Carboxamide formation in less favoured positions: Facile synthesis of 7-carboxamidochenodeoxycholanic acid derivatives

Abstract

The sterically highly un-favoured position-7 of a steroidal skeleton was functionalised in a reaction sequence of conventional synthetic reactions and palladium-catalysed aminocarbonylation. The synthesis was based on the use of chenodeoxycholanic acid as starting material, which was transformed to 24-carboxamide, followed by oxidation of 7-hydroxy group. The resulting 7-oxo functionality was converted to the corresponding iodoalkene by the Barton's method. The 7-iodo-6-ene functionality underwent high-yielding aminocarbonylation in the presence of palladium-phosphine in situ catalysts and various amines as N-nucleophiles. The new 7-carboxamido compounds were obtained in good isolated yields, via highly chemoselective reactions, under relatively mild conditions.