Facile Generation of ortho-Quinodimethanes Toward Polycy-clic Compounds

The Diels–Alder reaction is a cornerstone of organic synthesis, enabling the construction of complex molecular archi-tectures through the cycloaddition of a diene and a dienophile. Among the various dienes employed in this reaction, ortho-quinodimethane stands out as an exceptionally powerful intermediate due to its high reactivity, making it par-ticularly effective for constructing benzo-fused polycyclic skeletons found in biologically important molecules such as natural products and pharmaceuticals. [1–3] Although this method has been widely applied in total synthesis,[4–7] the requirement for the laborious preparation of its precursors remains a significant challenge. This study presents a so-lution through a conceptually distinct palladium-catalyzed generation of ortho-quinodimethane via a multicompo-nent assembly reaction of readily available chemicals, specifically 2-vinylbromoarenes, diazo species, and carbon nucleophiles bearing a dienophile moiety. This approach leads to the synthesis of a diverse range of polycyclic com-pounds. The key to the present methodology is the unlocking of unprecedented reactivity in a benzyl–palladium in-termediate,[8,9] which facilitates distal C–C bond formation on the vinyl group. The synthetic applications of this ortho-quinodimethane generation method are demonstrated through the synthesis of a range of polycyclic compounds, in-cluding a natural product, highlighting the convergent and diversity-generating nature of this reaction.