Palladium-catalyzed diaminocarbonylation: synthesis of androstene dimers containing 3,3′- or 17,17′-dicarboxamide spacers

Abstract

Novel androstene-based dimers linked through A-and D-ring with 3,3 0 -and 17,17 0 -dicarboxamide spacers, were synthesized via palladium-catalyzed aminocarbonylation. Androstane derivatives possessing either 3-iodo-3,5-diene or 17-iodo-16-ene functionality were used as substrates in the presence of palladium-phosphine in situ catalysts and aliphatic and aromatic diamines as N-nucleophiles. Since androst-4-ene-3,17-dione was used as starting material, a multistep synthesis including protection/deprotection of one of the keto functionalities (3-one or 17-one) as ethylene ketals, transformation of the other keto group to iodoalkene functionality via its hydrazone, and palladium-catalyzed aminocarbonylation of the iodoalkene functionality was used. In this way, new dimeric compounds possessing a keto functionality were obtained in moderate-to-good isolated yields, via highly chemoselective reactions, under relatively mild conditions.

Selective Synthesis of N-Acylnortropane Derivatives in Palladium-Catalysed Aminocarbonylation

“…The amine nucleophiles (nortropinone ( a ) and nortropine ( b )) were purchased from TCI Chemicals and were used without further purification. 1-Iodocyclohexene ( 1 ) [ 73 ], 4- tert -butyl-1-iodocyclohexene ( 2 ) [ 73 ], 17-iodoandrost-16-ene ( 4 ) [ 74 ], and 2-iodobornene ( 5 ) were synthesized by the modified Barton-procedure [ 75 , 76 ]. The compound 6a is known, and the characterization data were in accordance with the literature.…”

A review on steroid dimers: 2011–2019

“…A number of bis-androstanes 88a-95a (32-42%) with 3,3'-dicarboxamide spacers were synthesized in a simple one-step reaction via palladium-catalyzed aminocarbonylation of 3iodo-17-ethylene ketal (87). The lower yields could be explained by the formation of the other minor dimers 88b-95b and 88c-95c due to isomerization of 3,5-diene to the corresponding 2,4diene (Scheme 23) [14].…”