluoride, but cannot easily be applied for pentafluorosulfanylations. The overall goal of this project is to use sulfur hexafluoride as pentafluorosulfanylation reagent by means of advanced photoredox catalysis to synthesize valuable pentafluorosulfanylated organic compounds and building blocks. In the first two stages we plan to advancing N-phenylphenothiazines as well as N,N-diphenylphenazines as tunable organophotoredox catalysts, and the photoredox catalytic pentafluorosulfanylation of styrene derivatives with heterocyclic components. For the broader use of the pentafluorosulfanyl substituent in medicinal and material chemistry, an efficient and non-toxic preparation of aromatic pentafluorosulfanylated compounds is crucial. Accordingly, we plan to prepare pentafluorosulfanylated arenes from organic boronic acid esters and trifluoroborates that are activated in a photoredox catalytic approach and subsequently cleaved into carbon-centered radicals. Furthermore, we plan to extend this chemistry to dehydroalanine derivatives to synthesize pentafluorosulfanylated amino acids and peptides. The incorporation of pentafluorosulfanylated amino acids is important for a novel class of amino acids with altered properties and/or as fluorine NMR labels. Taken together, this project will significantly broaden the substrate scope of photoredox catalytic pentafluorosulfanylation and bring it to a level that these compounds can be considered for the chemistry disciplines (mentioned in the second sentence) in the future.

• DFG Programme: Research Grants
• International Connection: Switzerland
• Cooperation Partner: Dr. David Rombach