3,5-Disubstituted-1,2,4-oxadiazoles and 4,5-dihydro-3,5-disubstituted-1,2,4-oxadiazoles

A series of 3,5-disubstituted-1,2,4-oxadiazoles (2) were prepared from a mono- or dichlorophenyl-substituted amidoxime and (i) an acid chloride, (ii) an isatoic anhydride, or (iii) a β-keto ester. Although cyclizations of the same amidoximes with acetaldehyde gave 4,5-dihydro-5-methyl-substituted derivatives (5), that annulation procedure either failed or gave low yields with other aldehydes. A novel alternative method, the diborane reduction of 2, has been found to be a generally applicable procedure for preparing 5. The reduction is regioselective, i.e., only the 4,5-(C=N) linkage is reduced even when a large excess of diborane is present.