Transition Metal-Free O-, N- and S-Arylations with Diaryliodonium Salts

Abstract: This thesis concerns the development of metal-free arylation procedures using diaryliodonium salts, a non-toxic and versatile electrophilic arylating reagent, with applications to synthesize biologically relevant targets.The first part describes a transition metal-free formal synthesis of phenoxazine with an O-functionalization of a certain phenol as a key step. Using a designed, unsymmetrical diaryliodonium salt, O-arylation provided an ortho-disubstituted diaryl ether which was cyclized to acetyl phenoxazine. An unusually stable iodine(III) intermediate was observed by NMR which could be converted to the product upon heating or applying a longer reaction time. This finding has an impact on the general understanding of ligand coupling mechanism which diaryliodonium salts follow.The second and third part describes arylation of nitrogen nucleophiles. A general N-arylation of aliphatic amines under mild conditions was developed. The reaction has a broad substrate scope with a great variety in acyclic and cyclic primary and secondary amines, as well as diaryliodonium salts. The developed protocol is applicable for aryl transfer of both electron-poor and electron-rich aryl groups, the latter delivering products that had previously not been synthesized in a transition metal-free manner.The successful N-arylation methodology was subsequently broadened to allow N-arylation of amino acid derivatives, resulting in a more general method to access biologically interesting compounds in a metal-free fashion which has never been reported in combination with diaryliodonium salts. The reaction could transfer a variety of aryl groups without compromising the stereocenter of the amino acid ester.The last part describes the S-arylation of thioamides, resulting in the formation of thioimidates, a relatively unstudied class of compounds where the majority of the formed products are novel. Both electron-rich and electron-poor aryl groups could be transferred with high chemoselectivity and a large ortho-effect was observed. Furthermore, when examining this arylation procedure with cyclic thioamides, a different trend was observed and N-arylated thioamides were isolated.