Investigation of a Late-Stage Derivatization Approach to Isatogens: Discovery of New Reaction Pathways

We have developed a new strategy for preparing 2-substituted indolone N-oxides (isatogens) by substitution reactions with aryl- and alkyl-organometallic reagents. This approach allows a range of substituents to be incorporated at a late stage and complements existing methods that necessitate their early stage incorporation during substrate preparation. Further chemistry has been found to take place at the nitrone moiety; intramolecular dipolar cycloaddition provides access to angularly fused tricyclic heterocycles. More unusually however, these compounds are prone to further addition by organozinc reagents leading to 2,2-disubstituted 3-oxindole products.