Biomimetic, Multigram, and Enantioselective Total Synthesis of the Microtubule Destabilizing Pterocarpan (6a S ,11a S )-2,3,9-Trimethoxy-6a,11a-dihydro-6 H -benzofuro[3,2- c ]chromene

A four-step (three-pot) and biomimetic total synthesis of the title compound (+)-1, a pterocarpan-type natural product and microtubule destabilizing agent, was achieved using readily available starting materials. The tetramethoxy-substituted isoflavone 17 was prepared (via ketone 16) from these and on treatment with AlCl3 and sodium iodide this underwent regioselective mono-demethylation to give congener 20. This was subjected to asymmetric transfer hydrogenation (ATH) and then an acidic workup. By such means the title pterocarpan (+)-1 was obtained in multigram quantities and >99% ee.