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

• Published in: Advanced synthesis & catalysis Vol. 343; no. 8; pp. 795 - 801
• Main Authors: Imhof, Wolfgang, Berger, Daniel, Kötteritzsch, M., Rost, M., Schönecker, B.
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag GmbH 31.12.2001; Wiley‐VCH Verlag GmbH
• Subjects: activation; alkenes; diastereoselectivity; imines; ruthenium
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/1615-4169(20011231)343:8<795::AID-ADSC795>3.0.CO;2-M

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.