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

摘要

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 isoCA-4.