On the Copper-Promoted Backbone Arylation of Histidine-Containing Peptides Using Triarylbismuthines

We report herein our detailed investigation on the histidine-directed backbone arylation of histidine-containing peptides using triarylbismuth reagents. The reaction proceeds on the backbone NH of the amino acid that precedes the histidine, the so-called n-1 position. The protocol is applicable to dipeptides where the histidine is located at the C-terminus and to tripeptides where the histidine occupies the central position. The transformation is promoted by copper(II) acetate in the presence of phenanthroline (Phen) and diisopropylethylamine in dichloromethane at 50 degrees C under oxygen. An excellent scope was observed for the triarylbismuthines. In all cases, the imidazole ring of the histidine is protected with a trityl group to prevent the arylation of the side chain. An ATCUN-like model is proposed to explain the observed results.