Formal Synthesis of Gracilamine Using Rh(I)-Catalyzed [3 + 2 + 1] Cycloaddition of 1‑Yne–Vinylcyclopropanes and CO

Reported here is a formal synthesis of gracilamine using Rh­(I)-catalyzed [3 + 2 + 1] reaction of yne-VCP (±)-4 and CO. The key reaction gave the cycloadduct (±)-trans-3 with the A–B–C core structure of gracilamine. This advanced intermediate was further transformed to Gao’s intermediate (±)-2 via regular transformations to realize the formal synthesis of gracilamine. The present strategy was used to accomplish the asymmetric formal synthesis of gracilamine using chiral substrate (+)-4.