Arylation Reactions Using Diaryliodonium Salts

Abstract

Diaryliodonium salts have been widely used in organic chemistry, in particular as oxidizing agents and more recently as arylation reagents. The work presented in this thesis considers both the metal-free and copper catalysed processes for N-, O-arylation and fluorination using diaryliodonium salts, in particular how the control and selectivity of the transformation is influenced by the nature of various substitution patterns and typical reaction conditions. During this study, a range of diaryliodonium salts with different substituent patterns and counter-ions have been synthesized in order to determine their chemical and physical properties and the resultant selectivity of the arylation process as this variation of functionality allows exploration of the impact of both steric and electronic factors. A novel diaryliodonium copper complex was discovered. By using DSC-TGA analysis, the thermal decomposition of different diaryliodonium salts has been determined. Some decompose rather than melt at these temperatures suggesting limits on the temperatures that may be employed in their subsequent reactions. This study has also shown that when the arylation reaction is conducted metal-free (i.e. without a catalyst), the selectivity of fluorination and both N- and O-arylation is mostly determined by the electronic nature of the relevant groups (the most electron-deficient arene is transferred) whereas when the reaction was conducted in the presence of a copper catalyst, the selectivity was mostly influenced by extreme steric factors (the least hindered arene was transferred) although electronic control was still evident but to a lesser extent. According to introducing a fluorous target into diaryliodonium salts and using F-SPE method, product and by-products could be easily separated. In summary, it was found that: ⚫ A range of diaryliodonium salts could be readily prepared using a range of synthetic methods. ⚫ The thermal stability of diaryliodonium salts was affected by the choice of counter-ion. ⚫ When the reaction was conducted under copper catalysis good selectivity (transfer of the v least hindered arene) could be achieved for fluorination and both N- and O-arylation reactions ⚫ A novel diaryliodonium copper complex was discovered having a unique iodine (III) copper interaction. ⚫ A range of fluorous diaryliodonium salts have been prepared and in association with F-SPE enabled rapid separation of the desired arylated product from the arene by-products and any unreacted diaryliodonium salt.