Synthesis and reactivity of aryl iodo difluorides

Abstract

Organofluorine substrates are molecules of increasing demand in both academic and industrial settings. Organofluorine compounds are very rare in nature and therefore several approaches to their synthesis have been developed. In the work performed during this research tenure, the approach towards the synthesis of organofluorine substrates is based on the use of hypervalent iodine reagents. The structure of the research program can be summarized into three main sections: Synthesis of aryl iodo difluorides; Reactivity of aryl iodo difluorides towards organoselenium substrates; Approach toward stereoselective fluorinations with the synthesis of chiral iodo difluorides. Aryl iodo difluorides reagents have been known for more than a century but they have not been extensively used mainly due to their difficulty of synthesis, which require harmful and hazardous reagents. We have developed an alternative method for their preparation involving three synthetic steps: perborate oxidation of an aryl iodide, followed by basic hydrolysis and subsequent treatment with hydrofluoric acid. A number of aryl iodo difluorides were synthesized using this procedure and each of them is characterized by high purity and high yield. The reactivity of (difluoroiodo)toluene (DFIT) as a fluorinating agent was tested on organoselenium substrates. a-Seleno esters, amide and nitriles undergo a-fluorination when treated with 2 equivalents of DFIT. Under these conditions, the monofluoro derivatives were obtained with yields ranging from 20% to 65%. Additionally, (difluoroiodo)toluene can be employed in oxidative fluorinations. The exploitation of its oxidative nature produced tetraethyl ammonium iodo difluoride, and preliminary results indicate that it can be used as fluorinating agent, as well. The third aspect of the research dealt with stereoselective fluorination reactions. The synthesis of an opportune chiral iodo difluoride can provide the further development of hypervalent iodine reagents as fluorinating reagents. Different substrates were used to reach this goal and the study conducted in this direction brought about the synthesis of a difluoride with the iodine atom in oxidation state V, which can be use as chiral fluorine transfer after a simple modification of its structure