Catalytic Hydroxycyclopropanol Ring-Opening Carbonylative Lactonization to Fused Bicyclic Lactones

A novel palladium-catalyzed ring
opening carbonylative lactonization
of readily available hydroxycyclopropanols was developed to efficiently
synthesize tetrahydrofuran (THF) or tetrahydropyran (THP)-fused bicyclic
γ-lactones, two privileged scaffolds often found in natural
products. The reaction features mild reaction conditions, good functional
group tolerability, and scalability. Its application was demonstrated
in a short total synthesis of (±)-paeonilide. The fused bicyclic
γ-lactone products can be easily diversified to other medicinally
important scaffolds, which further broadens the application of this
new carbonylation method.