Alkoxycarbonylpiperidines as N-nucleophiles in the palladium-catalyzed aminocarbonylation

Abstract

Piperidines possessing ester functionality, such as 2-(methoxycarbonyl)piperidine (methyl pipecolinate), 3-(ethoxycarbonyl)piperidine (ethyl nipecotate), and 4-(ethoxycarbonyl)piperidine (ethyl isonipecotate), were used as N-nucleophiles in palladium-catalyzed aminocarbonylation of iodobenzene and iodoalkenes such as 1-iodocyclohexene and 17-iodoandrost-16-ene. While the aminocarbonylation of both iodoalkenes, carried out under mild reaction conditions, resulted in the exclusive formation of the carboxamide, the same reaction of iodobenzene brought about the mixture of the corresponding carboxamide and 2-ketocarboxamide. The chemoselectivity toward the latter compounds, formed via double carbonyl insertion, was substantially increased by using high carbon monoxide pressure (up to 40 bar). Carboxamides derived from iodoalkenes and ketocarboxamides derived from iodoarene have been obtained in moderate to high yields.