Dyotropic Rearrangements of Fused Tricyclic β‑Lactones: Application to the Synthesis of (−)-Curcumanolide A and (−)-Curcumalactone

Dyotropic rearrangements of fused, tricyclic β-lactones
are
described that proceed via unprecedented stereospecific, 1,2-acyl
migrations delivering bridged, spiro-γ-butyrolactones. A unique
example of this dyotropic process involves a fused bis-lactone possessing
both β- and δ-lactone moieties which enabled rapid access
to the core structures of curcumanolide A and curcumalactone. Our
current mechanistic understanding of the latter dyotropic process,
based on computational studies, is also described. Other key transformations
in the described divergent syntheses of (−)-curcumanolide A
and (−)-curcumalactone from a common intermediate (11 and 12
steps from 2-methyl-1,3-cyclopentanedione, respectively), include
a catalytic, asymmetric nucleophile (Lewis base)-catalyzed aldol-lactonization
(NCAL) leading to a tricyclic β-lactone, a Baeyer–Villiger
oxidation in the presence of a β-lactone, and highly facial-selective
and stereocomplementary reductions of an intermediate spirocyclic
enoate. The described dyotropic rearrangements significantly alter
the topology of the starting tricyclic β-lactone, providing
access to complex spirocyclic cyclopentyl-γ-lactones and bis-γ-lactones
in a single synthetic operation.