Stereoselective Construction of 22-Oxygenated Steroid Side Chains by Dimethylaluminum Chloride-Mediated Ene Reactions of Aldehydes

Article abstract of DOI:10.1021/jo00068a024

Dimethylaluminum chloride-mediated ene reactions of aldehydes with (Z)-3β-acetoxy-5,17(20)-pregnadiene (3) at low temperatures followed by acetylation of the resulting alcohols have been shown to produce stereoselectively 22-acetoxylated steroid derivatives in good to excellent yields.Interestingly, the stereochemical outcome of these ene reactions has been found to be dependent upon the size of the aldehyde employed; the less sterically demanding aldehydes such as 4-methylpentanal and cyclohexanecarboxaldehyde afford the (20α,22α)-22-acetoxy products (4a) stereoselectively, whereas the relatively congested aldehydes such as benzaldehyde and other aromatic aldehydes produce predominantly the (20α,22β)-22-acetates (4b).This novel stereochemical observation has been rationalized in terms of the relative stabilities of the two most plausible transition states where the difference in the relative bulk between the R group of the aldehyde RCHO and the Me2AlCl coordinating to the aldehyde oxygen in an anti-fashion seems to be manifested in the stereochemical outcome at C-22 of the ene products.