Transition-metal-free C–N and C–C formation: synthesis of benzo[4,5]imidazo[1,2-a]pyridines and 2-pyridones from ynones

Abstract

Herein, a transition metal-free and efficient cascade reaction of ynones with 2-methylbenzimidazoles under mild conditions has been revealed. This cascade reaction involved a Michael addition/intramolecular cycloaddition/dehydration and provided the desired benzo[4,5]imidazo[1,2-a]pyridines in moderate to good yield. Furthermore, three benzo[4,5]imidazo[1,2-a]pyridines (3d, 3i, and 3q) exhibited good activities against Hep-G2 (human liver cancer), T-24 (human bladder cancer cell), and SK-OV-3 (human ovarian cancer) cell lines with IC₅₀ values in the range of 8.05–10.67 μmol L⁻¹. To investigate the mechanism of the effective inhibition of cell growth, further studies, including cell cycle analysis, apoptosis ratio detection, measurement of Ca²⁺ generation, ROS, mitochondrial membrane potential assay, and caspase-3/9 activation, were carried out on compound 3i.