Competing Domino Knoevenagel-Cyclization Sequences with N-Arylcinnamylamines

Abstract

Domino Knoevenagel-cyclization reactions of Narylcinnamylamines were carried out with active methylene reagents, which took place with five competing cyclization mechanisms: intramolecular hetero Diels−Alder reaction, stepwise polar [2 + 2] cycloaddition, styryl or aza-Diels−Alder reactions followed by rearomatization, and [1,5]-hydride shift-6-endo cyclization. In the stepwise aza-Diels−Alder reaction, the Nvinylpyridinium moiety acted as an azadiene, producing a condensed heterocycle with tetrahydroquinolizinium and tetrahydroquiniline subunits. Antiproliferative activity with low micromolar IC 50 values was identified for some of the novel scaffolds.