Synthesis of 2‐(1‐Phenylvinyl)benzofurans and 2‐(1‐Phenylvinyl)indoles as Antimitotic Agents by a Tandem Palladium‐Assisted Coupling‐Cyclization Reaction between 1‐Phenylvinyl Iodides and ortho ‐Substituted Arylalkynes

A series of functionalized 2‐(1‐phenylvinyl)benzofurans 2 and 2‐(1‐phenylvinyl)indoles 3 were prepared from 1‐phenylvinyl iodides and silylated alkynes in a one‐pot reaction. After a desilylation step, the Sonogashira coupling reaction between the resulting terminal alkynes and 1‐phenylvinyliodide derivatives 6 gave enyne intermediates, which underwent a 5‐ endo ‐ dig cyclization to afford 2‐(1‐phenylvinyl) heterocycles 2 and 3 in good yields. This method provides a rapid and efficient approach to build up benzoheterocycle‐based isocombretastatin A‐4 analogues of biological interest. From this series of compounds, the indoles 3o and 3r inhibited tubulin assembly at a micromolar level comparable to that of iso CA‐4.