Collect. Czech. Chem. Commun. 2001, 66, 1777-1796

Novel Rearrangements of the 2-Chloroacrylonitrile Cycloadducts of Steroidal 14,16-Dien-17-yl Acetates

James R. Bull*, Richard S. Gordon and Claudia Grundler

Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa


Cycloaddition of 3-methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate (1) with 2-chloroacrylonitrile furnishes 17β-acetoxy-16α-chloro-3-methoxy-14,17α-ethenoestra-1,3,5(10)-triene-16β-carbonitrile (2) as the major product, which undergoes alkali-mediated rearrangement to (161R)-3-methoxy-17-oxo-16β,15β,14-(ethane[1,1,2]triyl)-14β-estra-1,3,5(10)-triene-161-carbonitrile (7). A similar reaction course is followed by the related 16-methyl derivative 4, and it is shown that minor 15-chloro-15-cyano cycloadducts 3 and 6 undergo Grob fragmentation. Functional group manipulations and regioselective bond-scission processes are described, for conversion of rearrangement product 7 into 16β,15β,14-(ethane[1,1,2]triyl) and cyclobuta[14β,15β] analogues of estradiol.

Keywords: [4 + 2]Cycloadditions; 2-Chloroacrylonitrile; Rearrangements; 19-Norsteroids; Estradiols; Steroids.

References: 26 live references.