A Biomimetic Approach for Construction of an Advanced Intermediate en Route to Melicolones A and B

A biomimetic approach for the synthesis of an advanced intermediate en route to melicolones A and B is described, leading to successful construction of the crucial bicyclo[3.2.1]octane carbon framework of these molecules. Key steps of the strategy include a Wolff rearrangement, a titanium-mediated Giese-type cyclization, and a nitrone acylation/rearrangement process. Our approach enables the reliable assembly of a fully functionalized tricyclic precursor, which in turn provides valuable handles for further elaboration of the target molecules.