Synthesis of p-phenylene-based chiral dicarboxamides via aminocarbonylation of 1’,4-diiodostyrene

Abstract

Chiral p-phenylene-based dicarboxamides featuring carboxamide and 2-arylacrylamide motifs were synthesised through a synthetic sequence involving conventional organic reactions followed by palladium-catalysed aminocarbonylation. 4-Iodoacetophenone was used as starting material to prepare to 1’,4-diiodostyrene, which underwent several aminocarbonylation reactions, using in situ formed palladium-phosphine catalysts and various biologically relevant amines as N-nucleophiles such as, amino acid esters, nortropine, and aminoandrostane derivatives. By exploring the remarkable difference in reactivity between the iodoalkene and iodoarene functionalities, the aminocarbonylation of the iodoalkene moiety was carried first with high chemoselectivity, followed by sequential transformation of the iodoarene functionality into the corresponding carboxamide using a different nucleophile. This approach allowed us to obtain a range of otherwise challenging chiral dicarboxamides, in moderate to high isolated yields through highly chemoselective reactions.