Synthesis of 5,5,6-Fused Tricyclic Lactones: Stereocontrol of Three Consecutive Stereocenters

We report a new, highly diastereoselective method for the synthesis of strained 5,5,6-fused tricyclic γ-lactones via a palladium-catalyzed tandem Heck/Suzuki cross-coupling reaction, followed by epoxidation and lactone-forming epoxide opening. Using this sequence, we prepared tricyclic γ-lactones with three consecutive stereocenters from simple, readily available starting materials, including one derived from enantiomerically pure biomass-based levoglucosenone. Our method provides a stereocontrolled approach to complex scaffolds of potential relevance in synthetic and medicinal chemistry.