Synthetic Study toward Daphnimacropodines

Abstract

Daphnimacropodines A-C are members of a small but structurally distinct subfamily of Daphniphyllum 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.