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.