An Asymmetric Pathway to Dendrobine by a Transition‐Metal‐Catalyzed Cascade Process

An asymmetric pathway to the caged tetracyclic pyrrolidine alkaloid, dendrobine, is reported. The successful synthetic strategy features a one‐pot, sequential palladium‐catalyzed enyne cycloisomerization and rhodium‐catalyzed diene‐assisted pyrrolidine formation by allylic CH activation. The developed transition‐metal‐catalyzed cascade process permits rapid access to the dendrobine core structure and circumvents the handling of labile intermediates. An intramolecular aldol condensation under carefully defined reaction conditions takes place with a concomitant detosylation, followed by reductive amine methylation, to afford a late‐stage intermediate (previously identified by several prior dendrobine syntheses) in only 10 synthetic steps overall. An asymmetric pathway to polycyclic alkaloid dendrobine was developed comprising a one‐pot palladium‐catalyzed enyne cycloisomerization, and rhodium‐catalyzed diene‐assisted pyrrolidine formation by allylic CH activation. Intramolecular aldol condensation with concomitant detosylation, followed by reductive amination, afforded an advanced intermediate in only 10 synthetic steps.