Diastereoselective Construction of 6,8-Dioxabicyclo[3.2.1]octane Frameworks from Vinylethylene Carbonates via Palladium-Organo Relay Catalysis

The 6,8-dioxabicyclo­[3.2.1]­octane (6,8-DOBCO) architecture widely exists in a broad spectrum of bioactive natural products, and the development of efficient and convenient protocols to construct this skeleton remains a challenging task. Here, we report a concise synthetic strategy for the single-step construction of 6,8-DOBCO frameworks from simple vinylethylene carbonates and amine-substituted enones. This protocol features a sequential reaction of N-allylic substitution, Diels–Alder cyclization, and intramolecular ketalization, which is promoted by metal-organo relay catalysis involving palladium/phosphoric acid or palladium/halogen-bonding catalytic system. Over 50 examples of 6,8-DOBCO derivatives with structural diversity have been facilely achieved with satisfactory synthetic results, including high levels of stereoselectivity, reasonable isolated yield, ample scope in reaction partners, high step economy, and operational simplicity.