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

有机分子中引入含氟取代基会显著影响其物理、化学、生物和药学性质。因此，氟化化合物在药物化学、农业化学、染料化学和光电子材料化学中发挥重要作用。在氟化取代基中，五氟硫基可能是最未开发的一个，因此通常被称为“被遗忘的官能团”。五氟硫烷基化化合物是其他氟化化合物的预期替代物，因此五氟硫烷基基团并不仅仅代表更昂贵的全氟化基团。到目前为止，五氟硫烷基在有机化合物中的探索和使用受到由于可用的五氟硫烷基化试剂的毒性而难以合成的限制。六氟化硫是一种重要的替代品，但化学性质完全惰性。热方法有效地破坏六氟化硫，但不能容易地应用于五氟硫烷基化。本项目的总体目标是利用先进的光氧化还原催化技术，以六氟化硫为五氟硫烷基化试剂，合成有价值的五氟硫烷基化有机化合物和结构单元。在前两个阶段，我们计划推进N-苯基吩噻嗪以及N，N-二苯基吩嗪作为可调的有机光氧化还原催化剂，和光氧化还原催化苯乙烯衍生物的五氟硫烷基化与杂环组分。为了在医药和材料化学中更广泛地使用五氟硫烷基取代基，芳香族五氟硫烷基化化合物的有效且无毒的制备是至关重要的。因此，我们计划从有机硼酸酯和三氟硼酸酯制备五氟硫烷基化芳烃，这些有机硼酸酯和三氟硼酸酯在光氧化还原催化方法中被活化，随后裂解成碳中心自由基。此外，我们计划将这种化学方法扩展到脱氢丙氨酸衍生物，以合成五氟硫烷基化氨基酸和肽。五氟硫烷基化氨基酸的掺入对于具有改变的性质的新型氨基酸和/或作为氟NMR标记是重要的。总之，该项目将显着拓宽光氧化还原催化五氟硫烷基化的底物范围，并使其达到一个水平，这些化合物可以考虑在未来的化学学科（在第二句话中提到）。

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.