Abstract
Calyciphylline F represents the final challenge in the total synthesis of the caged polycyclic-type of Daphniphyllum alkaloids due to the strained 8-azatricyclo[4.2.1.0(4,8)]nonane ring system. Here, we report the total synthesis of calyciphylline F. We construct the ring system by applying [4 + 3] cycloaddition reaction of pyrroles with 2-oxyallyl cations to an intramolecular reaction, followed by an intramolecular aldol reaction and capture of the resulting alkoxide as the xanthate. The bridgehead quaternary carbon center is constructed by the intramolecular addition reaction of the bridgehead radical to the alkoxy-acrylate, which is designed based on the proposed mechanism of by-product formation. Finally, another 6-exo-radical cyclization reaction constructs the last remaining ring and achieves the total synthesis of calyciphylline F.