Synthesis of Fluorinated Amides Starting from Carbohydrates Based on the Claisen Rearrangement

The search for new methods for installation of fluorine atoms into organic molecules is still a widely studied issue. In this work, an efficient synthetic protocol for the synthesis of fluorine‐containing amides derived from sugar has been presented. This approach involved the Claisen rearrangement of previously obtained fluorinated vinyl ethers. The three fluorinated olefins: 1,1,3,3,3‐pentafluoroprop‐1‐ene (2H‐PFP), 1,2,3,3,3‐pentafluoroprop‐1‐ene (1H‐PFP) and hexafluoroprop‐1‐ene (HFP) were used as a source of fluorine. New compounds were characterized by 1H, 19F and 13C NMR spectroscopy and high resolution mass spectrometry. The X‐ray crystal structures of some fluorinated derivatives were obtained confirming structure, geometry and absolute configuration. The resulting molecules, due to possibility of further transformation of their functional groups, can be valuable fluorinated scaffolds for the synthesis of subsequent chemical compounds. The synthesis of a small library of α‐trifluoromethyl‐γ,δ‐unsaturated and α‐fluoro‐α‐trifluoromethyl‐γ,δ‐unsaturated carbonyl compounds based on the Claisen rearrangement is reported. Fluorinated olefins were used as building blocks supplying fluorine atoms. As a result, fluorinated esters and alcohols were also obtained. They are a valuable material for subsequent transformations. The methodology presented in this work could be applied to a wide range of compounds as a valuable tool to construct unnatural amino acids or peptidomimetics.