Synthetic Study of Dragmacidin E: Enantioselective Construction of the Seven-Membered Ring-Fused Indole Skeleton with Contiguous Stereocenters

We developed an enantioselective synthetic method of constructing a seven-membered ring-fused indole skeleton with contiguous stereocenters for the synthesis of dragmacidin E. Introduction of chirality at the benzylic position was achieved by Ir-catalyzed asymmetric hydrogenation. After construction of the tricyclic molecular framework using Pd-catalyzed cascade cyclization, the tetrasubstituted carbon center was created using the Ag nitrene-mediated C-H amination reaction. The developed method provided access to the functionalized seven-membered ring-fused indole skeleton with a hydroxymethyl branch in the tetrasubstituted carbon.

Automated summary

We developed an enantioselective synthetic method utilizing Ir-catalyzed asymmetric hydrogenation to introduce chirality at the benzylic position, followed by Pd-catalyzed cascade cyclization for tricyclic molecular framework construction and Ag nitrene-mediated C-H amination for tetrasubstituted carbon center creation. This method provides access to a functionalized seven-membered ring-fused indole skeleton with a hydroxymethyl branch in the tetrasubstituted carbon.