Diastereodivergent Access to cis,cis- and cis,trans-Angular Triquinanes: Total Synthesis of (±)-Arnicenone

Description

Chia-Hao Liu and six colleagues forge a forked road into angular triquinanes, natural product frameworks of three fused five-membered rings bent at an angle and crowded with stereocenters. Synthetic chemists prize these compact terpenoid skeletons but struggle to set their many handedness centers on demand.

From shared allene starting materials, two complementary cyclizations diverge. A Lewis acid route assembles one fusion pattern through a ring-forming annulation, while a light-driven cycloaddition followed by oxidative ring expansion delivers the mirror arrangement. A single substituent swap on the starting allene flipped the annulation's selectivity outright, granting direct access to the other family. Calculations traced the divergence to the first ring-closing step, where crowding decides the outcome. The team proved the platform by completing a total synthesis of the natural product arnicenone through the photochemical branch, with a second route confirming the strategies complement each other.

Catalog record

Source: https://europepmc.org/article/MED/PMC13651531