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

• Published in: Tetrahedron Vol. 133; pp. 133292 - 133295
• Main Authors: Bede, Fanni, Mahó, Sándor, Sándor, Viktor, Mikle, Gábor, Kollár, László
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 03.03.2023; Elsevier
• Subjects: Carbon monoxide; Carbonylation; Chemistry; Chemistry, Organic; Cholane; Cholic acid; Palladium; Physical Sciences; Science & Technology; Carbonylation; Palladium; Cholic acid; Carbon monoxide; Cholane; PALLADIUM-CATALYZED CARBONYLATION; ARYL
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2023.133292

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. [Display omitted] •A novel synthetic route to obtain steroids functionalised in un-favoured position-7.•Functional group tolerance in palladium-catalysed aminocarbonylation of iodoalkenes.•Efficient synthesis of 7-carboxamidocholanes based on easily available starting material.