Systematic investigation on the synthesis of androstane-based 3-, 11- and 17-carboxamides via palladium-catalyzed aminocarbonylation.
3,17-Dicarboxamido-androst-3,5,16-triene, 3-carboxamido-androst-3,5-dien-17-one, 17-carboxamido-androst-4,16-dien-3-one and 11-carboxamido-androst-5,9(11)-dien-3,17-dione derivatives were synthesized in homogeneous carbonylation reactions from the corresponding 3,17-diiodo-androst-3,5,16-triene, 3-iodo-androst-3,5-diene-17-ethylene ketal, 17-iodo-androst-5,16-dien-3-ethylene ketal, 11-iodo-androst-5,9(11)-diene-3,17-bis(ethylene ketal) derivatives, respectively. A highly chemoselective palladium-catalyzed aminocarbonylation of the corresponding iodo-alkene, carried out under mild reaction conditions, can be considered as the key-step for the introduction of the carboxamide functionalities. The synthesis of the iodo-alkene substrate is based on the transformation of the corresponding keto derivative to hydrazone, which was treated with iodine in the presence of a base (1,1,3,3-tetramethyl guanidine). The aminocarbonylation reaction is highly tolerant towards the N-nucleophiles, i.e. various primary and secondary amines including amino acid methyl esters can also be used.
University of Pécs, Department of Inorganic Chemistry, Pécs, Hungary.
Péter
P
Acs
Attila
A
Takács
Mercédesz
M
Kiss
Noémi
N
Pálinkás
Sándor
S
Mahó
László
L
Kollár
D000577:Amides / Q000737:chemistry*; D000731:Androstanes / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D006146:Guanidines / Q000737:chemistry; D007454:Iodides / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*
D000577:Amides; D000731:Androstanes; D006146:Guanidines; D007454:Iodides; D010165:Palladium; C477069:1,1,3,3-tetramethylguanidine