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.

Design and Synthesis of Two Steroid-Pyrrolo-Triazecin Derivatives Using Estrone and Pregnenolone as Chemical Tools

“…The yield for 8 was 65 % and for 9 of72%. Similar 1 H NMR and 13 C NMR data for the compound 8 or 9 were obtained compared with method A.…”

“…It is important to mention that there are many procedures for the formation of amides which are known in the literature, for example the reaction of amine with trichloroisocyanuric acid 18 , NaH/DMF 19 , ZrOCl 2 20 , tetrabutyl ammonium bromide 21 . Analyzing these data and other report which indicate the preparation of amide groups with some carbodiimides 22 ; therefore, in this study 11 or 12 were reacted with succinic acid in presence of a carbodiimide derivative to form the compounds 13 …”

“…Infrared spectra (IR) were recorded using KBr pellets on a Perkin Elmer Lambda 40 spectrometer. 1 H and 13 C NMR (nuclear magnetic resonance) spectra were recorded on a Varian VXR-300/5 FT NMR spectrometer at 300 and 75.4 MHz (megahertz) in CDCl 3 (deuteratedchloform) using TMS (tetramethylsilane) as internal standard. EIMS (electron impact mass spectroscopy) spectra were obtained with a Finnigan Trace Gas Chromatography Polaris Q Spectrometer.…”

α,β-Unsaturated diimines as substrates in catalytic C–H activation reactions and as ligands in iron carbonyl complexes

“…It has been pointed out before, that the formation of pyrrolone derivatives works best if the substituents at the imine nitrogen atoms are aliphatic moieties [11]. Corresponding to this observation, the bis-dihydropyrrolone derivatives 8-10 are produced in yields of 90% (9) or >98% (8,10). Only in the reaction of 4 to produce 9 traces of a product in which the formation of the heterocycle took place only with one of the imine subunits are observed in the GC-MS investigations of the product mixture.…”

“…On the other hand, the same imine substrates are converted into c-lactams in the reaction with carbon monoxide and a-olefins catalyzed by Ru 3 (CO) 12 [8][9][10][11][12][13]. As a side product of this catalytic three component reactions 2,3-disubstituted pyrrole derivatives are observed [11].…”