A Unifying Bioinspired Synthesis of (−)-Asperaculin A and (−)-Penifulvin D

The first syntheses
of the isomeric dioxafenestrene natural products
(−)-asperaculin A and (−)-penifulvin D are reported.
Each target is formed selectively by choice of oxidant in a final
divergent bioinspired Baeyer–Villiger (BV) reaction. Density
functional theory calculations reveal that electrostatic interactions
between the oxidant leaving group and the lactone motif accounts for
a reversal of selectivity with H2O2/H3O+ compared to peracids. Synthetic features include forging
the polycyclic carbon framework with a diastereoselective meta-photocycloaddition biased by an ether substituent at
the aryl α-position. The encumbered tertiary alcohol was installed
by cyanation of a ketone intermediate followed by nonaqueous hydrolysis
of the resulting delicate cyanohydrin.