The Stereoselective Ru3(CO)12-Catalyzed Synthesis of Steroidal 1,3-Dihydropyrrol-2-one Derivatives from α,β-Unsaturated Imines, Carbon Monoxide and Ethylene

Abstract

The reaction of α,β-unsaturated imines, derived from steroidal amines and cinnamaldehyde, with carbon monoxide and ethylene leads to the formation of steroids with a 1,3-dihydropyrrol-2-one ring system attached to the D-ring of the steroid. In addition, a new stereogenic center at C-3 of the pyrrolone ring is produced during the reaction sequence. In the case of a 16-position of the imine moiety the yields are nearly quantitative but the diastereoselectivity is low whereas the sterically more hindered 17-position shows a decreased reactivity but quite good diastereoselectivities. Complete diastereoselectivity is achieved if the starting compound exhibits an additional silyl ether group in the 17β-position besides the imine subunit in the 16β-position. The compound bearing the pyrrolone substituent at 17β-position was characterized by means of X-ray crystallography showing that the rotation of the pyrrolone ring is hindered by a strong intramolecular hydrogen bond between the carbonyl oxygen of the pyrrolone moiety and the hydrogen at C-17. The question of whether this intramolecular hydrogen bond is also responsible for the observed diastereoselectivities is discussed.