Synthesis of Condensed Tetrahydroisoquinoline Class of Alkaloids by Employing TfOH-Mediated Imide Carbonyl Activation

Isoquinoline-based polycyclic lactams such as isoindoloisoquinolinones, pyrroloisoquinolinones, and benzo[a]quinolizinones were successfully assembled from the corresponding imides by using a TfOH-mediated (TfOH = trifluoromethanesulfonic acid) imide carbonyl activation and cyclization strategy. By employing this simple method, the isoquinoline alkaloids crispine A, trolline/oleracein E, and erythrinarbine were successfully synthesized in racemic form. The reaction of unsymmetrical N-phenethylphthalimides with TfOH displayed excellent regioselectivity, which was rationalized by DFT calculations.