Diastereoselective aminocarbonylation of a steroidal iodoalkene with 2,2′-diamino-1,1′-binaphthalene in palladium-catalysed reactions

A palladium-catalysed aminocarbonylation of a steroidal iodoalkene (17-iodo-5α-androst-16-ene) model compound with 2,2′-diamino-1,1′-binaphthalene as an N-nucleophile was carried out. The combination of a steroidal skeleton possessing central elements of chirality and a binaphthyl moiety with axial chirality was carried out resulting in a novel type of steroidal carboxamides. The binaphthalene—steroid conjugates are potential 5α-reductase inhibitors. Both epimers of the monocarboxamide and those of the dicarboxamide, formed with moderate diastereoselectivity, were isolated and fully characterised.

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(Rax,10S,13S)-17-(N-(2′-Amino-[1,1′-binaphthalen]-2′-yl)-10,13-dimethyl-2,3,4,5,6,7,8,9,10,11,12,13,14,15-tetradecahydro-1H-cyclopenta[a]-phenanthrene-17-carboxamideC40H44N2O[α]D20 = +191.5 (c 0.914, CHCl3)Source of chirality: diastereoselective aminocarbonylationAbsolute configuration: (Rax,10S,13S)

(Sax,10S,13S)-17-(N-(2′-Amino-[1,1′-binaphthalen]-2′-yl)-10,13-dimethyl-2,3,4,5,6,7,8,9,10,11,12,13,14,15-tetradecahydro-1H-cyclopenta[a]-phenanthrene-17-carboxamideC40H44N2O[α]D20 = −37.1 (c 1.34, CHCl3)Source of chirality: diastereoselective aminocarbonylationAbsolute configuration: (Sax,10S,13S)

(Rax,10S,10′S,13S,13′S)-N,N′-([1,1′-Binaphthalene]-2,2′-diyl)bis(10,13-dimethyl-2,3,4,5,6,7,8,9,10,11,12,13,14,15-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-carboxamide)C60H72N2O2[α]D20 = +25.7 (c 0.389, CHCl3)Source of chirality: diastereoselective aminocarbonylationAbsolute configuration: (Rax,10S,10′S,13S,13′S)

(Sax,10S,10′S,13S,13′S)-N,N′-([1,1′-Binaphthalene]-2,2′-diyl)bis(10,13-dimethyl-2,3,4,5,6,7,8,9,10,11,12,13,14,15-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-carboxamide)C60H72N2O2[α]D20 = +12.0 (c 0.418, CHCl3)Source of chirality: diastereoselective aminocarbonylationAbsolute configuration: (Sax,10S,10′S,13S,13′S)