Total Synthesis and Structure Revision of (±)-Clavilactone D Through Selective Cyclization of an α,β-Dicarbonyl Peroxide

The
structure of (±)-clavilactone D was revised, and the synthesis
was achieved in seven steps from a substituted benzaldehyde. The key
step was the base-catalyzed cyclization of an α,β-carbonyl
peroxide, which was obtained by an iron-catalyzed three-component
reaction of a benzaldehyde, an alkene, and TBHP. NaBH4-mediated
reductive lactonization of the resulting cis-dicarbonyl
epoxide led to the α,β-epoxy-γ-butyrolactone skeleton
highly stereoselectively. The synthesis provides a concise, reliable,
and practical route to the revised structure of clavilactone D.