Harnessing Quinone Methides: Total Synthesis of (±)-Vaticanol A

Although quinone methides are often postulated as intermediates in the biosynthesis of many polyphenolic natural products, deploying their power in a laboratory setting to achieve similar bond constructions has sometimes proven challenging. Herein, a total synthesis of the resveratrol trimer vaticanol A has been achieved through three instances of quinone methide chemistry. These operations, one of which succeeded only under very specific conditions, expediently generated its [7,5]‐carbocyclic core, afforded a unique sequence for dihydrobenzofuran formation, and concurrently generated, in addition to the target molecule, a series of diastereomers reflective of many other isolates. Three's Company: The resveratrol trimer vaticanol A, along with a number of diastereomeric congeners, has been synthesized for the first time through an effective strategy utilizing three reactive quinone methide intermediates to forge three critical bonds (highlighted in pink). These events, one of which succeeded only under very specific conditions, expediently generated its [7,5]‐carbocyclic core and afforded a unique sequence for dihydrobenzofuran formation.