Regioselective Arylation of Amidoaryne Precursors via Ag-Mediated Intramolecular Oxy-Argentation

An unprecedented silver-mediated intramolecular oxy-argentation of 3-amidoaryne precursors that quickly generates a heteroarylsilver species is developed. AgF acts as both a stoichiometric fluoride source and a reagent for the formation of a benzoxazolylsilver intermediate via aryne generation. Pd-catalyzed coupling reactions of (hetero)aryl iodides with a silver species, generated in situ, allow for the synthesis of various C7-arylated benzoxazoles. As a result, an aryl group is selectively introduced into the meta-position of 3-amidobenzyne precursors. Mechanistic studies have indicated the presence of a benzoxazolylsilver intermediate and revealed that the reaction proceeds via an intramolecular oxy-argentation process, which is initiated by a direct fluoride attack on the silyl group. Ag-mediated/Pd-catalyzed cross-coupling via intramolecular oxy-argentation of aryne to synthesize heterobiaryl compounds has first been realized. The newly developed method for subjecting a heteroarylsilver intermediate formed via aryne generation to coupling reactions opens up numerous opportunities to expand the scope of aryne chemistry. image