A unique example of the one-pot trans-diastereoselective reaction of meso-tricyclic anhydrides is reported. The process involves anhydride ring opening by an amidoxime and the sequential cis- to trans- epimerization/cyclodehydration of the O-acylamidoxime intermediate. The resulted 1,2,4-oxadiazole/norborna(e)ne hybrids are obtained in moderate to good yields and > 95 % diastereomeric excess without any additional purifications. These compounds are interesting not only for drug discovery but for other chemistry-related fields due to the presence of two easily modifiable moieties.