A simple approach to multifunctionalized N1-alkylated 7-amino-6-azaoxindole derivatives using their in situ stabilized tautomer form

Article abstract of DOI:10.1016/j.tet.2016.08.055

A simple approach for the synthesis of multifunctionalized N1-alkyl 7-amino-6-azaoxindole derivatives was developed and investigated. Formation of 5-amino- and 7-amino-6-aza-2-oxindoles 12a and 13a, respectively, was achieved using an intramolecular reductive cyclization as a key step. Subsequent alkylation of the pyrrole N1 atom in 12a led to the desired N1-alkylated compounds 22a–24 comprising different functionalities. Alkylation of 5-amino-substituted regioisomer 13a under the same conditions as used for 12a did not resulted in N1-alkylated products. To find a plausible explanation for the observed differences in reactivity, we investigated the possible tautomers of 12a and 13a and the distribution of their neutral and ionized forms in a gas phase. The relevant physicochemical properties of compounds 12a and 23 were determined.