Synthetic Study toward Daphnimacropodines

Daphnimacropodines A-C are members of a small but structurally distinct subfamily of <i>Daphniphyllum</i> alkaloids. Their congested polycyclic skeletons, and two vicinal quaternary stereocenters, present significant synthetic challenges. This paper describes two stereoselective approaches to constructing the tricyclic core structures of daphnimacropodines, achieved through a straightforward Rh-catalyzed [4 + 3] cycloaddition using simple building blocks. This work also highlights an intramolecular Heck reaction that rapidly assembles the cyclohexane ring moiety, a Tsuji-Trost allylation that forged the critical C-8 quaternary stereocenter, an efficient hetero-Diels-Alder reaction, and an intramolecular nucleophilic addition, which paved the way to the key cyclopentane ring. The assembly of the tetrahydropyrrole motif was also investigated.