Homogeneous catalytic hydrogenation of steroidal dehydroamino acid esters

Steroidal dehydroamino acid methyl esters (methyl α-acetamino-β-(cholesta-3,5-dien-3-yl) acrylate (1), methyl α-acetamino-β-(pregna-3,5-dien-3-yl)acrylate (2), methyl α-acetamino-β-(3-methoxy-estra-1,3,5,(10), 16-tetraene-17-yl)acrylate (3), methyl α-acetamino-β-(3β-acetoxy-androsta-16-en-17-yl)acrylate (4), methyl α-acetamino-β-(3β-benzoyloxy-androsta-16-en-17-yl)acrylate (5)) have been hydrogenated to the corresponding α-amino acid methyl esters in the presence of rhodium-phosphine in situ catalysts. The hydrogenation is highly chemoselective in case of 3,5-dienes. Reduction takes place exclusively in the side-chain. On the other hand, both olefinic double bonds were saturated when the 17-(methyl acetamidoacrylate) moiety was bonded to steroids possessingΔ16. Although the diastereoselectivity of hydrogenation is mainly determined by the steroid skeleton itself in the case of substrates possessing the acetamidoacrylate moiety in position-17, the ratio of epimers can be modified by the structure of the tertiary phosphine ligand varied systematically in rhodium-phosphine in situ catalysts. The highest diastereoselectivity (75/25) was obtained when estra-1,3,5-triene derivative was used as substrate in the presence of achiral rhodium-triphenylphosphine catalyst. The stereochemistry of hydrogenation resulting in new stereogenic centers is discussed on the base of NMR investigations.