Ta. Houston et al., STEREOSELECTIVE CONSTRUCTION OF 22-OXYGENATED STEROID SIDE-CHAINS BY DIMETHYLALUMINUM CHLORIDE-MEDIATED ENE REACTIONS OF ALDEHYDES, Journal of organic chemistry, 58(16), 1993, pp. 4287-4292
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.