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

Abstract

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.

A Scalable Biomimetic Synthesis of Resveratrol Dimers and Systematic Evaluation of their Antioxidant Activities

“…Although seemingly trivial, the use of alkylated resveratrol derivative 4 b proved to be crucial to the success of this strategy since it tempers the redox potential of the stilbene, prevents the formation of regioisomeric dimers or undesired oligomers, and improves substrate solubility in nonpolar solvents, an effect critical for product chemoselectivity. Furthermore, despite the lability generally associated with quinone methides,19 which are typically generated and reacted in situ,7c dimers 5 , 6 , and 8 were found to be bench stable and could be purified by flash chromatography. This stability proved instrumental in the tautomerization of 5 / 5′ to 8 under strongly basic conditions while maintaining “switchable” Friedel–Crafts reactivity under Lewis acidic conditions.…”

Synthesis of resveratrol tetramers via a stereoconvergent radical equilibrium

“…Although the synthetic community has presented several innovative approaches to the resveratrol dimers (4–10), access to higher–order oligomers remains a serious challenge. In 2011, Snyder and coworkers reported a de novo synthetic approach to this problem, accessing several higher–order oligomers through homologation of dimeric core structures (11), a strategy which has since been employed in two additional trimer syntheses (12, 13), and which represents the only successful strategy to date for the preparation of these compounds.…”

Iodine‐Mediated Direct Generation of o‐Quinone Methides at Room Temperature: A Facile Protocol for the Synthesis of ortho‐Hydroxybenzyl Thioethers

“…o-Quinonem ethides (o-QMs) are reactive, short-lived intermediate species typically utilized in organic synthesis [11a-d] and in drug discovery. [11e] They act as versatile key components in the synthesis of naturalp roducts [12] and in cycloaddition reactions. [13] Tailored o-QMs have served as DNA alkylators, and also function as ideal cross-linker probes.…”