STEREOSELECTIVE CONSTRUCTION OF 22-OXYGENATED STEROID SIDE-CHAINS BY DIMETHYLALUMINUM CHLORIDE-MEDIATED ENE REACTIONS OF ALDEHYDES

Dimethylaluminum chloride-mediated ene reactions of aldehydes with (Z)-3beta-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 (20alpha,22alpha)-22-acetoxy products (4a) stereoselectively, whereas the relatively congested aldehydes such as benzaldehyde and other aromatic aldehydes produce predominantly the (20alpha,22beta)-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.