<i>N</i>‑Methylimidazole Promotes the Reaction of Homophthalic Anhydride with Imines

The addition of <i>N</i>-methylimidazole (NMI) to the reaction of homophthalic anhydride with imines such as pyridine-3-carboxaldehyde-<i>N</i>-trifluoroethylimine (<b>9</b>) reduces the amount of elimination byproduct and improves the yield of the formal cycloadduct, tetrahydroisoquinolonic carboxylate <b>10</b>. Carboxanilides of such compounds are of interest as potential antimalarial agents. A mechanism that rationalizes the role of NMI is proposed, and a gram-scale procedure for the synthesis and resolution of <b>10</b> is also described.