Synthesis of N-picolylcarboxamides via palladium-catalysed aminocarbonylation of iodobenzene and iodoalkenes

Abstract

A systematic investigation of the palladium-catalysed aminocarbonylation of iodobenzene, 1-iodocyclohexene and 1′-iodostyrene in the presence of N-nucleophiles containing pyridyl moieties (2-, 3- and 4-picolylamine, N-ethyl-4-picolylamine, di-(2-picolyl)amine) was carried out. The two types of iodo substrates differ substantially regarding the selectivity towards carbonylation: while the aminocarbonylation of iodobenzene resulted in the formation of carboxamide and ketocarboxamide mixtures under various conditions, with the predominant formation of ketocarboxamide even at low carbon monoxide pressure, the aminocarbonylation of iodoalkenes under same conditions gave the corresponding unsaturated carboxamide exclusively. Most of the carboxamides and phenylglyoxylamides, obtained via single and double carbon monoxide insertion, respectively, were isolated in yields of synthetic interest (up to 86%). Low reaction rates and unexpected chemoselectivity towards carboxamide formation have been observed with di-(2-picolyl)amine as N-nucleophile in the aminocarbonylation of iodobenzene.