Perfluorinated tags and phases for synthesis

The development of more efficient, rapid and environmentally-friendly synthesis processes, whether for the production of high-tonnage compounds, pharmaceutical compounds or on a laboratory scale, represents a major objective of current research. Most research efforts are focused on optimizing the activity of existing reagents or catalysts, or discovering new reactions. However, in a synthesis process, the purification stage is not to be neglected, as the yield of isolated product and the overall energy cost of the synthesis are highly dependent on the nature and efficiency of the latter . Methodologies that enable catalysts, reagents or by-products to be easily separated or recycled from a reaction medium should be encouraged as part of a sustainable chemistry approach. Ideally, these methods should avoid as far as possible chromatographic purification, which consumes large quantities of organic solvents, and, if possible, distillation, which is energy-intensive and can lead to catalyst degradation. The use of liquid (perfluorocarbons) or solid (perfluorinated silicas or Teflon) perfluorinated phases is fully in line with this approach. Perfluorocarbons (PFCs), such as n-perfluorohexane (C ₆ F ₁₄ ), are liquids with extreme physico-chemical properties. They are chemically inert, non-toxic and are the most apolar liquids in existence. They are both hydrophobic and lipophobic, so at room temperature they form two-phase liquid/liquid systems with most organic solvents. The principle of fluorous chemistry is to increase the affinity of catalysts, reagents or substrates for liquid or solid perfluorinated phases, i.e. to increase their fluorophilicity. This is achieved by modifying catalysts, reagents or substrates with perfluoroalkyl moieties known as fluorinated tags (F-tags). As we shall see later, fluorinated compounds present in a reaction medium can then be easily separated from non-fluorinated products by liquid/liquid or solid/liquid separation techniques that are simple to implement, fast and efficient.