One-Pot Synthesis of N-Substituted Isoindolin-1-ones via Reductive Amination/Lactamization of Methyl 2-Formylbenzoate

An efficient, one-pot synthesis of N-substituted isoindolin-1-ones by an aminative reduction/lactamisation sequence of methyl 2-formylbenzoate is introduced. The reaction process includes aminative reduction of o-phthalaldehydic acid methylesters with primary aryl or alkyl amines using NaBH3CN and the following intramolecular nucleophilic N-attack on carbonyl carbon atom. For 4-substituted aromatic amines, alkyl amines and o-methylaniline, the transformation can be successfully completed in 1,2-dichloroethane at room temperature. For other 2-substituted aromatic amines, reflux in acetonitrile for 8 h in the presence of K2CO3 (2 equiv.) is needed. The reaction scopes were quite broad and up to 96% yield of diverse products was achieved.