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 b y acetylation of the resulting alcohols have been shown to produce ste reoselectively 22-acetoxylated steroid derivatives in good to excellen t yields. Interestingly, the stereochemical outcome of these ene react ions has been found to be dependent upon the size of the aldehyde empl oyed; the less sterically demanding aldehydes such as 4-methylpentanal and cyclohexanecarboxaldehyde afford the (20alpha,22alpha)-22-acetoxy products (4a) stereoselectively, whereas the relatively congested ald ehydes such as benzaldehyde and other aromatic aldehydes produce predo minantly the (20alpha,22beta)-22-acetates (4b). This novel stereochemi cal observation has been rationalized in terms of the relative stabili ties 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 t o be manifested in the stereochemical outcome at C-22 of the ene produ cts.