Iron‐Catalyzed C−C and C−N Bond‐Forming Tandem Amidation Offering Access to 3‐Amino‐3‐Aminomethyl‐2‐Oxindole Frameworks

An iron‐catalyzed protocol for the synthesis of 3‐amino‐3‐aminomethyl‐2‐oxindole heterocyclic structures is disclosed employing isatins and non‐nucleophilic N ‐methoxybenzamides. This reaction class is associated with broad scope and tolerates numerous functionalities, such as fluoro, chloro, bromo, iodo, trifluoromethyl, nitrile, ester, ether, and alkenyl, including heteroaryl – thiophene, benzothiophene, carbazolyl, indolyl, eugenol, and polycyclic cholesterol moieties. Detailed mechanistic investigations reveal that the reaction proceeds via iron‐catalyzed N−O bond cleavage in N ‐methoxybenzamides, generating formaldehyde and benzamide, and through the intermediacy of isatin‐ketimines and N ‐(hydroxymethyl)benzamides. Overall, this amidation reaction involves one C−C and two C−N bond‐forming tandem processes, providing a range of β ‐amino‐aminomethyl‐oxindoles (45 examples) in up to 88% yields.